Fingolimod versus interferon beta 1-a: Benefit-harm assessment approach based on TRANSFORMS individual patient data

BACKGROUND Fingolimod is a disease-modifying drug approved for multiple sclerosis but its benefit-harm balance has never been assessed compared to other active treatments. OBJECTIVES Our aim was to compare the benefits and harms of fingolimod with interferon beta-1a using individual patient data from TRial Assessing injectable interferon versus FTY720 Oral in RRMS trial. METHODS We modelled the health status of patients over time including Expanded Disability Status Scale measurements, relapses and any adverse events. We assessed the mean health status between arms and the proportion of patients whose health deteriorated or improved relatively to baseline, using a prespecified minimal important difference of 4.6. We performed sensitivity analyses to test our assumptions. RESULTS Main and sensitivity analyses favoured fingolimod 0.5 mg over interferon beta-1a. The average health status difference was 1.01 (95% CI 0.93-1.08). Patients on fingolimod 0.5 mg were 0.47 (95% CI: 0.35-0.63, p < 0.001) times less likely to experience a relevant decline in health status compared to interferon beta-1a patients, with a number needed to treat of 7.10 [5.18, 11.23]. CONCLUSIONS Fingolimod's net benefit over interferon beta-1a did not reach the clinical relevance over 1 year, but the decreased risk for health status deterioration may be more pronounced more long term and patients may prefer less treatment burden associated with fingolimod

On the Hiatus in the Acceleration of Tropical Upwelling Since the Beginning of the 21st Century

Chemistry-climate models predict an acceleration of the upwelling branch of the Brewer-Dobson circulation as a consequence of increasing global surface temperatures, resulting from elevated levels of atmospheric greenhouse gases. The observed decrease of ozone in the tropical lower stratosphere during the last decades of the 20th century is consistent with the anticipated acceleration of upwelling. However, more recent satellite observations of ozone reveal that this decrease has unexpectedly stopped in the first decade of the 21st century, challenging the implicit assumption of a continuous acceleration of tropical upwelling. In this study we use three decades of chemistry transport-model simulations (1980-2013) to investigate this phenomenon and resolve this apparent contradiction. Our model reproduces the observed tropical lower stratosphere ozone record, showing a significant decrease in the early period followed by a statistically robust trend-change after 2002. We demonstrate that this trend-change is correlated with corresponding changes in the vertical transport and conclude that a hiatus in the acceleration of tropical upwelling occurred during the last decade

Association of physical activity with adiposity in preschoolers using different clinical adiposity measures: a cross-sectional study.

More research is needed about the association between physical activity (PA), sedentary behaviour (SB), and adiposity in preschoolers, particularly using more direct clinical measures of adiposity. Therefore, the main objective of this study was to investigate the association between objectively measured PA and different clinical adiposity measures in a large sample of preschoolers. Four hundred sixty-three predominantly normal-weight (77%) 2-6-year-old preschool children participated in the Swiss Preschoolers' Health Study (SPLASHY). Physical activity was measured using accelerometers and was analyzed using 15-s (uni-axial) epoch length using validated cut-offs. Adiposity measures included body mass index (BMI), the sum of four skinfolds, and waist circumference (WC). Multilevel linear regression modeling, adjusted for age, sex and wear time, was used to assess the association between PA and SB with BMI, WC, and skinfold thickness. Total PA and different PA intensities were positively and SB was inversely associated with BMI in the total sample and in the normal-weight children (p &lt; 0.05). Total PA was inversely associated with skinfold thickness in overweight and obese children (p &lt; 0.05), while there was only a weak association for vigorous PA (p &gt; 0.05). Moderate and moderate-to-vigorous PA were positively, and SB was negatively associated with WC in the total sample and in the normal-weight children (p &lt; 0.05). Additional adjustment for potential sociocultural and biological confounding variables attenuated some of the results. In this very young and predominantly normal-weight population, PA is positively related to BMI and WC, but this relationship is not observed in overweight and obese children. In this latter population, PA is inversely, and SB is positively related to skinfold thickness. Skinfold thickness could represent a useful and simple clinical measure of body fat in preschoolers. The role of vigorous PA in the prevention of early childhood obesity should be further investigated in future studies. ISRCTN ISRCTN41045021 . Retrospectively registered 06 May 2014

