Evidence-based coaching of core competencies in epidemiology, using the framework of randomized controlled trials: the Zurich approach.

Teaching epidemiological concepts in academic settings poses a challenge due to the intricate nature of the discipline as both a science and a practice. Whereas traditional classroom-based teaching methods are commonly employed, evidence suggests they may not be the most effective approach for fostering core competencies and skills required in real-life scientific work. In this article, we describe our process of transitioning from traditional classroom teaching of epidemiology towards practice-based coaching to convey epidemiological concepts to bachelor's and master's students in Biomedicine. We chose the framework of randomized controlled trials (RCT) since they offer a great opportunity to teach epidemiological concepts in a hands-on course. This practice-based course encompasses the entire life cycle of a study, allowing students to design and conduct a short-term experiment, analyse its data and prepare a scientific paper. We provide a comprehensive overview of the course structure, content, learning objectives and course evaluation, while also discussing the advantages and disadvantages of this innovative format. Our approach offers a promising alternative to classroom teaching by incorporating practical, hands-on experiences offering students a high level of independence and self-determination, as well as facilitation and coaching by faculty. It has the potential to be applied across diverse academic settings, providing students with valuable skills and competencies in epidemiology.

A combined cross-sectional analysis and case-control study evaluating tick-borne encephalitis vaccination coverage, disease and vaccine effectiveness in children and adolescents, Switzerland, 2005 to 2022.

BackgroundTick-borne encephalitis (TBE) is a severe, vaccine-preventable viral infection of the central nervous system. Symptoms are generally milder in children and adolescents than in adults, though severe disease does occur. A better understanding of the disease burden and duration of vaccine-mediated protection is important for vaccination recommendations.AimTo estimate TBE vaccination coverage, disease severity and vaccine effectiveness (VE) among individuals aged 0-17 years in Switzerland.MethodsVaccination coverage between 2005 and 2022 was estimated using the Swiss National Vaccination Coverage Survey (SNVCS), a nationwide, repeated cross-sectional study assessing vaccine uptake. Incidence and severity of TBE between 2005 and 2022 were determined using data from the Swiss disease surveillance system and VE was calculated using a case-control analysis, matching TBE cases with SNVCS controls.ResultsOver the study period, vaccination coverage increased substantially, from 4.8% (95% confidence interval (CI): 4.1-5.5%) to 50.1% (95% CI: 48.3-52.0%). Reported clinical symptoms in TBE cases were similar irrespective of age. Neurological involvement was less likely in incompletely (1-2 doses) and completely (≥ 3 doses) vaccinated cases compared with unvaccinated ones. For incomplete vaccination, VE was 66.2% (95% CI: 42.3-80.2), whereas VE for complete vaccination was 90.8% (95% CI: 87.7-96.4). Vaccine effectiveness remained high, 83.9% (95% CI: 69.0-91.7) up to 10 years since last vaccination.ConclusionsEven children younger than 5 years can experience severe TBE. Incomplete and complete vaccination protect against neurological manifestations of the disease. Complete vaccination offers durable protection up to 10 years against TBE.

Exploring the Major Barriers to Physical Activity in Persons With Multiple Sclerosis: Observational Longitudinal Study.

