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Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm balance remain unclear.To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments.We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov until March 1, 2022. Randomized controlled trials (RCTs) comparing docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, and radiotherapy combined with androgen deprivation therapy (ADT) mutually or with ADT alone were eligible. Three reviewers independently performed screening, data extraction, and risk of bias assessment in duplicate.Across ten RCTs, we found relevant survival benefits for ADT + docetaxel (high certainty according to the Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), ADT + abiraterone (moderate certainty), ADT + enzalutamide (low certainty), ADT + apalutamide (high certainty), and ADT + docetaxel + darolutamide (high certainty) compared with ADT alone. ADT + radiotherapy appeared effective only in low-volume de novo mHSPC. We found a short-term HRQoL decrease lasting 3-6 mo for ADT + docetaxel (moderate certainty) and a potential HRQoL benefit for ADT + abiraterone up to 24 mo of follow-up (moderate certainty) compared with ADT alone. There was no difference in HRQoL for ADT + enzalutamide, ADT + apalutamide, or ADT + radiotherapy over ADT alone (low-high certainty). Grade 3-5 adverse effect rates were increased with all systemic combination treatments. A benefit-harm assessment showed high probabilities (60%) for a net clinical benefit with ADT + abiraterone, ADT + enzalutamide, and ADT + apalutamide, while ADT + docetaxel and ADT + docetaxel + darolutamide appeared unlikely (40%) to be beneficial.Despite substantial survival benefits, no systemic combination treatment showed a clear HRQoL improvement compared with ADT alone. We found evidence for a short-term HRQoL decline with ADT + docetaxel and a higher net clinical benefit with ADT + abiraterone, ADT + apalutamide and ADT + enzalutamide. While individualized decision-making remains important and economic factors need to be considered, the evidence may support a general preference for the combination of ADT with androgen receptor axis-targeted therapies over docetaxel-containing strategies.We assessed different combination treatments for metastatic hormone-sensitive prostate cancer. While survival was better with all systemic combination treatments, there was no clear improvement in health-related quality of life compared with androgen deprivation therapy alone. Novel hormonal combination treatments had a more favorable benefit-harm balance than combination treatments that include chemotherapy.

ObjectivesTo assess the longitudinal development of humoral immunity in children and adolescents during the COVID-19 pandemic, with a particular focus on how anti-spike IgG antibodies and neutralising response changed during the first Omicron peak (December 2021 to May 2022).DesignProspective school-based study during the COVID-19 pandemic (June 2020 to July 2022) including five testing rounds with corresponding cross-sectional cohorts and a longitudinal cohort who participated in at least four rounds.Setting55 randomly selected schools in the Canton of Zurich, Switzerland.ParticipantsBetween 1875 to 2500 children and adolescents per testing round and 751 in the longitudinal cohort.Main outcome measuresDevelopment of SARS-CoV-2 seroprevalence, anti-spike IgG antibodies and neutralising antibody response over time, persistence of antibodies and variation of antibody levels in individuals only infected, vaccinated or with hybrid immunity during the early Omicron period.ResultsBy July 2022 96.9% (95% credible interval [CrI] 95.2 to 98.1%) of children and adolescents had anti-spike IgG antibodies against SARS-CoV-2. The substantial increase in seroprevalence during the first peak of the Omicron wave was largely driven by primary infections in mostly unvaccinated children under the age of 12 (28.4% [95% CrI 24.2 to 33.2%] in December 2021, to 95.7% [95% CrI 93.4 to 97.4%] in July 2022). This stands in contrast to adolescents aged 12 years and older (69.4% [95% CrI 64.0 to 75.4%] in December 2021 to 98.4% [95% CrI 97.3 to 99.2%] in July 2022), who were eligible for vaccination since June 2021. Children and adolescents with hybrid immunity or immunity from vaccination had high anti-spike IgG titres (median Mean Fluorescence Intensity (MFI) ratio of 136.2 [Inter Quartile Range [IQR]: 121.9 to 154.3] and 127.6 [IQR: 114.1 to 151.0]) and strong neutralising responses (e.g., anti-Omicron 98.9% [95% Confidence Interval [CI] 96.0 to 99.7%] and 81.6% [95% CI 74.9 to 86.9%]). Meanwhile, infected but unvaccinated children and adolescents had substantially lower anti-spike IgG titres (median MFI ratio of 54.8 [IQR: 22.8 to 89.8]) and neutralising responses (e.g., anti-Omicron 64.9% [95% CI 59.8 to 69.7%]).ConclusionThese findings show that the Omicron wave and the rollout of vaccines led to almost 100% seropositivity and boosted anti-spike IgG titres and neutralising capacity in children and adolescents. This was particularly driven by unvaccinated children (

BackgroundEvidence from population-based studies on the impact of post COVID-19 condition (PCC) on ability to work is limited but critical due to its high prevalence among individuals of working-age.ObjectiveTo evaluate the association between PCC, work ability, and occupational changes.DesignPopulation-based, longitudinal cohort.SettingGeneral population, Canton of Zurich, Switzerland.Participants672 adults of working-age with SARS-CoV-2 infection.MeasurementsCurrent work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), as well as PCC-related occupational changes at one year after infection.ResultsThere was very strong evidence that current work ability scores were 0.62 (95% confidence interval (CI) 0.30 to 0.95) points lower among those with PCC compared to those without. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (odds ratio (OR) 0.30, 95% CI 0.20 to 0.46) and mental (OR 0.40, 0.27 to 0.62) demands among those with PCC compared to those without. Higher age and history of psychiatric diagnosis were associated with a more substantial reduction 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 and 43% of those with PCC-related occupational changes reporting financial difficulties as a result.LimitationsSelection, use of self-reported outcome measures, and limited generalizability to individuals with most severe COVID-19 or following vaccination.ConclusionsThese 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.Primary Funding SourceFederal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland.Study RegistrationISRCTN14990068.

ObjectivesBoth lifestyle and health-related quality of life (HRQOL) were compromised during the COVID-19 pandemic. We investigated changes in adherence to physical activity and screen time recommendations of children and adolescents throughout the pandemic, and their association with HRQOL.MethodsLongitudinal data in 1769 primary (grades 1-6) and secondary (7-9) school children ages 6-17 years was taken from Ciao Corona, a school-based prospective cohort study in Zurich, Switzerland, with 5 online questionnaires between June 2020 and July 2022. HRQOL was assessed using the KINDL questionnaire. Meeting physical activity and screen time recommendations was defined by the world health organization (WHO).ResultsAdherence to physical activity recommendations dropped in 2020, but returned to pre-pandemic levels by 2022. Fewer children met screen time recommendations in 2020 and 2021 than pre-pandemic. HRQOL reduced 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 recommendations.ConclusionsAdherence to WHO guidelines on physical activity and screen time during the pandemic had a consistent association with HRQOL despite longitudinal changes in behavior.

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.

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.

Objective The aim of this study was to pool data from randomized controlled trials (RCT) limited to resectable pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy impacts on disease-free survival (DFS) and surgical outcome. Summary background data Few underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations. Methods Three RCTs were identified comparing neoadjuvant chemo (± radio) therapy vs. upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards. Results A total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4-0.9] (P = 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35-0.9, P = 0.045). Although postoperative complications (Comprehensive Complication Index, CCI®) occurred less frequently (P = 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters. Conclusion Neoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.