Mental health of individuals infected with SARS-CoV-2 during mandated isolation and compliance with recommendations-A population-based cohort study

BACKGROUND: Isolation is an indispensable measure to contain the SARS-CoV-2 virus, but it may have a negative impact on mental health and overall wellbeing. Evidence on the isolation experience, facilitating and complicating factors is needed to mitigate negative effects. METHODS AND FINDINGS: This observational, population-based cohort study enrolled 1547 adults from the general population with SARS-CoV-2 infection reported to authorities between 27 February 2020 and 19 January 2021 in Zurich, Switzerland. We assessed the proportion of individuals reporting symptoms of depression and anxiety before, during and after isolation (by DASS-21), and queried worries, positive experiences, and difficulties. We analyzed the association of these outcomes with socio-demographics using ordinal regression. Additionally, we report free-text statements by participants to capture most important aspects of isolation. The proportion of participants affected by depression or anxiety increased during isolation from 10·0% to 17·1% and 9·1% to 17·6%, respectively. Ordinal regression showed that taking care of children increased the difficulty of isolation (OR 2·10, CI 1·43-3·08) and risk of non-compliance (OR 1·63, CI 1·05-2·53), especially in younger participants. A facilitating factor that individuals commonly expressed was receiving more support during isolation. CONCLUSION: Isolation due to SARS-CoV-2 presents a mental burden, especially for younger individuals and those taking care of children. Public health authorities need to train personnel and draw from community-based resources to provide targeted support, information, and guidance to individuals during isolation. Such efforts could alleviate the negative impact isolation has on the mental and physical health of individuals and ensure compliance of the population with recommendations

Natural course of post COVID-19 condition and implications for trial design and outcome selection: A population-based longitudinal cohort study

Background Evidence from population-based studies on the longer-term natural course of post COVID-19 condition is limited, but crucial for informing patients and healthcare providers and for effectively designing clinical trials. Objectives To evaluate longer-term symptoms and health outcomes within a cohort of SARS-CoV-2 infected individuals. Design Population-based, longitudinal cohort. Setting General population, Canton of Zurich, Switzerland. Patients 1543 adults with confirmed SARS-CoV-2 infection and 628 adults without infection. Measurements Changes in self-reported health status over time, factors associated with persistence of non-recovery, and prevalence and excess risk of symptoms at 6 and 12 months post-infection compared to non-infected individuals. Results 25% of SARS-CoV-2 infected individuals did not recover by 6 months. Of those, 67% and 58% also did not recover at 12 and 18 months after infection, respectively. Hospitalization for acute COVID-19, pre-existing fatigue and pain or discomfort, and presence of specific systemic, cardiovascular, or musculoskeletal symptoms at 6 months were associated with persistent non-recovery. Symptom prevalence was higher among infected individuals compared to non-infected individuals at 6 months (adjusted risk difference (aRD)=17%) and 12 months (aRD=20%). aRDs for individual symptoms ranged from 2% to 12%, with the highest excess risks observed for altered taste or smell, post-exertional malaise, fatigue, and reduced concentration and memory. Limitations We relied on self-reported assessments and did not assess the effects of vaccination or infection with emerging variants of concern. Conclusion These findings emphasize the need for effective interventions to reduce the burden of post COVID-19 condition. They further demonstrate the importance of using multiple outcome measures and of considering the expected rates of natural recovery and heterogenous patient trajectories in the design and interpretation of clinical trials

Individual-Level Evaluation of the Exposure Notification Cascade in the SwissCovid Digital Proximity Tracing App: Observational Study