BACKGROUND: Physical activity (PA) represents a low-cost and readily available means of mitigating multiple sclerosis (MS) symptoms and alleviating the disease course. Nevertheless, persons with MS engage in lower levels of PA than the general population. OBJECTIVE: This study aims to enhance the understanding of the barriers to PA engagement in persons with MS and to evaluate the applicability of the Barriers to Health Promoting Activities for Disabled Persons (BHADP) scale for assessing barriers to PA in persons with MS, by comparing the BHADP score with self-reported outcomes of fatigue, depression, self-efficacy, and health-related quality of life, as well as sensor-measured PA. METHODS: Study participants (n=45; median age 46, IQR 40-51 years; median Expanded Disability Status Scale score 4.5, IQR 3.5-6) were recruited among persons with MS attending inpatient neurorehabilitation. They wore a Fitbit Inspire HR (Fitbit Inc) throughout their stay at the rehabilitation clinic (phase 1; 2-4 wk) and for the 4 following weeks at home (phase 2; 4 wk). Sensor-based step counts and cumulative minutes in moderate to vigorous PA were computed for the last 7 days at the clinic and at home. On the basis of PA during the last 7 end-of-study days, we grouped the study participants as active (≥10,000 steps/d) and less active (<10,000 steps/d) to explore PA barriers compared with PA level. PA barriers were repeatedly assessed through the BHADP scale. We described the relevance of the 18 barriers of the BHADP scale assessed at the end of the study and quantified their correlations with the Spearman correlation test. We evaluated the associations of the BHADP score with end-of-study reported outcomes of fatigue, depression, self-efficacy, and health-related quality of life with multivariable regression models. We performed separate regression analyses to examine the association of the BHADP score with different sensor-measured outcomes of PA. RESULTS: The less active group reported higher scores for the BHADP items Feeling what I do doesn't help, No one to help me, and Lack of support from family/friends. The BHADP items Not interested in PA and Impairment were positively correlated. The BHADP score was positively associated with measures of fatigue and depression and negatively associated with self-efficacy and health-related quality of life. The BHADP score showed an inverse relationship with the level of PA measured but not when dichotomized according to the recommended PA level thresholds. CONCLUSIONS: The BHADP scale is a valid and well-adapted tool for persons with MS because it reflects common MS symptoms such as fatigue and depression, as well as self-efficacy and health-related quality of life. Moreover, decreases in PA levels are often related to increases in specific barriers in the lives of persons with MS and should hence be addressed jointly in health care management.

Better tools for better estimates: improving approaches to handling missing data in Swiss cancer registries.

OBJECTIVE: Various approaches have been used in the literature to handle missing vital status data in cancer registries. We aimed to compare these approaches to determine which led to the least biased estimates in typical analytic tasks of cancer registries. METHODS: A simulation study was performed using data from the Swiss National Agency for Cancer Registration for six tumor types. First, 5%, 10% and 15% missingness in the vital status were introduced artificially in the complete data. Second, missing vital status data were handled by applying no, single or multiple imputations. Five-year overall survival estimates, relative survival or standardized incidence ratio were computed. Estimates were compared with the true value. RESULTS: Standardized incidence ratio estimates for colorectal cancer obtained with multiple imputation yielded least biased results (-0.06 to -0.04), but the widest confidence intervals. Single imputation was more biased (-0.32) than using no imputation at all (-0.21). A similar pattern was observed for overall survival and relative survival. CONCLUSION: This simulation study indicated that often used single imputation (sometimes referred to as simulating follow-up times) techniques to fill in missing vital status data are likely too biased to be useful in practice. Multiple imputation approaches yielded standardized incidence ratio, overall and relative survival estimates with the least bias, indicating reasonable performance that is likely to generalize to other settings.

Experts vs. machine - comparison of machine learning to expert-informed prediction of outcome after major liver surgery.

BACKGROUND: Machine learning (ML) has been successfully implemented for classification tasks (e.g., cancer diagnosis). ML performance for more challenging predictions is largely unexplored. This study's objective was to compare machine learning vs. expert-informed predictions for surgical outcome in patients undergoing major liver surgery. METHODS: Single tertiary center data on preoperative parameters and postoperative complications for elective hepatic surgery patients were included (2008-2021). Expert-informed prediction models were established on 14 parameters identified by two expert liver surgeons to impact on postoperative outcome. ML models used all available preoperative patient variables (n = 62). Model performance was compared for predicting 3-month postoperative overall morbidity. Temporal validation and additional analysis in major liver resection patients were conducted. RESULTS: 889 patients included. Expert-informed models showed low average bias (2-5 CCI points) with high over/underprediction. ML models performed similarly: average prediction 5-10 points higher than observed CCI values with high variability (95% CI -30 to 50). No performance improvement for major liver surgery patients. CONCLUSION: No clinical relevance in the application of ML for predicting postoperative overall morbidity was found. Despite being a novel hype, ML has the potential for application in clinical practice. However, at this stage it does not replace established approaches of prediction modelling.

Determinants of health-related quality of life in healthy children and adolescents during the COVID-19 pandemic: Results from a prospective longitudinal cohort study.

Understanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological, and social factors in a large longitudinal population-based sample. Data was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort study Ciao Corona in Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc.), psychological (sadness, anxiousness, stress), and social (nationality, parents' education, etc.) factors, were assessed in 2020 and 2021 and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level. Median KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness, and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions, or nationality, were determinants only in individual subscales. CONCLUSION: Recent mental health, more than biological, physical, or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group. WHAT IS KNOWN: • Assessing health-related quality of life (HRQOL) in children and adolescents aids in understanding how life circumstances impact their well-being. • HRQOL is a complex construct, involving biological, psychological, and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples. WHAT IS NEW: • Mental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors. • Public health strategies to improve mental health may be effective in improving HRQOL in children.

