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Dominik Menges,1 Michela C Piatti,1 Thomas Cerny,2,3 Milo A Puhan1 1Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland; 2Foundation Board, Cancer Research Switzerland (Krebsforschung Schweiz KFS), Bern, Switzerland; 3Human Medicines Expert Committee (HMEC), Swissmedic, Bern, SwitzerlandCorrespondence: Dominik Menges, Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Hirschengraben 84, Zurich, CH-8001, Switzerland, Tel +41 44 634 46 15, Email dominik.menges@uzh.chBackground: Patient preference studies can inform decision-making across all stages of the medical product life cycle (MPLC). The treatment landscape for advanced prostate cancer (APC) treatment has substantially changed in recent years. However, the most patient-relevant aspects of APC treatment remain unclear. This systematic review of patient preference studies in APC aimed to summarize the evidence on patient preferences and patient-relevant aspects of APC treatments, and to evaluate the potential contribution of existing studies to decision-making within the respective stages of the MPLC.Methods: We searched MEDLINE and EMBASE for studies evaluating patient preferences related to APC treatment up to October 2020. Two reviewers independently performed screening, data extraction and quality assessment in duplicate. We descriptively summarized the findings and analyzed the studies regarding their contribution within the MPLC using an analytical framework.Results: Seven quantitative preference studies were included. One study each was conducted in the marketing approval and the health technology assessment (HTA) and reimbursement stage, and five were conducted in the post-marketing stage of the MPLC. While almost all stated to inform clinical practice, the specific contributions to clinical decision-making remained unclear for almost all studies. Evaluated attributes related to benefits, harms, and other treatment-related aspects and their relative importance varied relevantly between studies. All studies were judged of high quality overall, but some methodological issues regarding sample selection and the definition of patient-relevant treatment attributes were identified.Conclusion: The most patient-relevant aspects regarding the benefits and harms of APC treatment are not yet established, and it remains unclear which APC treatments are preferred by patients. Findings from this study highlight the importance of transparent reporting and discussion of study findings according to their aims and with respect to their stage within the MPLC. Future research may benefit from using the MPLC framework for analyzing or determining the aims and design of patient preference studies.Keywords: patient preferences, medical product life cycle, preference research, benefit-harm assessment, patient-centered care, prostate cancer, systematic review

Abstract Background Craving for alcohol is a highly controversial subjective construct and may be clarified by Loewenstein's visceral theory, which emphasizes craving's behavioral effects on the relative value of alcohol. Based on the visceral theory, this study examined the effects of a craving induction on the relative value of alcohol as measured by a behavioral choice task. In addition, based on previous evidence of its role in the expression of craving, the influence of DRD4 VNTR genotype (DRD4-L vs. DRD4-S) was also examined. Methods Thirty-five heavy drinkers (54% male; 31% DRD4-L) were randomly assigned to receive either a craving induction (exposure to personally relevant alcohol cues) or a control induction (exposure to neutral cues), which was followed by an alcohol-money choice task. Participants were assessed for craving and positive/negative affect throughout the procedure, and relative value of alcohol was derived from participant choices for alcohol versus money. DRD4 VNTR status was assessed retrospectively via buccal samples using previously established protocols. Results Factorial analysis of the craving induction revealed that it was associated with significant increase in craving (p < .001), but not greater relative value of alcohol. Factorial analyses including DRD4 VNTR genotype of did not suggest an influence on reactivity to the craving induction, although this analysis was substantially compromised by small cell sample sizes. Continuous analyses revealed that craving was significantly associated with the relative value of alcohol (p < .05) and possession of the DRD4-L allele further amplified this relationship (p < .001). Conclusion These results are interpreted as generally supporting Loewenstein's visceral theory of craving and evidence of a functional role of DRD4 VNTR genotype in the expression of craving for alcohol. Methodological limitations, mechanisms underlying these findings, and future directions are discussed.

Background/Objectives: This study aims to investigate differences in cancer diagnosis based on absolute case numbers and age-standardized incidence rate ratios (IRRs) in the pre-Coronavirus disease 2019 (COVID-19) years (2018/19) and the first two years of the COVID-19 pandemic (2020, 2021) in two Swiss cantons. Methods : Data of the Swiss cantonal cancer registry of the cantons of Zurich (ZH) and Zug (ZG) were used to descriptively investigate differences in annual and monthly absolute numbers regarding all-cancer and the five most common cancer types. Directly age-standardized monthly incidence rates (IRs) were calculated. Multivariate Quasipoisson regression models were fitted to determine the IRRs with 95% confidence intervals (95% CI). Results : Annual absolute numbers of all investigated cancers were similar in 2018/19, 2020, and 2021, except for prostate cancer (increase of 20.8% in 2021 compared to 2018/19). In 2020, there were generally more cancer diagnoses in January and February followed by a decrease in April and May. Compared to the pre-COVID-19 period, lower IRs were observed in 2020 for all-cancer (IRR = 0.96 [95% CI 0.96, 0.97]) and female breast cancer (0.92 [0.89, 0.96]), whereas higher IRs were observed in 2021 for all-cancer (1.02 [1.02, 1.02]) and prostate cancer (1.23 [1.18, 1.28]). Conclusions : Cancer detection and diagnoses decreased during the first year of the pandemic, especially during the most stringent lockdown phase in April. The findings of this study may inform the decisions of policymakers and public health system during future pandemics.