BACKGROUND: Few studies have directly examined the incidence or seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children, parents and teachers from the same school communities. This study aimed to describe SARS-CoV-2 seroprevalence within cantonal districts and school communities in children, parents and school personnel in June-September 2020 and March-April 2021 in the canton of Zürich, Switzerland. METHODS: We invited children from 55 randomly selected primary and secondary schools and 275 classes within them to participate in the Ciao Corona study in June-July 2020. Parents of the participating children and all school personnel were invited in August-September 2020. Eligible classes, parents and school personnel were tested again in March-April 2021. Venous blood was tested for SARS-CoV-2 serology. We collected sociodemographic information of the participants in online questionnaires on enrolment in the study. We excluded vaccinated adults and those with unverified vaccination status from the main analysis. Seroprevalence estimates were adjusted for test accuracy. We assessed the variability of seroprevalence within and across cantonal districts and school communities and compared it with the per capita cumulative incidence of confirmed SARS-CoV-2 infections. RESULTS: In June-September 2020, 2,473 children, 1,608 school personnel and 2,045 parents participated in the study. In June-September 2020, seroprevalence was low (4.4% to 5.8%) in all cohorts. In March-April 2021, seroprevalence in children and parents (18.1% and 20.9%) was slightly higher than in school personnel (16.9%). We observed a large variation in seroprevalence estimates of the three cohorts within and between districts and school communities, with the median ratio of children’s seroprevalence to per capita confirmed cases in district inhabitants of 3.1 (interquartile range 2.6 to 3.9). Seroprevalence was lower in children in the upper school level and their parents, but not teachers. Children’s seroprevalence was slightly higher in classes with infected main teachers and families with one infected parent and substantially higher in families with two infected parents. CONCLUSIONS: We observed similar seroprevalence in children and parents, somewhat lower in school personnel in March-April 2021 and striking variation between districts and school communities. Children’s seroprevalence was higher in classes with infected main teachers and from families with infected parents.

ObjectiveTo estimate effectiveness of tickborne encephalitis (TBE) vaccination by time interval (DesignA retrospective, matched case–control studyParticipantsCases—all adult (age 18–79) TBE cases in Switzerland reported via the national mandatory disease reporting surveillance system from 2006 to 2020 (final n=1868). Controls—community controls from a database of randomly selected adults (age 18–79) participating in a 2018 cross-sectional study of TBE vaccination in Switzerland (final n=4625).Primary outcome measuresFor cases and controls, the number of TBE vaccine doses received and the time since last vaccination were determined. Individuals were classified as being ‘unvaccinated’ (0 doses), ‘incomplete’ (1–2 doses) or ‘complete’ (3+ doses). Individuals with ‘complete’ vaccination were further classified by time since the last dose was received (ResultsVE for incomplete vaccination was 76.8% (95% CI 69.0% to 82.6%). For complete vaccination, overall VE was 95.0% (95% CI 93.5% to 96.1%). When the most recent dose was received ConclusionsThat VE does not decrease among completely vaccinated individuals over 10+ years since last vaccination supports the longevity of the protective response following complete TBE vaccination. Our findings support the effectiveness of 10-year TBE booster intervals currently used in Switzerland.

IntroductionSeroprevalence and transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents, especially in school setting, are not clear. Resulting uncertainty is reflected in very different decisions on school closures and reopenings across countries. The aim of this longitudinal cohort study is to assess the extent and patterns of seroprevalence of SARS-CoV-2 antibodies in school-attending children repeatedly. It will examine risk factors for infection, relationship between seropositivity and symptoms, and temporal persistence of antibodies. Additionally, it will include testing of school personnel and parents.Methods and analysisThe study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children aged 5 to 16 years, attending classes in primary and secondary schools are invited. Venous blood and saliva samples are collected for SARS-CoV-2 serological testing after the first wave of infections (June/July 2020), in fall (October/November 2020), and after winter (March/April 2021). Venous blood is also collected for serological testing of parents and school personnel. Bi-monthly questionnaires to children, parents and school personnel cover SARS-CoV-2 symptoms and tests, health, preventive behavior, lifestyle and quality of life information. Total seroprevalence and cumulative incidence will be calculated. Hierarchical Bayesian logistic regression models will account for sensitivity and specificity of the serological test in the analyses and for the complex sampling structure, i.e., clustering within classes and schools.Ethics and disseminationThe study was approved by the Ethics Committee of the Canton of Zurich, Switzerland (2020-01336). The results of this study will be published in peer-reviewed journals and will be made available to study participants and participating schools, the Federal Office of Public Health, and the Educational Department of the canton of Zurich. Trial registration numberNCT04448717.Ciao Corona is a large, prospective school-based cohort study and will provide robust data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence, transmission routes and immunity over time in a representative sample of school children.The longitudinal design will allow describing temporal trends of immunity to SARS-CoV-2 infection and to evaluate effects of school structure and preventive measures.This study will inform goal-oriented policy decisions in school management during subsequent outbreaks.Participation bias, missing questionnaires, desirability bias, and loss of follow up may occur. The validity of serological tests may also hamper results.

SUMMARYBackgroundPrevious studies assessing the impact of the COVID-19 pandemic on children’s and adolescent’s lifestyle focused mainly on the first wave in early 2020. We aimed 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 (March-May 2020 and October 2020-January 2021) in Switzerland, and to assess the associations of these lifestyle behaviours with life satisfaction and overall health, as indicators of well-being.MethodsWe included 3168 participants aged 5 to 18 years from four Swiss cantons. Participants or their parents completed repeated questionnaires and reported on their (child’s) PA, ST, sleep, life satisfaction, and overall health. We analysed lifestyle behaviours in terms of adherence to international recommendations. We used linear and logistic regression models to assess the associations of number of recommendations met and adherence patterns with well-being indicators.FindingsCompared to the pre-pandemic period, the percentage of participants meeting the recommendations for PA and ST decreased strikingly during March-May 2020, while there was a slight increase in those meeting recommendations for sleep. During October 2020-January 2021, the percentage of compliant children for PA and ST increased but remained lower than before the pandemic. Participants meeting all three recommendations were more likely to report excellent health (OR: 1·87 [1·15-3·08]) and a higher life satisfaction score (β: 0·59 [0·30-0·88]) than participants not meeting any recommendation. Adherence to recommendations for PA and sleep, PA and ST, and sleep and ST was similarly associated with both well-being indicators.InterpretationWe show a substantial impact of the COVID-19 pandemic on children’s and adolescents’ lifestyle behaviours with a partial recovery over time, and an association between lifestyle and well-being. Public health policies to promote children’s and adolescents’ well-being should target PA, ST, and sleep simultaneously.FundingCorona Immunitas.RESEARCH IN CONTEXTEvidence before the studyWe searched PubMed for studies assessing the effects of the COVID-19 pandemic on children’s and adolescents’ lifestyle behaviours, published up to September 6, 2021, with no language restrictions. Of the studies found, nearly all compared lifestyle behaviours before and during the strict confinement in the first wave of the pandemic, and very few studies extended their assessment beyond June 2020. The only longitudinal study assessing lifestyle changes up to 2021 included a sample of nineteen boys. Some studies assessed the association between lifestyle behaviours and well-being after the outbreak of the pandemic, but all used a single-behaviour approach (i.e., evaluated only one lifestyle behaviour) and no study considered the combined contribution of physical activity (PA), screen time (ST), and sleep. In addition, most studies were cross-sectional and did not consider pre-pandemic lifestyle behaviours.Added value of this studyThis is the first study assessing changes in adherence to international recommendations regarding PA, ST, and sleep duration in children and adolescents during the first two waves of the COVID-19 pandemic and the joint associations of these lifestyle behaviours with well-being. We used data from 3168 children and adolescents from four different Swiss cantons. We included measurements of PA, ST, and sleep before the pandemic, during the first wave between March and May 2020, and during the second wave between October 2020 and January 2021. We also assessed life satisfaction and overall health as indicators of well-being, between January and April 2021. We showed that, compared to the pre-pandemic period, the proportion of children and adolescents following the recommendations for PA and ST decreased during the first wave (lockdown period), while there was a slight increase in those meeting recommendations for sleep. During the second wave, the prevalence of compliant children and adolescents for PA and ST recovered but remained below pre-pandemic levels. Furthermore, we found an association between the number of recommendations met for lifestyle behaviours during the second wave and well-being assessed between January and April 2021. In contrast, there was no such association for the periods before the pandemic or during the lockdown. Participants following the recommendations for all three lifestyle behaviours or for combinations of two of them in the second wave were more likely to report excellent health and had a higher life satisfaction score, than those not meeting any recommendation.Implications of all the available evidenceOur findings demonstrate that the COVID-19 pandemic has had a strong negative effect on children’s and adolescents’ lifestyle behaviours, but some recovery has taken place within the first year since the outbreak. Policymakers should imperatively consider the balance of disease prevention and promotion of a healthy lifestyle when (re-)activating restrictive measures. Given the already high prevalence of children and adolescents not meeting lifestyle recommendations in the pre-pandemic period, our findings highlight the urgent need for public health policies aiming to avoid permanent negative changes on children’s and adolescents’ lifestyle and to mitigate the health risks associated with adverse changes during the pandemic. In addition, our study indicates that lifestyle is an important predictor of children’s and adolescents’ well-being, and it further suggests that future public health strategies aiming to promote well-being should target sufficient time for PA and sleep as well as reduce ST.

