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Objective: To assess the associations between parents’ working conditions during the lockdown period (March-May 2020) and children’s health-related quality of life (HRQOL) over the first year of the COVID-19 pandemic in Zurich, Switzerland. Methods: We included 2211 children (6–16 years) and their parents from the prospective study Ciao Corona. Parents reported their employment status and working conditions during the lockdown. Children’s HRQOL was assessed in June-July 2020, January and March 2021 using the parents-report of the KINDL®. We used mixed models to assess the associations between parents’ working conditions and children’s HRQOL at the three time points. Results: Children from families in which at least one parent changed their working conditions during the lockdown showed lower HRQOL in June-July 2020, than children from families in which neither parent experienced changes. Children from families in which at least one parent had to work remotely continued to show lower HRQOL in January and March 2021. Conclusion: Changes in parents’ working conditions during lockdown were negatively associated with children’s HRQOL. Public health policies aiming to support families susceptible to adverse changes are needed., International Journal of Public Health, 67, ISSN:1661-8556, ISSN:1661-8564

Background Using the example of secondary prophylaxis of myocardial infarction (MI), our aim was to establish a framework for assessing cost consequences of compliance with clinical guidelines; thereby taking cost trajectories and cost distributions into account. Methods Swiss mandatory health insurance claims from 1840 persons with hospitalization for MI in 2014 were analysed. Included persons were predominantly male (74%), had a median age of 73 years, and 71% were pre-exposed to drugs for secondary prophylaxis, prior to index hospitalization. Guideline compliance was defined as being prescribed recommended 4-class drug prophylaxis including drugs from the following four classes: beta-blockers, statins, aspirin or P2Y12 inhibitors, and angiotension-converting enzyme inhibitors or angiotensin receptor blockers. Health care expenditures (HCE) accrued over 1 year after index hospitalization were compared by compliance status using two-part regression, trajectory analysis, and counterfactual decomposition analysis. Results Only 32% of persons received recommended 4-class prophylaxis. Compliant persons had lower HCE (− 4865 Swiss Francs [95% confidence interval − 8027; − 1703]) and were more likely to belong to the most favorable HCE trajectory (with 6245 Swiss Francs average annual HCE and comprising 78% of all studied persons). Distributional analyses showed that compliance-associated HCE reductions were more pronounced among persons with HCE above the median. Conclusions Compliance with recommended prophylaxis was robustly associated with lower HCE and more favorable cost trajectories, but mainly among persons with high health care expenditures. The analysis framework is easily transferrable to other diseases and provides more comprehensive information on HCE consequences of non-compliance than mean-based regressions alone. Supplementary Information The online version contains supplementary material available at 10.1186/s12913-020-05985-x.

BackgroundMuch 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 co-hort studies exist. Vaccination of children, initiated at different times for different age groups, adds additional complexity to understand how seroprevalence developed in the school aged population.AimWe 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.MethodsIn 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 sero-prevalence in a class and summarized as median (interquartile range).Results1875 children from 287 classes in 43 schools were tested, with median age 12 (range 6-17), 51% 12+ vaccinated. Seroprevalence increased from 5.6% (95% CrI: 3.5-7.6%) to 31.1% (27.0-36.1%) in unvaccinated children, and 46.4% (42.6-50.9%) in all children (including vaccinated). Earlier in the pandemic, seropositivity rates in primary schools were similar to or slightly higher (ConclusionSeroprevalence 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.Trial Registration:ClinicalTrials.govNCT04448717

Supplemental material, sj-docx-1-hme-10.1177_23333928221097741 for Small Area Variation of Adherence to Clinical Recommendations: An Example from Switzerland by Oliver Gruebner, Wenjia Wei, Agne Ulyte, Viktor von Wyl, Holger Dressel, Beat Brüngger, Caroline Bähler, Eva Blozik and Matthias Schwenkglenks in Health Services Research and Managerial Epidemiology

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.