Prescriptions of antidepressants and anxiolytics in France 2012-2022 and changes with the COVID-19 pandemic: interrupted time series analysis.

BACKGROUND: Depression and anxiety have increased in prevalence since the start of the COVID-19 pandemic. OBJECTIVE: To evaluate the consumption of antidepressants and anxiolytics from 2012 to 2022 and the pandemic's potential impact in France. METHODS: We conducted an interrupted time series analysis of routine drug sales data (Medic'AM) from all French outpatient pharmacies from 2012 to 2022. We investigated trends in defined daily doses of antidepressants and anxiolytics sold per 1000 inhabitants (DDD/TID) and related expenditures before and after pandemic onset and in relation with stringency of pandemic mitigation measures. Analyses were performed descriptively and using segmented linear regression, autoregressive and autoregressive integrated moving average models. FINDINGS: From 2012 to 2019, overall monthly antidepressant sales increased (+0.02 DDD/TID) while monthly anxiolytic sales decreased (-0.07 DDD/TID). With pandemic onset, there was a relevant and persisting trend increase (+0.20 DDD/TID per month) for antidepressant sales overall, with an estimated excess of 112.6 DDD/TID sold from May 2020 until December 2022. Anxiolytic sales were elevated from February 2020 throughout the pandemic but returned to expected levels by December 2022, with an estimated excess of 33.8 DDD/TID. There was no evident association between stringency and antidepressant or anxiolytic sales. CONCLUSIONS: This study showed a protracted trend increase in the consumption of antidepressants since pandemic onset, while increases in anxiolytic consumption were temporary. CLINICAL IMPLICATIONS: We provide evidence that the COVID-19 pandemic may have had long-lasting consequences on the prevalence and treatment of depression and anxiety disorders, requiring further actions by researchers and policy-makers to address this potential public mental health crisis.

Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection.

Numerous clinical parameters link to severe coronavirus disease 2019, but factors that prevent symptomatic disease remain unknown. We investigated the impact of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and endemic human coronavirus (HCoV) antibody responses on symptoms in a longitudinal children cohort (n = 2,917) and a cross-sectional cohort including children and adults (n = 882), all first exposed to SARS-CoV-2 (March 2020 to March 2021) in Switzerland. Saliva (n = 4,993) and plasma (n = 7,486) antibody reactivity to the four HCoVs (subunit S1 [S1]) and SARS-CoV-2 (S1, receptor binding domain, subunit S2 [S2], nucleocapsid protein) was determined along with neutralizing activity against SARS-CoV-2 Wuhan, Alpha, Delta, and Omicron (BA.2) in a subset of individuals. Inferred recent SARS-CoV-2 infection was associated with a strong correlation between mucosal and systemic SARS-CoV-2 anti-spike responses. Individuals with pre-existing HCoV-S1 reactivity exhibited significantly higher antibody responses to SARS-CoV-2 in both plasma (IgG regression coefficients = 0.20, 95% CI = [0.09, 0.32], P < 0.001) and saliva (IgG regression coefficient = 0.60, 95% CI = [0.088, 1.11], P = 0.025). Saliva neutralization activity was modest but surprisingly broad, retaining activity against Wuhan (median NT50 = 32.0, 1Q-3Q = [16.4, 50.2]), Alpha (median NT50 = 34.9, 1Q-3Q = [26.0, 46.6]), and Delta (median NT50 = 28.0, 1Q-3Q = [19.9, 41.7]). In line with a rapid mucosal defense triggered by cross-reactive HCoV immunity, asymptomatic individuals presented with higher pre-existing HCoV-S1 activity in plasma (IgG HKU1, odds ratio [OR] = 0.53, 95% CI = [0.29,0.97], P = 0.038) and saliva (total HCoV, OR = 0.55, 95% CI = [0.33, 0.91], P = 0.019) and higher SARS-CoV-2 reactivity in saliva (IgG S2 fold change = 1.26, 95% CI = [1.03, 1.54], P = 0.030). By investigating the systemic and mucosal immune responses to SARS-CoV-2 and HCoVs in a population without prior exposure to SARS-CoV-2 or vaccination, we identified specific antibody reactivities associated with lack of symptom development.IMPORTANCEKnowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020-2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.

Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study.

Understanding the development of humoral immune responses of children and adolescents to SARS-CoV-2 is essential for designing effective public health measures. Here we examine the changes of humoral immune response in school-aged children and adolescents during the COVID-19 pandemic (June 2020 to July 2022), with a specific interest in the Omicron variant (beginning of 2022). In our study "Ciao Corona", we assess in each of the five testing rounds between 1874 and 2500 children and adolescents from 55 schools in the canton of Zurich with a particular focus on a longitudinal cohort (n=751). By July 2022, 96.9% (95% credible interval 95.3-98.1%) of children and adolescents have SARS-CoV-2 anti-spike IgG (S-IgG) antibodies. Those with hybrid immunity or vaccination have higher S-IgG titres and stronger neutralising responses against Wildtype, Delta and Omicron BA.1 variants compared to those infected but unvaccinated. S-IgG persist over 18 months in 93% of children and adolescents. During the study period one adolescent was hospitalised for less than 24 hours possibly related to an acute SARS-CoV-2 infection. These findings show that the Omicron wave and the rollout of vaccines boosted S-IgG titres and neutralising capacity. Trial registration number: NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717 .

Health-Related Quality of Life and Adherence to Physical Activity and Screen Time Recommendations in Schoolchildren: Longitudinal Cohort Ciao Corona.

Objectives: We investigated changes in adherence to physical activity (PA) and screen time (ST) recommendations of children and adolescents throughout the pandemic, and their association with health-related quality of life (HRQOL). Methods: 1,769 primary (PS, grades 1-6) and secondary (SS, 7-9) school children from Ciao Corona, a school-based cohort study in Zurich, Switzerland, with five questionnaires 2020-2022. HRQOL was assessed using the KINDL questionnaire. PA (≥60 min/day moderate-to-vigorous PA) and ST (≤2 h/day ST) recommendations followed WHO guidelines. Results: Adherence to PA recommendations dropped in 2020 (83%-59% PS, 77%-52% SS), but returned to pre-pandemic levels by 2022 (79%, 66%). Fewer children met ST recommendations in 2020 (74% PS, 29% SS) and 2021 (82%, 37%) than pre-pandemic (95%, 68%). HRQOL decreased 3 points between 2020 and 2022, and was 9.7 points higher (95% CI 3.0-16.3) in March 2021 in children who met both versus no recommendations. Conclusion: Adherence to WHO guidelines on PA and ST during the pandemic had a consistent association with HRQOL despite longitudinal changes in behavior.

Surgical outcome improvement by shared decision-making: value of a preoperative multidisciplinary target clinic for the elderly in colorectal surgery.

PURPOSE: Frailty and comorbidities increase the risk of postoperative complications and raise treatment costs. Perioperative optimisation is shown to improve surgical outcomes for the elderly. The aim of this study was to assess the impact of introducing a multidisciplinary preoperative clinic for older patients (Colchester Older Persons' Evaluation for Surgery (COPES) clinic) undergoing major colorectal surgery. METHODS: This 5-year single centre study included patients >65 years with ≥3 comorbidities undergoing major colorectal surgery. From October 2018, patients with these characteristics were evaluated and optimised in the COPES clinic by a geriatrician and an anaesthetist. Outcomes were compared to high-risk patients operated on prior to COPES (pre-COPES group). The primary outcomes were postoperative morbidity at discharge and 6 months measured by the Comprehensive Complication Index. Patients were matched on age and number of comorbidities. RESULTS: A total of 54 patients were enrolled in the pre-COPES and 18 in the COPES group. After matching, the results were comparable for both groups. The length of stay was shorter in the COPES group and the recurrence rate was higher; however, it did not reach statistical significance in both findings. CONCLUSION: This clinic intends to improve treatment quality, placing emphasis on shared decision-making. More focus should be put on patient-reported outcomes and experiences. Especially for elderly patients, quality of life and maintaining independence are often their priority. To determine the true value of a preoperative multidisciplinary clinic targeting elderly comorbid patients, a prospective study with larger cohort is needed, focusing not only on objective outcomes but also on patient-reported outcomes.

Post COVID-19 condition, work ability and occupational changes in a population-based cohort.