BACKGROUND: Few studies have explored the spread of SARS-CoV-2 in schools in 2021, with the advent of variants of concern. We aimed to examine the evolution of the proportion of seropositive children at schools from June-July 2020 to March-April 2021. We also examined symptoms, under-detection of infections, potential preventive effect of face masks, and reasons for non-participation in the study. METHODS: Children in lower (7–10 years), middle (8–13 years) and upper (12–17 years) school levels in randomly selected schools and classes in the canton of Zurich, Switzerland, were invited to participate in the prospective cohort study Ciao Corona. Three testing rounds were completed in June-July 2020, October-November 2020 and March-April 2021. From 5230 invited, 2974 children from 275 classes in in 55 schools participated in at least one testing round. We measured SARS-CoV-2 serology in venous blood, and parents filled in questionnaires on sociodemographic information and symptoms. RESULTS: The proportion of children seropositive for SARS-CoV-2 increased from 1.5% (95% credible interval [CrI] 0.6–2.6%) by June-July 2020, to 6.6% (4.0–8.9%) by October-November, and to 16.4% (12.1–19.5%) by March-April 2021. By March-April 2021, children in upper school level (12.4%; 7.3–16.7%) were less likely to be seropositive than those in middle (19.5%; 14.2–24.4%) or lower school levels (16.0%; 11.0–20.4%). The ratio of PCR-diagnosed to all seropositive children changed from one to 21.7 (by June-July 2020) to one to 3.5 (by March-April 2021). Potential clusters of three or more newly seropositive children were detected in 24 of 119 (20%) classes, 17 from which could be expected by chance. Clustering was not higher than expected by chance in middle and upper school levels. Children in the upper school level, who were wearing face masks at school from November 2020, had a 5.1% (95% confidence interval 9.4% to 0.7%) lower than expected seroprevalence by March-April 2021 than those in middle school level, based on difference-in-differences analysis. Symptoms were reported by 37% of newly seropositive and 16% seronegative children. Fear of blood sampling (64%) was the most frequently reported reason for non-participation. CONCLUSIONS: Although the proportion of seropositive children increased from 1.5% in June-July 2020 to 16.4% in March-April 2021, few infections were likely associated with potential spread within schools. In March-April 2021, significant clustering of seropositive children within classes was observed only in the lower school level. Trial Registration: ClinicalTrials.gov NCT04448717

BackgroundMask wearing contributes to the reduction of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Switzerland, compulsory use of masks was introduced in indoor public spaces and later in schools. In the canton of Zurich, masks were introduced for secondary school children (grades 7-9) from November 2020, and for primary school children (grades 4-6) from February 2021– along with other protective measures against SARS-CoV-2. This study explored perceptions towards the usefulness of masks in school and public in a cohort of children and adolescents in the canton of Zurich, Switzerland, in January – May 2021.MethodsSchool children aged 10 to 17 years enrolled in Ciao Corona, a prospective school-based cohort study, responded to nested online surveys between January 12 to March 24 2021 (Q1) and March 10 to May 16 2021 (Q2). Secondary school children were surveyed at Q1 and Q2, and primary school children at Q2 only. Surveys for parents and their children included questions on children’s perception of the usefulness of masks and mask wearing behavior. Associations between perceived usefulness of masks and child’s school level, gender, and parents’ educational attainment were analyzed with Pearson’s and McNemar’s chi-squared tests. Free-text comments provided by children were classified into categories of expressed attitude towards mask wearing.Results595 (54% girls) and 1118 (52% girls) school children responded to online questionnaires at Q1 and Q2, respectively. More than half of school children perceived masks to be useful at school (Q1:60% and Q2:57%) and in public (Q1:69% and Q2:60%). Girls perceived masks as useful more often than boys (at Q2 at school: 61% versus 53%, in public: 64% versus 57%), and children of parents with high educational attainment more often than those of parents with lower educational attainment (at Q2 at school: 61% versus 49%, in public: 63% versus 54%). There were no differences in the perceived usefulness of masks among children in primary versus secondary school. At Q1 and Q2 each, about 20% of children provided individual statements about masks, of which 36% at Q1 and 16% at Q2 reported side-effects and discomfort such as skin irritations, headache or difficulties breathing during physical education.ConclusionApproximately 60% of school children perceived masks at school and in public places as useful. A small but non-negligible proportion of children reported discomfort and side-effects that should be considered to ensure high adherence to mask wearing among school children.Trial registrationClinicalTrials.govNCT04448717https://clinicaltrials.gov/ct2/show/NCT04448717CONTRIBUTION TO THE FIELD STATEMENTWorldwide about 150 countries fully closed their schools at some point during the coronavirus pandemic, while other countries – such as Switzerland – kept schools open almost all the time. However, among other protective measures, children in secondary school (aged approximately 14-16 years) had to wear masks since November 2020, and older children in primary school (aged 11-13 years) – since February 2021.As part of the large study Ciao Corona based in schools in Switzerland, we wanted to learn how children perceive the usefulness of masks in school and public. Children and their parents completed questionnaires in January-March (595 secondary school children) and March-May 2021 (1118 secondary and primary school children).We found that about 60% of children perceived masks to be useful at school and in public. Girls perceived masks as useful more often than boys, and children of parents with university or college education more often than those of parents with lower education. About 7– 9% of children reported side-effects and discomfort such as skin irritations, headache or difficulties breathing during physical education. Although side-effects were not frequently reported, they should be considered to ensure high adherence to mask wearing among school children.