Background: Digital proximity tracing (DPT) aims to complement manual contact tracing (MCT) in identifying exposed contacts and preventing further transmission of SARS-CoV-2 in the population. Although several DPT apps, including SwissCovid, have shown to have promising effects on mitigating the pandemic, several challenges have impeded them from fully achieving the desired results. A key question now relates to how the effectiveness of DPT can be improved, which requires a better understanding of factors influencing its processes. Objective: In this study, we aim to provide a detailed examination of the exposure notification (EN) cascade and to evaluate potential contextual influences for successful receipt of an EN and subsequent actions taken by cases and contacts in different exposure settings. Methods: We used data from 285 pairs of SARS-CoV-2-infected cases and their contacts within an observational cohort study of cases and contacts identified by MCT and enrolled between August 6, 2020, and January 17, 2021, in the canton of Zurich, Switzerland. We surveyed participants with electronic questionnaires. Data were summarized descriptively and stratified by exposure setting. Results: We found that only 79 (58.5%) of 135 contacts using the SwissCovid app whose corresponding cases reported to have triggered the EN also received one. Of these, 18 (22.8%) received the EN before MCT. Compared to those receiving an EN after MCT (61/79, 77.2%), we observed that a higher proportion of contacts receiving an EN before MCT were exposed in nonhousehold settings (11/18, 61.1%, vs 34/61, 55.7%) and their corresponding cases had more frequently reported mild-to-moderate symptoms (14/18, 77.8%, vs 42/61, 68.9%). Of the 18 contacts receiving an EN before MCT, 14 (77.8%) took recommended measures: 12 (66.7%) were tested for SARS-CoV-2, and 7 (38.9%) called the SwissCovid Infoline. In nonhousehold settings, the proportion of contacts taking preventive actions after receiving an EN was higher compared to same-household settings (82%, vs 67%). In addition, 1 (9%) of 11 ENs received in the nonhousehold setting before MCT led to the identification of a SARS-CoV-2-infected case by prompting the contact to get tested. This corresponds to 1 in 85 exposures of a contact to a case in a nonhousehold setting, in which both were app users and the case triggered the EN. Conclusions: Our descriptive evaluation of the DPT notification cascade provides further evidence that DPT is an important complementary tool in pandemic mitigation, especially in nonhousehold exposure settings. However, the effect of DPT apps can only be exerted if code generation processes are efficient and exposed contacts are willing to undertake preventive actions. This highlights the need to focus efforts on keeping barriers to efficient code generation as low as possible and promoting not only app adoption but also compliance with the recommended measures upon an EN. Trial registration: International Standard Randomised Controlled Trial Number Registry 14990068; https://doi.org/10.1186/ISRCTN14990068. Keywords: COVID-19; SARS-CoV-2; SwissCovid; app; contact tracing; digital proximity tracing; epidemiology; evaluation; exposure; mHealth; mobile app; notification; observational; public health; surveillance; tracking

Emotional eating is related with temperament but not with stress biomarkers in preschool children.

Emotional eating (EE) corresponds to a change in eating behavior in response to distress and results in an increase of food intake (overeating (EOE)) or in food avoidance (undereating (EUE)). EE has been related to temperament (i.e. negative emotionality) and dysregulated stress biomarkers in school-aged children; parenting has been understood to influence this relationship in older children. The aim of the study was to investigate to which extent stress biomarkers and negative emotionality are related to EE and to understand the role of parenting in this relationship. The sample consisted of 271 children aged 2-6 years of the Swiss cohort study SPLASHY. We assessed the child's EE, negative emotionality and parenting by parent based reports. Salivary samples were collected over two days to analyze cortisol and salivary alpha-amylase levels. From the whole sample of children, 1.1% showed EOE and 32.9% EUE. Negative emotionality was related to EOE and EUE (0.13 (CI 0.06, 021), p &lt; 0.001; 0.25 (CI 0.14, 0.35), p &lt; 0.001). There was no relationship between stress biomarkers and EE and parenting had any moderating role (all p &gt; 0.05). Similar to a Danish study, parents reported more often EUE than EOE of their child. Both are related to the temperament. Even though the course of EE has not yet been well documented, we conclude that a certain subgroup of children with difficult temperament could be at-risk for eat and weight regulation problems in later childhood