Background T1‐weighted dynamic contrast‐enhanced (DCE) perfusion magnetic resonance imaging (MRI) has been broadly utilized in the evaluation of brain tumors. We aimed at assessing the diagnostic accuracy of DCE‐MRI in discriminating between low‐grade gliomas (LGGs) and high‐grade gliomas (HGGs), between tumor recurrence and treatment‐related changes, and between primary central nervous system lymphomas (PCNSLs) and HGGs. Methods We performed this study based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis of Diagnostic Test Accuracy Studies criteria. We systematically surveyed studies evaluating the diagnostic accuracy of DCE‐MRI for the aforementioned entities. Meta‐analysis was conducted with the use of a random effects model. Results Twenty‐seven studies were included after screening of 2945 possible entries. We categorized the eligible studies into three groups: those utilizing DCE‐MRI to differentiate between HGGs and LGGs (14 studies, 546 patients), between recurrence and treatment‐related changes (9 studies, 298 patients) and between PCNSLs and HGGs (5 studies, 224 patients). The pooled sensitivity, specificity, and area under the curve for differentiating HGGs from LGGs were 0.93, 0.90, and 0.96, for differentiating tumor relapse from treatment‐related changes were 0.88, 0.86, and 0.89, and for differentiating PCNSLs from HGGs were 0.78, 0.81, and 0.86, respectively. Conclusions Dynamic contrast‐enhanced‐Magnetic resonance imaging is a promising noninvasive imaging method that has moderate or high accuracy in stratifying gliomas. DCE‐MRI shows high diagnostic accuracy in discriminating between HGGs and their low‐grade counterparts, and moderate diagnostic accuracy in discriminating recurrent lesions and treatment‐related changes as well as PCNSLs and HGGs., Dynamic contrast‐enhanced‐Magnetic resonance imaging has high diagnostic accuracy in grading gliomas and moderate accuracy in surveillance of high‐grade gliomas and differentiation from primary central nervous system lymphomas. DCE‐MRI is a promising noninvasive imaging technique in diagnosing different types of brain tumors.

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.

Although long COVID in children exists, it is still unclear to what extent children are affected. The Ciao Corona study is a longitudinal cohort investigating SARS-CoV-2 seroprevalence and clustering of cases among around 2500 children and adolescents (hereafter referred to as children) from 55 randomly selected primary and secondary schools in the canton of Zurich in Switzerland. Between June 2020 and April 2021, we completed three testing phases where we collected venous blood for serological analysis and asked about symptoms with online questionnaires. We compared children who tested positive for SARS-CoV-2 antibodies in October/November 2020 with those who tested negative. Children who were seronegative in October/November 2020 and seroconverted or were not retested in March/April 2021 were excluded from the analysis (n=256). In March-May 2021 we assessed the presence of symptoms occurring since October 2020, lasting for at least 4 weeks, and persisting for either >4 weeks or >12 weeks. Overall, 1355 of 2503 children with a serology result in October/November 2020 and follow up questionnaire in March-May 2021 were included. Among seropositive and seronegative 6-to 16-year-old children, 9% versus 10% reported at least one symptom beyond 4 weeks, and 4% versus 2% at least one symptom beyond 12 weeks. None of the seropositive children reported hospitalization after October 2020. This study suggests a low prevalence of symptoms compatible with long COVID in a randomly selected population-based cohort of children followed over 6 months after serological testing.

Objectives When research evidence is lacking, patient and provider preferences, expected to vary geographically, might have a stronger role in clinical decisions. We investigated whether the strength or the direction of recommendation is associated with the degree of geographic variation in utilisation. Design In this cross-sectional study, we selected 24 services following a comprehensive approach. The strength and direction of recommendations were assessed in duplicate. Multilevel models were used to adjust for demographic and clinical characteristics and estimate unwarranted variation. Setting Observational study of claims to mandatory health insurance in Switzerland in 2014. Participants Enrolees eligible for the 24 healthcare services. Primary outcome measures The variances of regional random effects, also expressed as median odds ratios (MOR). Services grouped by strength and direction of recommendations were compared with Welch’s t-test. Results The sizes of the eligible populations ranged from 1992 to 409 960 patients. MOR ranged between 1.13 for aspirin in secondary prevention of myocardial infarction to 1.68 for minor surgical procedures performed in inpatient instead of outpatient settings. Services with weak recommendations had a negligibly higher variance and MOR (difference in means (95% CI) 0.03 (−0.06 to 0.11) and 0.05 (−0.11 to 0.21), respectively) compared with strong recommendations. Services with negative recommendations had a slightly higher variance and MOR (difference in means (95% CI) 0.07 (−0.03 to 0.18) and 0.14 (−0.06 to 0.34), respectively) compared with positive recommendations. Conclusions In this exploratory study, the geographical variation in the utilisation of services associated with strong vs weak and negative vs positive recommendations was not substantially different, although the difference was somewhat larger for negative vs positive recommendations. The relationships between the strength or direction of recommendations and the variation may be indirect or modified by other characteristics of services. As initiatives discouraging low-value care are gaining attention worldwide, these findings may inform future research in this area.