Objective: To assess the predictive value of symptoms, sociodemographic characteristics, and SARS-CoV-2 exposure in household, school, and community setting for SARS-CoV-2 seropositivity in Swiss schoolchildren at two time points in 2020.Design: Serological testing of children in primary and secondary schools (aged 6–13 and 12–16 years, respectively) took place in June–July (T1) and October–November (T2) 2020, as part of the longitudinal, school-based study Ciao Corona in the canton of Zurich, Switzerland. Information on sociodemographic characteristics and clinical history was collected with questionnaires to parents; information on school-level SARS-CoV-2 infections was collected with questionnaires to school principals. Community-level cumulative incidence was obtained from official statistics. We used logistic regression to identify individual predictors of seropositivity and assessed the predictive performance of symptom- and exposure-based prediction models.Results: A total of 2,496 children (74 seropositive) at T1 and 2,152 children (109 seropositive) at T2 were included. Except for anosmia (odds ratio 15.4, 95% confidence interval [3.4–70.7]) and headache (2.0 [1.03–3.9]) at T2, none of the individual symptoms were significantly predictive of seropositivity at either time point. Of all the exposure variables, a reported SARS-CoV-2 case in the household was the strongest predictor for seropositivity at T1 (12.4 [5.8–26.7]) and T2 (10.8 [4.5–25.8]). At both time points, area under the receiver operating characteristic curve was greater for exposure-based (T1, 0.69; T2, 0.64) than symptom-based prediction models (T1, 0.59; T2, 0.57).Conclusions: In children, retrospective identification of past SARS-CoV-2 infections based on symptoms is imprecise. SARS-CoV-2 seropositivity is better predicted by factors of SARS-CoV-2 exposure, especially reported SARS-CoV-2 cases in the household. Predicting SARS-CoV-2 seropositivity in children in general is challenging, as few reliable predictors could be identified. For an accurate retrospective identification of SARS-CoV-2 infections in children, serological tests are likely indispensable.Trial registration number: NCT04448717.

ObjectivesTo determine the variation in SARS-CoV-2 seroprevalence in school children and the relationship with self-reported symptoms.DesignBaseline measurements of a longitudinal cohort study (Ciao Corona) from June to July 2020.Setting55 schools stratified by district in the canton of Zurich, Switzerland.Participants2585 children (1339 girls; median age: 11 years, age range: 6–16 years), attending grades 1–2, 4–5 and 7–8.Main outcome measuresVariation in seroprevalence of SARS-CoV-2 in children across 12 cantonal districts, schools and grades, assessed using Luminex-based test of four epitopes for IgG, IgA and IgM (Antibody Coronavirus Assay,ABCORA 2.0). Clustering of cases within classes. Association of seropositivity and symptoms. Comparison with seroprevalence in adult population, assessed using Luminex-based test of IgG and IgA (Sensitive Anti-SARS-CoV-2 Spike Trimer Immunoglobulin Serological test).ResultsOverall seroprevalence was 2.8% (95% CI 1.5% to 4.1%), ranging from 1.0% to 4.5% across districts. Seroprevalence in grades 1–2 was 3.8% (95% CI 2.0% to 6.1%), in grades 4–5 was 2.4% (95% CI 1.1% to 4.2%) and in grades 7–8 was 1.5% (95% CI 0.5% to 3.0%). At least one seropositive child was present in 36 of 55 (65%) schools and in 44 (34%) of 131 classes where ≥5 children and ≥50% of children within the class were tested. 73% of children reported COVID-19-compatible symptoms since January 2020, with the same frequency in seropositive and seronegative children for all symptoms. Seroprevalence of children and adults was similar (3.2%, 95% credible interval (CrI) 1.7% to 5.0% vs 3.6%, 95% CrI 1.7% to 5.4%). The ratio of confirmed SARS-CoV-2 cumulative incidence-to-seropositive cases was 1:89 in children and 1:12 in adults.ConclusionsSARS-CoV-2 seroprevalence was low in children and similar to that in adults by the end of June 2020. Very low ratio of diagnosed-to-seropositive children was observed. We did not detect clustering of SARS-CoV-2-seropositive children within classes, but the follow-up of this study will shed more light on transmission within schools.Trial registration numberNCT04448717.

In Europe, two commercial devices are available to measure combined single-breath diffusing capacity of the lung for nitric oxide (DLNO) and carbon monoxide (DLCO) in one manoeuvre. Reference values were derived by pooling datasets from both devices, but agreement between devices has not been established. We conducted a randomised crossover trial in 35 healthy adults (age 40.0±15.5 years, 51% female) to compare DLNO (primary end-point) between MasterScreen™ (Vyaire Medical, Mettawa, IL, USA) and HypAir (Medisoft, Dinant, Belgium) devices during a single visit under controlled conditions. Linear mixed models were used adjusting for device and period as fixed effects and random intercept for each participant. Difference in DLNO between HypAir and MasterScreen was 24.0 mL·min−1·mmHg−1 (95% CI 21.7–26.3). There was no difference in DLCO (−0.03 mL·min−1·mmHg−1, 95% CI −0.57–0.12) between devices while alveolar volume (VA) was higher on HypAir compared to MasterScreen™ (0.48 L, 95% CI 0.45–0.52). Disparity in the estimation of VA and the rate of NO uptake (KNO=DLNO/VA) could explain the discrepancy in DLNO between devices. Disparity in the estimation of VA and the rate of CO uptake (KCO=DLCO/VA) per unit of VA offset each other resulting in negligible discrepancy in DLCO between devices. Differences in methods of expiratory gas sampling and sensor specifications between devices likely explain these observations. These findings have important implications for derivation of DLNO reference values and comparison of results across studies. Until this issue is resolved, reference values, established on the respective devices, should be used for test interpretation., Large discrepancies between commercial devices to measure single-breath diffusing capacity of the lung for nitric oxide in healthy subjects caution against pooling or direct comparison of measurements obtained using different protocols and devices https://bit.ly/3vKyF7U

Study Objectives: Patients who have experienced heart failure with central sleep apnea/Cheyne-Stokes respiration (CSA/CSR) have an impaired prognosis. Continuous positive airway pressure (CPAP) and adaptive servoventilation (ASV) as well as nocturnal oxygen (O2) are proposed treatmentmodalities of CSA/CSR. The goal of the study is to assess whether and how different treatments of CSA/CSR affect cardiac function. Methods: Databases were searched up to December 2017 for randomized controlled trials (RCTs) comparing the effect of any combination of CPAP, ASV, O2 or an inactive control on left ventricular ejection fraction (LVEF) in patients with heart failure and CSA/CSR. A systematic review and network meta-analysis using multivariate random-effects meta-regression were performed. Results: Twenty-four RCTs (1,289 patients) were included in the systematic review and data of 16 RCTs (951 patients; apnea-hypopnea-index 38 ± 3/h, LVEF 29 ± 3%) could be pooled in a network meta-analysis. Compared to an inactive control, both CPAP and ASV significantly improved LVEF by 4.4% (95% confidence interval 0.3-8.5%, P = 0.036) and 3.8% (95% confidence interval 0.6-7.0%, P = 0.025), respectively, whereas O2 had no effect on LVEF (P = 0.35). There was no difference in treatment effects on LVEF between CPAP and ASV (P = 0.76). The treatment effect of positive pressure ventilation was larger when baseline LVEF was lower in systolic heart failure. Conclusions: CPAP and ASVare effective in improving LVEF in patients with heart failure and CSA/CSR to a clinically relevant amount, whereas nocturnal O2 is not. There is no difference between CPAP and ASV in the comparative beneficial effect on cardiac function.

The aim of this investigation was to elucidate the effect of CPAP withdrawal on neurometabolic and cardiometabolic markers in patients with obstructive sleep apnoea. We evaluated 70 patients (mean age 61±10 years, 82% men) treated with CPAP in two 2-week, parallel, randomised controlled trials. CPAP withdrawal resulted in elevated 3,4-dihydroxyphenylglycol, norepinephrine and cortisol after 2 weeks of CPAP withdrawal; however, no statistically significant changes of the renin–angiotensin–aldosterone system (RAAS) determinants were documented. In summary, CPAP withdrawal may be more prominently linked to short-term increases in sympathetic activation than hypothalamic–pituitary–adrenal axis or RAAS activation. ClinicalTrials.gov Identifier: NCT02493673 and NCT02050425.