Background: Evidence on the impact of post COVID-19 condition (PCC) on work ability is limited but critical due to its high prevalence among working-age individuals. This study aimed to evaluate the association between PCC, work ability, and occupational changes in a population-based cohort. Methods: We used data from working-age adults included in a prospective, longitudinal cohort of a random sample of all individuals infected with SARS-CoV-2 between August 2020 and January 2021 in the Canton of Zurich, Switzerland. We evaluated current work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), and PCC-related occupational changes one year after infection. Findings: Of 672 individuals included in this study, 120 (17.9%) were categorised as having PCC (defined as presence of self-reported COVID-19 related symptoms) at 12 months. There was very strong evidence that current work ability scores were mean 0.62 (95% CI 0.30-0.95) points lower among those with PCC compared to those without in adjusted regression analyses. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (adjusted odds ratio (aOR) 0.30, 95% CI 0.20-0.46) and mental (aOR 0.40, 0.27-0.62) demands in individuals with PCC. Higher age and history of psychiatric diagnosis were associated with more substantial reductions in current work ability. 5.8% of those with PCC reported direct effects of PCC on their occupational situation, with 1.6% of those with PCC completely dropping out of the workforce. Interpretation: These findings highlight the need for providing support and interdisciplinary interventions to individuals affected by PCC to help them maintain or regain their work ability and productivity. Funding: Federal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland; Horizon Europe.

There is no evidence that carbon dioxide-enriched oxygen before apnea affects the time to arterial desaturation, but it might improve cerebral oxygenation in anesthetized obese patients: a single-blinded randomized crossover trial.

PURPOSE: Carbon dioxide (CO2) increases cerebral perfusion. The effect of CO2 on apnea tolerance, such as after anesthesia induction, is unknown. This study aimed to assess if cerebral apnea tolerance can be improved in obese patients under general anesthesia when comparing O2/Air (95%O2) to O2/CO2 (95%O2/5%CO2). METHODS: In this single-center, single-blinded, randomized crossover trial, 30 patients 18-65 years, with body mass index > 35 kg/m2, requiring general anesthesia for bariatric surgery, underwent two apneas that were preceded by ventilation with either O2/Air or O2/CO2 in random order. After anesthesia induction, intubation, and ventilation with O2/Air or O2/CO2 for 10 min, apnea was performed until the cerebral tissue oxygenation index (TOI) dropped by a relative 20% from baseline (primary endpoint) or oxygen saturation (SpO2) reached 80% (safety abortion criterion). The intervention was then repeated with the second substance. RESULTS: The safety criterion was reached in all patients before cerebral TOI decreased by 20%. The time until SpO2 dropped to 80% was similar in the two groups (+ 6 s with O2/CO2, 95%CI -7 to 19 s, p = 0.37). Cerebral TOI and PaO2 were higher after O2/CO2 (+ 1.5%; 95%CI: from 0.3 to 2.6; p = 0.02 and + 0.6 kPa; 95%CI: 0.1 to 1.1; p = 0.02). CONCLUSION: O2/CO2 improves cerebral TOI and PaO2 in anesthetized bariatric patients. Better apnea tolerance could not be confirmed.

Heterogeneous evolution of SARS-CoV-2 seroprevalence in school-age children: Results from the school-based cohort study Ciao Corona in November-December 2021 in the canton of Zurich.

BACKGROUND: Much remains unknown regarding the evolution of SARS-CoV-2 seroprevalence and variability in seropositive children in districts, schools and classes as only a few school-based cohort studies exist. Vaccination of children, initiated at different times for different age groups, adds additional complexity to the understanding of how seroprevalence developed in the school aged population. AIM: We investigated the evolution of SARS-CoV-2 seroprevalence in children and its variability in districts, schools and classes in Switzerland from June/July 2020 to November/December 2021. METHODS: In this school-based cohort study, SARS-CoV-2 antibodies were measured in primary and secondary school children from randomly selected schools in the canton of Zurich in October/November 2020, March/April 2021 and November/December 2021. Seroprevalence was estimated using Bayesian logistic regression to adjust for test sensitivity and specificity. Variability of seroprevalence between school classes was expressed as maximum minus minimum seroprevalence in a class and summarised as median (interquartile range). RESULTS: 1875 children from 287 classes in 43 schools were tested, with median age 12 years (range 6-17), 51% 12+ vaccinated. Seroprevalence increased from 5.6% (95% credible interval [CrI] 3.5-7.6%) to 31.1% (95% CrI 27.0-36.1%) in unvaccinated children, and 46.4% (95% CrI 42.6-50.9%) in all children (including vaccinated). Earlier in the pandemic, seropositivity rates in primary schools were similar to or slightly higher (<5%) than those in secondary schools, but by late 2021, primary schools had 12.3% (44.3%) lower seroprevalence for unvaccinated (all) subjects. Variability in seroprevalence among districts and schools increased more than two-fold over time, and in classes from 11% (95% CrI 7-17%) to 40% (95% CrI 22-49%). CONCLUSIONS: Seroprevalence in children increased greatly, especially in 2021 following introduction of vaccines. Variability in seroprevalence was high and increased substantially over time, suggesting complex transmission chains.

