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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.

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.

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.