Objectives To examine longitudinal changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and to determine the clustering of children who were seropositive within school classes in the canton of Zurich, Switzerland from June to November 2020. Design Prospective cohort study. Setting Switzerland had one of the highest second waves of the SARS-CoV-2 pandemic in Europe in autumn 2020. Keeping schools open provided a moderate to high exposure environment to study SARS-CoV-2 infections. Children from randomly selected schools and classes, stratified by district, were invited for serological testing of SARS-CoV-2. Parents completed questionnaires on sociodemographic and health related questions. Participants 275 classes in 55 schools; 2603 children participated in June-July 2020 and 2552 in October-November 2020 (age range 6-16 years). Main outcome measures Serology of SARS-CoV-2 in June-July and October-November 2020, clustering of children who were seropositive within classes, and symptoms in children. Results In June-July, 74 of 2496 children with serological results were seropositive; in October-November, the number had increased to 173 of 2503. Overall SARS-CoV-2 seroprevalence was 2.4% (95% credible interval 1.4% to 3.6%) in the summer and 4.5% (3.2% to 6.0%) in late autumn in children who were not previously seropositive, leading to an estimated 7.8% (6.2% to 9.5%) of children who were ever seropositive. Seroprevalence varied across districts (in the autumn, 1.7-15.0%). No significant differences were found among lower, middle, and upper school levels (children aged 6-9 years, 9-13 years, and 12-16 years, respectively). Among the 2223 children who had serology tests at both testing rounds, 28/70 (40%) who were previously seropositive became seronegative, and 109/2153 (5%) who were previously seronegative became seropositive. Symptoms were reported for 22% of children who were seronegative and 29% of children who were newly seropositive since the summer. Between July and November 2020, the ratio of children diagnosed with SARS-CoV-2 infection to those who were seropositive was 1 to 8. At least one child who was newly seropositive was detected in 47 of 55 schools and in 90 of 275 classes. Among 130 classes with a high participation rate, no children who were seropositive were found in 73 (56%) classes, one or two children were seropositive in 50 (38%) classes, and at least three children were seropositive in 7 (5%) classes. Class level explained 24% and school level 8% of variance in seropositivity in the multilevel logistic regression models. Conclusions With schools open since August 2020 and some preventive measures in place, clustering of children who were seropositive occurred in only a few classes despite an increase in overall seroprevalence during a period of moderate to high transmission of SARS-CoV-2 in the community. Uncertainty remains as to whether these findings will change with the new variants of SARS-CoV-2 and dynamic levels of community transmission. Trial registration NCT04448717

The aim of this study was to determine if there is a difference in 6-min walk test (6MWT) distance when the assessor accompanies the patient to continuously measure peripheral oxygen saturation (SpO2) compared to the patient walking unaccompanied. We conducted a randomised crossover study to evaluate the impact of the assessor walking with the patient during the 6MWT (6MWTwith) versus the patient walking alone (6MWTwithout). At the end of a pulmonary rehabilitation programme, each patient performed two 6MWTs in random order and separated by a 30-min rest. 49 patients with chronic obstructive pulmonary disease (COPD) (Global Initiative for Obstructive Lung Disease classification II–IV) were included. In a regression model adjusting for period and subject, accompanying the patient resulted in a lower walking distance (mean difference −9.1 m, 95% CI −13.9– −4.3, p=0.0004). Notably, six patients walked more than 30 m farther (minimal important difference) in one of the two conditions (6MWTwith: n=1, 6MWTwithout: n=5). There were no between-sequence-group differences in heart rate, dyspnoea, leg fatigue and SpO2. The median (interquartile range) number and duration of SpO2 signal artefacts were high but not different between the experimental conditions (6MWTwith: 17 (4–24), 34 s (7–113 s); 6 MWTwithout: 11 (3–26), 24 s (4–62 s)). At a study population level, we observed a statistically significant difference in 6MWT distance between the two experimental conditions; however, the magnitude of difference was small and may not be clinically relevant. Nevertheless, in a clinical setting, unaccompanied walking resulted in a substantially higher walking distance in individual patients, pointing towards strictly standardised testing methodology, in particular in pre–post study designs., Accompanied walking during a 6MWT versus unaccompanied walking results in shorter walked distance (mean difference −9.1 m, 95% CI −13.9– −4.3 m). No differences in nadir SpO2 or oximetry artefacts were noted between accompanied and unaccompanied walking. https://bit.ly/3tBjfCq

ObjectivesTo longitudinally assess severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and clustering of seropositive children within school classes in March-April 2021 compared to June-July and October-November 2020. To examine the evolution of symptoms and the extent of under-detection of SARS-CoV-2 in children.DesignProspective cohort study of randomly selected schools and classes.SettingSchools remained open for physical attendance in Switzerland from May 2020 to the end of 2020/2021 school year. Lower school level (age range 7-10 years) and middle school level (8-13 years) children in primary schools, and upper school level (12-17 years) children in secondary schools were invited for SARS-CoV-2 serological testing in the Ciao Corona study in the canton of Zurich, Switzerland. Three testing rounds were completed in June-July 2020 (T1; after the first wave of SARS-CoV-2 infections), October-November 2020 (T2; during the peak of the second wave), and March-April 2021 (T3; after the second wave and with SARS-CoV-2 variants of concern becoming dominant). Parents completed questionnaires on sociodemographic information and symptoms.Participants2487 children (median age 12 years, age range 7-17 years) recruited from 275 classes in 55 schools participated in the testing in March-April 2021; total of 2974 children participated in at least one of the 3 testing rounds.Main outcome measuresSARS-CoV-2 serology results; clustering of seropositive children within classes; reported symptoms.ResultsThe proportion of children who were SARS-CoV-2 seropositive increased from 1.5% (95% credible interval (CrI) 0.6% to 2.6%) in June-July 2020, to 6.6% (95% CrI 4.0% to 8.9%) in October-November, and to 16.4% (95% CrI 12.1% to 19.5%) in March-April 2021. By March-April 2021, children in upper school level (12.4%; 95% CrI 7.3% to 16.7%) were less likely to be seropositive than those in middle (19.5%; 95% CrI 14.2% to 24.4%) or lower school levels (16.0%; 95% CrI 11.0% to 20.4%). Children in the upper school level had a 5.1% (95% CI -9.4% to -0.7%) lower than expected seroprevalence by March-April 2021 than those in middle school level, based on difference-in-differences analysis. The ratio of PCR-diagnosed to all seropositive children changed from 1 to 21.7 (by June-July 2020) to 1 to 3.5 (by March-April 2021). Symptoms were reported by 37% of newly seropositive and 16% seronegative children. Potential clusters of 3 or more newly seropositive children were detected in 24 of 119 (20%) classes with a high participation rate, from which a median of 17 clusters could be expected due to random distribution of seropositive children within the classes. Clustering was lowest in middle and upper school levels. Retention rate in the cohort was high (84% of T1 participants attended T3). Among participants, supporting society and research were reported more commonly for participation than personal reasons. Fear of blood sampling was the most frequently reported reason for non-participation, reported for 64% of children.ConclusionsBy March-April 2021, 16.4% of children and adolescents were seropositive in the canton of Zurich, Switzerland. The majority of clusters of SARS-CoV-2 seropositive children in school classes could be explained by community rather than intra-class transmission of infections. Seroprevalence and clustering was lowest in upper school levels during all timepoints.Trial registrationClinicalTrials.govNCT04448717.What is already known on the topicTransmission of SARS-CoV-2 in school setting largely followed community transmission in 2020.With implemented preventive measures, secondary attack rates were low and clustering of SARS-CoV-2 infections within classes and schools (outbreaks) were observed rarely.What this study addsWith high community incidence and new variants of SARS-CoV-2, seroprevalence increased in school children between October 2020 – March 2021 in the canton of Zurich in Switzerland, and was higher in lower school levels.Most of the potential clusters of children who tested seropositive within classes could be explained by community rather than intra-class transmission of SARS-CoV-2, especially in middle and upper school levels.More children who tested seropositive in March-April 2021 were diagnosed and reported symptoms potentially related to SARS-CoV-2 infection more frequently than those who tested seropositive in June-July or October-November 2020.The most frequent reason for non-participation was fear of blood sampling (62% of children).