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

Variation in utilization of healthcare services is influenced by patient, provider and healthcare system characteristics. It could also be related to the evidence supporting their use, as reflected in the availability and strength of recommendations in clinical guidelines. In this study, we analyzed the geographic variation of colorectal, breast and prostate cancer screening utilization in Switzerland and the influence of available guidelines and different modifiers of access. Colonoscopy, mammography and prostate specific antigen (PSA) testing use in eligible population in 2014 was assessed with administrative claims data. We ran a multilevel multivariable logistic regression model and calculated Moran’s I and regional level median odds ratio (MOR) statistics to explore residual geographic variation. In total, an estimated 8.1% of eligible persons received colonoscopy, 22.3% mammography and 31.3% PSA testing. Low deductibles, supplementary health insurance and enrollment in a managed care plan were associated with higher screening utilization. Cantonal breast cancer screening programs were also associated with higher utilization. Spatial clustering was observed in the raw regional utilization of all services, but only for prostate cancer screening in regional residuals of the multilevel model. MOR was highest for prostate cancer screening (1.24) and lowest for colorectal cancer screening (1.16). The reasons for the variation of the prostate cancer screening utilization, not recommended routinely without explicit shared decision-making, could be further investigated by adding provider characteristics and patient preference information. This first cross-comparison of different cancer screening patterns indicates that the strength of recommendations, mediated by specific health policies facilitating screening, may indeed contribute to variation.

Background Observational studies of influenza vaccination are criticized as flawed due to unmeasured confounding. The goal of this cohort study was to explore the value and role of secondary claims data to inform the effectiveness of influenza vaccination, while systematically trying to reduce potential bias. Methods We iteratively reviewed the components of the PICO approach to refine study design. We analyzed Swiss mandatory health insurance claims of adult patients with chronic diseases, for whom influenza vaccination was recommended in 2014. Analyzed outcomes were all-cause mortality, hospitalization with a respiratory infection or its potential complication, and all-cause mortality after such hospitalization, adjusting for clinical and health care use variables. Cox and multi-state models were applied for time-to-event analysis. Results Of 343,505 included persons, 22.4% were vaccinated. Vaccinated patients were on average older, had more morbidities, higher health care expenditures, and had been more frequently hospitalized. In non-adjusted models, vaccination was associated with increased risk of events. Adding covariates decreased the hazard ratio (HR) both for mortality and hospitalizations. In the full model, the HR [95% confidence interval] for mortality during season was 0.82 [0.77–0.88], and closer to null effect after season. In contrast, HR for hospitalizations was increased during season to 1.28 [1.15–1.42], with estimates closer to null effect after season. HR in multi-state models were similar to those in the single-outcome models, with HR of mortality after hospitalization negative both during and after season. Conclusion In patients with chronic diseases, influenza vaccination was associated with more frequent specific hospitalizations, but decreased risk of mortality overall and after such hospitalization. Our approach of iteratively considering PICO elements helped to consider various sources of bias in the study sequentially. The selection of appropriate, specific outcomes makes the link between intervention and outcome more plausible and can reduce the impact of confounding.

Objectives Indicators of guideline adherence are frequently used to examine the appropriateness of healthcare services. Only some potential indicators are actually usable for research with routine administrative claims data, potentially leading to a biased selection of research questions. This study aimed at developing a systematic approach to extract potential indicators from clinical practice guidelines (CPG), evaluate their feasibility for research with claims data and assess how the extracted set reflected different types of healthcare services. Diabetes mellitus (DM), Swiss national guidelines and health insurance claims data were analysed as a model case. Methods CPG for diabetes patients were retrieved from the Swiss Endocrinology and Diabetes Society website. Recommendation statements involving a specific healthcare intervention for a defined patient population were translated into indicators of guideline adherence. Indicators were classified according to disease stage and healthcare service type. We assessed for all indicators whether they could be analysed with Swiss mandatory health insurance administrative claims data. Results A total of 93 indicators were derived from 15 CPG, representing all sectors of diabetes care. For 63 indicators, the target population could not be identified using claims data only. For 67 indicators, the intervention could not be identified. Nine (10%) of all indicators were feasible for research with claims data (three addressed gestational diabetes and screening, five screening for complications and one glucose measurement). Some types of healthcare services, eg, management of risk factors, treatment of the disease and secondary prevention, lacked corresponding indicators feasible for research. Conclusions Our systematic approach could identify a number of indicators of healthcare service utilisation, feasible for DM research with Swiss claims data. Some areas of healthcare were covered less well. The approach could be applied to other diseases and countries, helping to identify the potential bias in the selection of indicators and optimise research.