Respiratory morbidity in preschool and school-age children born very preterm and its association with parents' health-related quality of life and family functioning.

The purpose of this study is to describe the prevalence and severity of respiratory symptoms in children born very preterm and to assess their association with parents' health-related quality of life (HRQoL) and family functioning. We conducted a cross-sectional study and recruited children born less than 32 weeks' gestation between January 2006 and December 2019, in the greater Zurich area, Switzerland. Between May and December 2021, parents were invited to complete an online survey for their preterm child and for a control term born (≥ 37 weeks' gestation) sibling aged 1 to 18 years. We used a validated questionnaire to assess respiratory symptoms and the Pediatrics Quality of Life Family Impact Module (PedsQL FIM) to assess parents' HRQoL and family functioning. The survey was completed for 616 very preterm children (99 with bronchopulmonary dysplasia (BPD)) and 180 controls. Girls made up 45% (46% in controls) of the sample, and 63% (60% in controls) of participants were aged 6 to 18 years (school-age). Very preterm children reported a higher risk of respiratory symptoms than controls, especially preschoolers and those with moderate-to-severe BPD. Parents of children with "mild" and "moderate-severe" respiratory symptoms had on average -3.9 (95%CI: -6.6 to -1.1) and -8.2 (-11.2 to -5.2) lower PedsQL FIM total score, respectively, than parents of children with no symptoms. The same pattern was observed after stratifying by age categories.  Conclusions: Our study suggests that respiratory morbidity in very preterm children has a negative impact on parents' HRQoL and family functioning, even beyond the first years of life. What is Known: • The burden of respiratory morbidity associated with very premature birth is high and last far beyond the neonatal period. • Respiratory morbidity contributes to lower health-related quality of life (HRQoL) in parents of very preterm children in early infancy. What is New: • Respiratory morbidity in very preterm children has a negative impact on parents' HRQoL and family functioning beyond the first years of life. • Parents of very preterm children with moderate and severe respiratory symptoms are the ones who report lower scores, both for preschool and school-age children.

Cystic fibrosis related diabetes is not associated with maximal aerobic exercise capacity in cystic fibrosis: a cross-sectional analysis of an international multicenter trial.

BACKGROUND: Previous studies have reported differences in aerobic exercise capacity, expressed as peak oxygen uptake (VO2peak), between people with and without cystic fibrosis (CF) related diabetes (CFRD). However, none of the studies controlled for the potential influence of physical activity on VO2peak. We investigated associations between CFRD and VO2peak following rigorous control for confounders including objectively measured physical activity. METHODS: Baseline data from the international multicenter trial ACTIVATE-CF with participants ≥12 years performing up to 4 h per week of vigorous physical activity were used for this project. Multivariable models were computed to study associations between CFRD and VO2peak (mL.min-1) adjusting for a set of pre-defined covariates: age, sex, weight, forced expiratory volume in 1 s (FEV1), breathing reserve index, Pseudomonas aeruginosa infection, and physical activity (aerobic step counts from pedometry). Variables were selected based on their potential confounding effect on the association between VO2peak and CFRD. RESULTS: Among 117 randomized individuals, 103 (52% female) had a maximal exercise test and were included in the analysis. Participants with (n = 19) and without (n = 84) CFRD did not differ in FEV1, physical activity, nutritional status, and other clinical characteristics. There were also no differences in VO2peak (mL.min-1 or mL.kg-1.min-1 or% predicted). In the final multivariable model, all pre-defined covariates were significant predictors of VO2peak (mL.min-1), however CFRD [coefficient 82.1, 95% CI -69.5 to 233.8, p = 0.28] was not. CONCLUSIONS: This study suggests no meaningful differences in VO2peak between people with and without CFRD given comparable levels of physical activity.

Survival modelling and cost-effectiveness analysis of treatments for newly diagnosed metastatic hormone-sensitive prostate cancer.