Background We have recently reported reduced physical activity (PA) in people with cystic fibrosis (pwCF) with and without lung transplantation (LTX) during a 6-week stringent lockdown in Switzerland. This follow-up study explores the impact of coronavirus-2019 disease (COVID-19) related pandemic restrictions on individuals’ therapy regimens and health-related aspects in pwCF. Methods We conducted a cross-sectional web-based national survey in Spring 2021. The survey included questions on daily PA, airway clearance and inhalation therapy, questions on COVID-19-compatible symptoms, diagnostic tests and vaccination status, and enquired health-related aspects covering the pandemic period between March 2020 to April 2021. Results 193 individuals with CF (53% female; 25% LTX recipients) participated. Among pwCF, 10 reported COVID-19 (n = 2 LTX recipients), two subjects were hospitalized, no invasive ventilation required, no deaths. The clinical course was generally mild. Overall, 46% reported less PA during the pandemic, mostly due to closed fitness facilities (85%), lack of motivation (34%), and changes in daily structures (21%). In contrast, 32/193 (17%) pwCF were able to increase their PA levels: 12 (38%) and 11 (34%) reported undertaking home-based training and outdoor activities more frequently; 6 (19%) reported an increase in routine PA, and another 3 (9%) started new activities. Among pwCF without LTX, 5% and 4% reported to undertake less airway clearance and inhalation therapy, respectively. Conclusions Our study reveals unfavorable consequences of COVID-19 pandemic restrictions on PA of pwCF with unknown long-term consequences for their overall physical fitness and lung health. Strategies to overcome this undesirable situation are needed; increased uptake of telehealth PA programs and virtual exercise classes to promote PA participation might be one promising approach along with vaccination of pwCF and their close contacts.

Background: The impact of nitrogen dioxide (NO2) and particulate matter with an aerodynamic diameter of less than or equal to 2.5. microns (PM2.5) exposures on lung function has been investigated mainly in children and less in adults. Furthermore, it is unclear whether short-term deviations of air pollutant concentration need to be considered in long-term exposure models. Objectives: The aims of this study were to investigate the association between short-term air pollution exposure and lung function and to assess whether short-term deviations of air pollutant concentration should be integrated into long-term exposure models. Methods: Short-term (daily averages 0–7 d prior) and long-term (1- and 4-y means) NO2 and PM2.5 concentrations were modeled using satellite, land use, and meteorological data calibrated on ground measurements. Forced expiratory volume within the first second (FEV1) of forced exhalation and forced vital capacity (FVC) were measured during a LuftiBus assessment (2003–2012) and linked to exposure information from the Swiss National Cohort for 36,085 adults (ages 18–95 y). We used multiple linear regression to estimate adjusted associations, and additionally adjusted models of long-term exposures for short-term deviations in air pollutant concentrations. Results: A 10μg/m3 increase in NO2 and PM2.5 on the day of the pulmonary function test was associated with lower FEV1 and FVC (NO2: FEV1 −8.0 ml [95% confidence interval: −13.4, −2.7], FVC −16.7 ml [−23.4, −10.0]; PM2.5: FEV1 −15.3 ml [−21.9, −8.7], FVC −18.5 ml [−26.5, −10.5]). A 10μg/m3 increase in 1-y mean NO2 was also associated with lower FEV1 (−7.7 ml; −15.9, 0.5) and FVC (−21.6 ml; −31.9, −11.4), as was a 10μg/m3 increase in 1-y mean PM2.5 (FEV1: −42.2 ml; −56.9, −27.5; FVC: −82.0 ml; −100.1, −63.9). These associations were robust to adjustment for short-term deviations in the concentration of each air pollutant. Conclusions: Short- and long-term air pollution exposures were negatively associated with lung function, in particular long-term PM2.5 exposure with FVC. Our findings contribute substantially to the evidence of adverse associations between air pollution and lung function in adults. https://doi.org/10.1289/EHP7529

Background and aimsThe facilitating role of schools in SARS-CoV-2 infection spread is still debated and the potential of school closures to mitigate transmission unclear. In autumn 2020, Switzerland experienced one of the highest second waves of the SARS-CoV-2 pandemic in Europe while keeping schools open, thus offering a high-exposure environment to study SARS-CoV-2 infections in schools. The aim of this study was to examine longitudinal change in SARS-CoV-2 seroprevalence in children and the evolution of clustering within classes and schools from June to November, 2020, in a prospective cohort study of school children in the canton of Zurich, Switzerland.MethodsChildren from randomly selected schools and classes, stratified by district, were invited to participate in serological testing of SARS-CoV-2 in June-July and October-November 2020. Parents of children filled questionnaires on sociodemographic and health-related questions. 55 schools and 275 classes within them were enrolled, with 2603 children participating in the first, and 2552 in the second testing (age range 6-16 years). We evaluated longitudinal changes of seroprevalence in districts and investigated clustering of seropositive cases within classes and schools.ResultsOverall SARS-CoV-2 seroprevalence was 2.4% (95% CrI 1.4%-3.6%) in summer and 4.5% (95% CrI 3.2%-6.0%) in not previously seropositive children in late autumn, leading to estimated 7.8% (95% CrI 6.2%-9.5%) of ever seropositive children, without significant differences among lower, middle and upper school levels. Among the 2223 children with serology tested twice, 28 (40%) of previously seropositive were negative, and 109 (5%) previously negative became seropositive. Seroprevalence was not different between school levels or sexes, but varied across districts (1.7% to 15.0%). Between June-July and October-November 2020, the ratio of diagnosed to newly seropositive children was 1 to 8. At least one newly seropositive child was detected in 47 of 55 schools and 90 of 275 classes. Among 130 classes with high participation rate, 0, 1-2 or ≥3 seropositive children were present in 73 (56%), 50 (38%) and 7 (5%) classes, respectively. Class level explained slightly more variation of individual serological results (standard deviation of random effects (SD) 0.97) than school level (SD 0.61) in the multilevel logistic regression models. Symptoms were reported for 22% of seronegative and 29% of newly seropositive children since summer.ConclusionsUnder a regimen of open schools with some preventive measures in place since August, clustering of seropositive cases occurred in very few classes and not across entire schools despite a clear increase in seropositive children during a period of high transmission of SARS-CoV-2.Trial registrationClinicalTrials.gov NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717

BackgroundWe previously showed that the 10-year cardiovascular disease (CVD) risk threshold to initiate statins for primary prevention depends on the baseline CVD risk, age, sex, and the incidence of statin-related harm outcome and competing risk for non-CVD death. As these factors appear to vary across countries, we aimed in this study to determine country-specific thresholds and provide guidelines a quantitative benefit-harm assessment method for local adaptation.MethodsFor each of the 186 countries included, we replicated the benefit-harm balance analysis using an exponential model to determine the thresholds to initiate statin use for populations aged 40 to 75 years, with no history of CVD. The analyses took data inputs from a priori studies, including statin effect estimates (network meta-analysis), patient preferences (survey), and baseline incidence of harm outcomes and competing risk for non-CVD (global burden of disease study). We estimated the risk thresholds above which the benefits of statins were more likely to outweigh the harms using a stochastic approach to account for statistical uncertainty of the input parameters.ResultsThe 5thand 95thpercentiles of the 10-year risk thresholds above which the benefits of statins outweigh the harms across 186 countries ranged between 14 and 20% in men and 19–24% in women, depending on age (i.e., 90% of the country-specific thresholds were in the ranges stated). The median risk thresholds varied from 14 to 18.5% in men and 19 to 22% in women. The between-country variability of the thresholds was slightly attenuated when further adjusted for age resulting, for example, in a 5thand 95thpercentiles of 14–16% for ages 40–44 years and 17–21% for ages 70–74 years in men. Some countries, especially the islands of the Western Pacific Region, had higher thresholds to achieve net benefit of statins at 25–36% 10-year CVD risks.ConclusionsThis extensive benefit-harm analysis modeling shows that a single CVD risk threshold, irrespective of age, sex and country, is not appropriate to initiate statin use globally. Instead, countries need to carefully determine thresholds, considering the national or subnational contexts, to optimize benefits of statins while minimizing related harms and economic burden.