Background We examined colorectal, breast, and prostate cancer screening utilization in eligible populations within three data cross-sections, and identified factors potentially modifying cancer screening utilization in Swiss adults. Methods The study is based on health insurance claims data of the Helsana Group. The Helsana Group is one of the largest health insurers in Switzerland, insuring approximately 15% of the entire Swiss population across all regions and age groups. We assessed proportions of the eligible populations receiving colonoscopy/fecal occult blood testing (FOBT), mammography, or prostate-specific antigen (PSA) testing in the years 2014, 2016, and 2018, and calculated average marginal effects of individual, temporal, regional, insurance-, supply-, and system-related variables on testing utilization using logistic regression. Results Overall, 8.3% of the eligible population received colonoscopy/FOBT in 2014, 8.9% in 2016, and 9.2% in 2018. In these years, 20.9, 21.2, and 20.4% of the eligible female population received mammography, and 30.5, 31.1, and 31.8% of the eligible male population had PSA testing. Adjusted testing utilization varied little between 2014 and 2018; there was an increasing trend of 0.8% (0.6–1.0%) for colonoscopy/FOBT and of 0.5% (0.2–0.8%) for PSA testing, while mammography use decreased by 1.5% (1.2–1.7%). Generally, testing utilization was higher in French-speaking and Italian-speaking compared to German-speaking region for all screening types. Cantonal programs for breast cancer screening were associated with an increase of 7.1% in mammography utilization. In contrast, a high density of relevant specialist physicians showed null or even negative associations with screening utilization. Conclusions Variation in cancer screening utilization was modest over time, but considerable between regions. Regional variation was highest for mammography use where recommendations are debated most controversially, and the implementation of programs differed the most.

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).

This cohort study reports the prevalence of long-term symptoms in children and adolescents who had recovered from acute SARS-CoV-2 infection.

BackgroundSwitzerland had one of the highest incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Europe during the second wave. Schools were open as in most of Europe with specific preventive measures in place. However, the frequency and transmission of acute unrecognized, asymptomatic or oligosymptomatic infections in schools during this time of high community transmission is unknown. Thereof, our aim was to pilot a surveillance system that detects acute SARS-CoV-2 infections in schools and possible transmission within classes.Methods14 out of the randomly selected sample of the Ciao Corona cohort study participated between December 1 and 11, a time when incidence rate for SARS-CoV-2 infections was high for the canton of Zurich. We determined point-prevalence of acute SARS-CoV-2 infections of school children attending primary and secondary school. A buccal swab for polymerase chain reaction (PCR) and a rapid diagnostic test (RDT) to detect SARS-CoV-2 were taken twice 1 week apart (T1 and T2) in a cohort of children from randomly selected classes. A questionnaire assessed demographics and symptoms compatible with a SARS-CoV-2 infection during the past 5 days.ResultsOut of 1299 invited children, 641 (49%) 6- to 16-year-old children and 66 teachers from 14 schools and 67 classes participated in at least 1 of 2 testings. None of the teachers but 1 child had a positive PCR at T1, corresponding to a point-prevalence in children of 0.2% (95% CI 0.0% to 1.1%), and no positive PCR was detected at T2. The child with positive PCR at T1 was negative on the RDT at T1 and both tests were negative at T2. There were 7 (0.6%) false positive RDTs in children and 2 (1.7%) false positive RDTs in teachers at T1 or T2 among 5 schools (overall prevalence 0.7%). All 9 initially positive RDTs were negative in a new buccal sample taken 2 hours to 2 days later, also confirmed by PCR. 35% of children and 8% of teachers reported mild symptoms during the 5 days prior to testing.ConclusionIn a setting of high incidence of SARS-CoV-2 infections, unrecognized virus spread within schools was very low. Schools appear to be safe with the protective measures in place (e.g., clearly symptomatic children have to stay at home, prompt contact tracing with individual and class-level quarantine, and structured infection prevention measures in school). Specificity of the RDT was within the lower boundary of performance and needs further evaluation for its use in schools. Given the low point prevalence even in a setting of very high incidence, a targeted test, track, isolate and quarantine (TTIQ) strategy for symptomatic children and school personnel adapted to school settings is likely more suitable approach than surveillance on entire classes and schools.Trial registrationClinicalTrials.govNCT04448717https://clinicaltrials.gov/ct2/show/NCT04448717

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