BACKGROUND: In metastatic hormone-sensitive prostate cancer (mHSPC) treatment, survival benefits have been shown by adding docetaxel or recent androgen receptor axis-targeted therapies (ARATs) abiraterone, apalutamide, or enzalutamide to androgen deprivation therapy (ADT). However, the optimal treatment strategy in terms of costs and effects is unclear, not least due to high ARAT costs. METHODS: To assess treatment cost-effectiveness, we developed a Markov cohort model with health states of progression-free disease, progressive disease and death for men with newly diagnosed mHSPC, with a 30-year time horizon. Survival data, adverse events and utilities were informed by randomized controlled trial results, our meta-analysis of re-created individual patient survival data, and publicly available sources of unit costs. We applied a Swiss healthcare payer perspective and discounted costs and effects by 3%. RESULTS: We found a significant overall survival benefit for ADT+abiraterone versus ADT+docetaxel. The corresponding incremental cost-effectiveness ratio (ICER) was predicted to be EUR 39,814 per quality-adjusted life-year (QALY) gained. ADT+apalutamide and ADT+enzalutamide incurred higher costs and lower QALYs compared to ADT+abiraterone. For all ARATs, drug costs constituted the most substantial cost component. Results were stable except for a large univariable reduction in the pre-progression utility under ADT+abiraterone and very large variations in drug prices. CONCLUSIONS: Our model projected ADT+abiraterone to be cost-effective compared to ADT+docetaxel at a willingness-to-pay threshold of EUR 70,400/QALY (CHF 100,000 applying purchasing power parities). Given lower estimated QALYs for ADT+apalutamide and ADT+enzalutamide compared to ADT+abiraterone, the former only became cost-effective (the preferred) treatment option(s) at substantial 75-80% (80-90%) price reductions.

Lifestyle Behaviours of Children and Adolescents During the First Two Waves of the COVID-19 Pandemic in Switzerland and Their Relation to Well-Being: An Observational Study.

Objectives: To describe changes in adherence to recommendations for physical activity (PA), screen time (ST), and sleep duration over the first two waves of the pandemic in Switzerland, and to assess the associations of these lifestyle behaviours with life satisfaction and overall health as well-being indicators. Methods: In this observational study, we included 2,534 participants (5-16 years) from four Swiss cantons. Participants, or their parents, completed repeated questionnaires and reported on their (child's) lifestyle and well-being, between June 2020 and April 2021. We used linear and logistic regression models to assess the associations between lifestyle and well-being. Results: The percentage of children meeting the recommendations for PA and ST decreased from the pre-pandemic period to the first wave, with a slight recovery during the second wave. Participants meeting all three recommendations during the second wave were more likely to report excellent health (OR: 1.65 [95% CI: 1.00-2.76]) and higher life satisfaction (ß: 0.46 [0.16-0.77]) in early 2021 than participants not meeting any recommendation. Conclusion: We showed a substantial impact of the COVID-19 pandemic on children's and adolescents' lifestyle, and a positive association between meeting lifestyle recommendations and well-being.

The impact of seat height on 1-min sit-to-stand test performance in COPD: a randomised crossover trial.

Study question: Is there a difference in the number of repetitions in the 1-minute sit-to-stand (1MSTS) test using an individually adapted seat height to 90° knee flexion (1MSTSIND), compared with the commonly used standard chair seat height of 46 cm (1MSTSSTD), in people with COPD? Methods: We conducted a single-centre, single-blinded, randomised crossover trial in people with COPD between August 2020 and March 2021 at a specialised rehabilitation clinic in Switzerland. After a learning 1MSTS test, all participants performed two 1MSTS tests in random order on consecutive days. Participants were blinded, as they did not receive detailed information on the testing protocols. Results: 49 individuals with COPD (47% female) participated. In a regression model adjusted for sequence period and subject, 1MSTS test performance was lower on 1MSTSIND compared to 1MSTSSTD (-0.78 repetitions, 95% CI -1.47 to -0.11). In a second regression model additionally including the knee angle and an interaction term (1MSTSIND×knee angle), the interaction term was significant: 0.18 (95% CI 0.05 to 0.30). The limits of agreement were between -5.5 and 4 repetitions. Conclusion: Although we observed a statistically significant difference between 1MSTSIND and 1MSTSSTD on a population level, the difference is negligible. Further studies may be needed to determine whether individual adaptation of seat height is needed for very tall or short people to ensure a valid assessment of 1MSTS test performance in COPD.