Introduction: The ERS/ATS technical standards on field walking tests (2014) suggest to continuously measure oxygen saturation (SpO2) during a six-minute walk test (6MWT), while walking behind the patient. However, its impact on walking distance remains unclear. Methods: We conducted a randomized cross-over study to evaluate the impact of walking walking behind the patient during the 6MWT vs. standing aside. At the end of a pulmonary rehabilitation programme, each patient performed two 6MWTs in random order and separated by 30min’s rest. Results: 49 COPD patients (GOLD II-IV) were included. In a regression model adjusting for patient and period, walking behind the patient during the 6MWT resulted in a lower walking distance (mean difference -9.1 m, [95%CI, -13.9 to -4.3], p Method: Although we observed highly statistically significant differences between the two experimental conditions on a study population level, the observations may not be considered clinically relevant given the well-established MID of 30m in COPD. However, for individual patients, unaccompanied walking results in a substantially higher walking distance.

Background The adoption of mHealth technology in travel medicine is a relatively new and unexplored field. We have further developed a TRAVEL application (app) for real-time data monitoring during travel. In this manuscript we report on the feasibility using this new app in a large and diverse cohort of travellers to three continents. Methods We enrolled 1000 participants from the travel clinics of Zurich and Basel, Switzerland, aged ≥18 years, travelling to Thailand, India, China, Tanzania, Brazil and Peru between 09/2017–01/2019. Participants included healthy travellers, individuals with pre-existing chronic diseases and elderly travellers (≥60 years). Participants completed an app-based daily survey on risk behaviours/health incidents pre-, during and after travel. Simultaneously, GPS locations were tightly collected and linked to environmental data. Results 793 (79%) travellers answered at least one questionnaire during their trip. Participants’ median age was 34 years (range 18–84 years); 8% were aged ≥60 years; 55% female; 32% had pre-existing chronic diseases. Completion rates were similar in younger and elderly travellers and in those with and without pre-existing diseases. Conclusions The use of a smartphone app is a feasible method for collecting behavioural and health data in elderly travellers and individuals with chronic diseases travelling to three continents.

AIMS OF THE STUDY The impact of coronavirus disease 2019 (COVID-19) on patients listed for solid organ transplantation has not been systematically investigated to date. Thus, we assessed occurrence and effects of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients on the Swiss national waiting list for solid organ transplantation. METHODS Patient data were retrospectively extracted from the Swiss Organ Allocation System (SOAS). From 16 March to 31 May 2020, we included all patients listed for solid organ transplantation on the Swiss national waiting list who were tested positive for SARS-CoV-2. Severity of COVID-19 was categorised as follows: stage I, mild symptoms; stage II, moderate to severe symptoms; stage III, critical symptoms; stage IV, death. We compared the incidence rate (laboratory-confirmed cases of SARS-CoV-2), the hospital admission rate (number of admissions of SARS-CoV-2-positive individuals), and the case fatality rate (number of deaths of SARS-CoV-2-positive individuals) in our study population with the general Swiss population during the study period, calculating age-adjusted standardised incidence ratios and standardised mortality ratios, with 95% confidence intervals (CIs). RESULTS A total of 1439 patients were registered on the Swiss national solid organ transplantation waiting list on 31 May 31 2020. Twenty-four (1.7%) waiting list patients were reported to test positive for SARS-CoV-2 in the study period. The median age was 56 years (interquartile range 45.3–65.8), and 14 (58%) were male. Of all patients tested positive for SARS-CoV-2, two patients were asymptomatic, 14 (58%) presented in COVID-19 stage I, 3 (13%) in stage II, and 5 (21%) in stage III. Eight patients (33%) were admitted to hospital, four (17%) required intensive care, and three (13%) mechanical ventilation. Twenty-two patients (92%) of all those infected recovered, but two male patients aged >65 years with multiple comorbidities died in hospital from respiratory failure. Comparing our study population with the general Swiss population, the age-adjusted standardised incidence ratio was 4.1 (95% CI 2.7–6.0). CONCLUSION The overall rate of SARS-CoV-2 infections in candidates awaiting solid organ transplantation was four times higher than in the Swiss general population; however, the frequency of testing likely played a role. Given the small sample size of affected patients, conclusions have to be drawn cautiously and results need verification in larger cohorts.

Background Despite physical activity (PA) being recognized as a critically important factor for good physical and mental health already early in life and throughout the life course, prospective data on activity behavior during the preschool years remains scarce. This study examined trajectories and determinants of levels and change in total PA (TPA), moderate-to-vigorous PA (MVPA) and sedentary behavior (SB) in a representative sample of Swiss preschoolers. Methods Data were drawn from the Swiss Preschoolers’ Health Study (SPLASHY), a multi-site prospective cohort study including 555 children (53% boys) aged 2-to-6 years at baseline. A follow-up was conducted after 12 months. Activity behavior was measured using accelerometers. Information on 35 potential determinants from different socio-ecological domains was either directly measured or parent-reported. Trajectories of TPA, MVPA and SB over time were described for boys and girls. Linear mixed models were used to investigate factors that predicted levels and change in TPA, MVPA and SB. Results All children were sufficiently physically active according to published recommendations for preschoolers. Trajectory profiles revealed a marked increase in TPA and MVPA in boys and girls whereas SB remained fairly stable over time. Mixed modeling demonstrated that variables most relevant to determining PA levels were sex, age and activity temperament (all positively associated). Together with gross motor skills, birth weight, family structure (only for TPA) and season (only for MVPA), these factors accounted for 26 and 32% of total variance explained in TPA and MVPA, respectively. Activity temperament emerged as the strongest determinant of SB (negative association) and explained with sex, season and family structure 20% of total variance in SB. The presence of older siblings was the only factor that predicted change in PA over time. Conclusions In this healthy physically active cohort of preschoolers, non-modifiable individual-level factors had the greatest influence on PA. The limited success of this and previous studies to identify modifiable determinants and the finding that most preschoolers were sufficiently active suggest that future attempts should provide insights into how preschoolers’ activity levels can be maintained and fostered to prevent subsequent harmful declines attributable, amongst others, to educational transitions. Thus, good-quality longitudinal studies are needed. Trial registration Current Controlled Trials ISRCTN41045021 (date of registration: 21.03.14). Electronic supplementary material The online version of this article (10.1186/s12966-018-0670-8) contains supplementary material, which is available to authorized users.

Background Several cross-sectional and short-term studies suggest that patient-reported outcomes (PROs) may be useful to help predict COPD exacerbations, but evidence from long-term prospective cohort studies is lacking. Our aim was to assess if PROs add to the prediction of exacerbations. Methods Four hundred eight primary care patients with COPD participated in the multicenter prospective International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) study. PROs included the Chronic Respiratory Disease Questionnaire, the Hospital Anxiety and Depression Scale, the Feeling Thermometer, and the LASA Physical Activity Questionnaire (LAPAQ). Exacerbations during 4½ years were adjudicated by experts. We used negative binomial regression to assess the association between PROs and exacerbations while considering age, sex, airflow obstruction, previous exacerbations, and smoking status. We then assessed if adding PROs improved the predictive properties of widely used indices. Results Lower levels of dyspnea, fatigue, and anxiety and higher levels of physical activity were associated with a lower risk of exacerbations (adjusted incidence rate ratio [IRR], 0.90; 95% CI, 0.84-0.97; P = .01; IRR, 0.93; 95% CI, 0.86-1.00; P = .04; IRR, 1.03; 95% CI, 1.00-1.06; P = .03; IRR, 0.93; 95% CI, 0.87-0.99; P = .04, respectively). The best prediction was when LAPAQ was added to the BMI, airflow obstruction, dyspnea, and previous exacerbations (BODEx) index (area under the curve Δ+0.02, from 0.72-0.74). However, this increase was not clinically relevant (net reclassification improvement, 0.03; 95% CI, −0.03 to 0.08). Conclusions Some domains of PROs are independently associated with exacerbations but do not lead to clearly improved prediction when added to established indices to predict exacerbations. There is still much room for improvement in the prediction of exacerbations. Trial Registry ClinicalTrials.gov; No.: NCT00706602.

Background and objective Daily physical activity (PA) is reduced in patients with COPD. Previous cross-sectional analyses indicate various predictors for a low level of PA including airway obstruction, exacerbations and co-morbidities. However, information from longitudinal studies evaluating PA in the context of disease progression, survival and co-morbidities is scant. Methods In a heterogeneous cohort of COPD patients, we annually assessed the number of steps per day over 1 week and potential determinants including lung function, exacerbations and co-morbidities. Univariable and multivariable mixed effect models were used to investigate associations between the change in steps per day (dependent variable) and possible predictors and their annual changes. Results A total of 177 COPD patients (46% GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 1/2, 38% stage 3 and 16% stage 4) with a mean (min/max) follow-up time of 2.7 (1/5) years were annually assessed. The number of steps per day decreased significantly over time (P

Summary Pharmacotherapy represents a desirable potential therapeutic alternative for patients with obstructive sleep apnoea (OSA). We aimed to summarize evidence on the efficacy of pharmacotherapy in adults with OSA and delineate the underlying mechanisms. Seven databases were systematically screened for randomised controlled trials (RCTs) from their inception to September 2018. According to a pre-registered study protocol (PROSPERO-ID-CRD42018086446) network meta-analysis was performed to obtain intervention effects on the apnoea-hypopnoea-index (AHI) based on data extracted from published reports. We identified 58 RCTs (n = 1710 patients) investigating 44 different drugs or drug-combinations. Interventions were classified into seven pathomechanism-groups and summarized narratively. A meta-analysis of 17 trials for seven drugs (acetazolamide, donepezil, mirtazapine, ondansetron, paroxetine, protriptyline, theophylline) indicated a small effect for acetazolamide (mean difference in AHI −9.6/h [−17.7; −1.4]; p = 0.02). In the network meta-analysis (I2 = 50%) nine drugs (tramazoline, liraglutide, spironolactone/furosemide, acetazolamide, dronabinol, zonisamide, phentermine, spironolactone, and ondansetron/fluoxetine) significantly lowered the AHI compared to placebo. Although some trials indicate favorable outcomes, these results are only valid for distinctive OSA-phenotypes or were not clinically significant. The effect sizes were small, the majority of trials were not adequately powered. There is currently insufficient evidence to recommend any pharmacotherapy for OSA and no phase-III trials are available.

Background: Continuous positive airway pressure (CPAP) is currently the treatment of choice for sleepiness in patients with obstructive sleep apnea (OSA), however, adherence is often thought to be suboptimal. We investigated the effects of suboptimal CPAP-usage on sleepiness parameters in patients with OSA. Methods: In this 2-week, parallel, double-blind, randomized controlled trial we enrolled moderate-to-severe OSA patients with excessive pre-treatment daytime sleepiness (ESS score >10) who had suboptimal CPAP adherence over at least 12 months (mean nightly usage time 3-4 hours). Patients were allocated through minimization to either CPAP-withdrawal (sham-CPAP) or continuation of CPAP (therapeutic-CPAP). A Bayesian analysis with historical priors calculated the posterior probability of superiority. Findings: Between May 27, 2016 and November 10, 2018, 57 patients (60±8 years, 79% men, 93% Caucasian) were allocated in total, and 52 who completed the study (50% in each arm) were included in the final analysis. The unadjusted ESS-score increase was +2.9 points (95% CI +1.3 to +4.7; p=0.001) in the sham-CPAP-group when compared to continuing therapeutic CPAP. The probability of superiority of therapeutic CPAP over sham CPAP was 97.6% for ESS, 90.1% for systolic, and 80.3% for diastolic blood pressure. Conclusion: Patients with moderate-to-severe OSA and daytime sleepiness are still getting a substantial benefit from suboptimal CPAP adherence, albeit not as much as they might get if they adhered more. Whether a similar statement can be made for even lower adherence levels remains to be established in future trials. Trial Registration Number: The trial was pre-registered at ClinicalTrials.gov (NCT02781740) Funding Statement: Swiss National Science Foundation (grant no. 32003B_162534). Declaration of Interests: JRS reports personal fees from Resmed UK, personal fees from Bayer Germany, outside the submitted work. MK reports grants from University of Zurich, grants from Lunge Zurich, during the conduct of the study; grants from Bayer AG, outside the submitted work. TG reports personal fees from Bayer AG, outside the submitted work. All other authors report no conflict of interest. Ethics Approval Statement: All tests were conducted by the University Hospital Zurich and approved by the cantonal ethics committee of Zurich (KEK-ZH-Nr. 2016-00332). All patients provided written informed consent according to the Declaration of Helsinki. Data were obtained according to Good Clinical Practice (GCP) guidelines.

Background: Central sleep apnoea/Cheyne Stokes Respiration (CSA/CSR) in heart failure is associated with an impaired prognosis. Continuous positive airway pressure (CPAP) and adaptive servo-ventilation (ASV) as well as nocturnal oxygen (O2) are treatment modalities for CSA/CSR. Whether treatment of CSA/CSR is beneficial is controversial. Aims: Assess the effect of treatment of CSA/CSR on cardiac function in heart failure. Methods: Databases were searched up to Dec 2017 for randomised controlled trials (RCTs) comparing the effect of any combination of CPAP, ASV, O2 or an inactive control on left ventricular ejection fraction (LVEF) in patients with heart failure and CSA/CSR. A network meta-analysis (multivariate random-effects meta-regression) was performed. Results: 16 RCTs (951 patients; apnoea-hypopnoea-index 38±3/h, LVEF 29±3%) were included. Compared to inactive control, both CPAP and ASV significantly improved LVEF by 4.4% (95%CI 0.3-8.5%, p=0.036) and 3.8% (95%CI 0.6-7.0%, p=0.025), respectively, whereas O2 had no effect on LVEF (p=0.35). There was no difference between CPAP and ASV (p=0.76). The treatment effect of positive pressure ventilation was larger when baseline LVEF was lower in systolic heart failure. Conclusions: CPAP and ASV are effective in improving LVEF in patients with heart failure and CSA/CSR, whereas O2 is not. There is no difference in the effect on LVEF between CPAP and ASV.