Objectives: Before vaccines and effective treatments were available, quarantine of close contacts was important to limit the spread of SARS-CoV-2. To evaluate potential benefits and harms of quarantine, we aimed to estimate infection rates and describe experiences and mental health among persons in mandated quarantine during the early SARS-CoV-2 pandemic., Methods: We invited adults in mandated quarantine after an exposure to SARS-CoV-2 identified through contact tracing of the Canton of Zurich, Switzerland, between August 2020 and January 2021. Participants completed two questionnaires and received up to two SARS-CoV-2 polymerase chain reaction tests, during and at the end of quarantine., Results: Among 395 participants, quarantine duration ranged from 2 to 20 days. By day 11 since the last contact, 11.1% [95% CI 8.4%-14.7%] were infected with SARS-CoV-2. The proportion of participants with symptoms of depression doubled from 9.3% before quarantine to 18.9% during quarantine, and 12.1% reported quarantine was very or extremely difficult., Conclusion: Although quarantine was only moderately burdensome for most participants, some experienced significant difficulties and burden. Policymakers need to balance infection control with potential harms placed on individuals., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Aschmann, Domenghino, Jung, Ballouz, Menges, Fehr and Puhan.)

Background: Breast cancer and frailty frequently co-occur in older women, and frailty status has been shown to predict negative health outcomes. However, the extent to which frailty assessments are utilized in observational research for the older breast cancer population is uncertain. Therefore, the aim of this review was to determine the frequency of use of frailty assessments in studies investigating survival or mortality, and characterize them, concentrating on literature from the past 5 years (2017-2022)., Methods: MEDLINE, EMBASE and Cochrane Library were systematically queried to identify observational studies (case-control, cohort, cross-sectional) published from 2017-2022 that focus on older females (≥ 65 years) diagnosed with breast cancer, and which evaluate survival or mortality outcomes. Independent reviewers assessed the studies for eligibility using Covidence software. Extracted data included characteristics of each study as well as information on study design, study population, frailty assessments, and related health status assessments. Risk of bias was evaluated using the appropriate JBI tool. Information was cleaned, classified, and tabulated into review level summaries., Results: In total, 9823 studies were screened for inclusion. One-hundred and thirty studies were included in the final synthesis. Only 11 (8.5%) of these studies made use of a frailty assessment, of which 4 (3.1%) quantified frailty levels in their study population, at baseline. Characterization of frailty assessments demonstrated that there is a large variation in terms of frailty definitions and resulting patient classification (i.e., fit, pre-frail, frail). In the four studies that quantified frailty, the percentage of individuals classified as pre-frail and frail ranged from 18% to 29% and 0.7% to 21%, respectively. Identified frailty assessments included the Balducci score, the Geriatric 8 tool, the Adapted Searle Deficits Accumulation Frailty index, the Faurot Frailty index, and the Mian Deficits of Accumulation Frailty Index, among others. The Charlson Comorbidity Index was the most used alternative health status assessment, employed in 56.9% of all 130 studies. Surprisingly, 31.5% of all studies did not make use of any health status assessments., Conclusion: Few observational studies examining mortality or survival outcomes in older women with breast cancer incorporate frailty assessments. Additionally, there is significant variation in definitions of frailty and classification of patients. While comorbidity assessments were more frequently included, the pivotal role of frailty for patient-centered decision-making in clinical practice, especially regarding treatment effectiveness and tolerance, necessitates more deliberate attention. Addressing this oversight more explicitly could enhance our ability to interpret observational research in older cancer patients., (© 2024. The Author(s).)

Introduction: Older patients are often deemed ineligible for clinical research, and many frequently-used endpoints and outcome measures are not as relevant for older patients for younger ones. This systematic review aimed to present an overview of outcomes used in clinical research regarding patients over the age of 65 years with prostate cancer., Materials and Methods: PubMed and Embase were systematically searched to identify studies on prostate cancer (treatment) in patients aged ≥65 between 2016 and 2023. Data on title, study design, number of participants and age, stage of disease, treatment, and investigated outcomes were synthesized and descriptively analyzed., Results: Sixty-eight studies were included. Of these most included patients over 65 years, while others used a higher age. Overall, 39 articles (57.3%) reported on survival-related outcomes, 22 (32.4%) reported on progression of disease and 38 (55.9%) used toxicity or adverse events as an outcome measure. Health-related quality of life and functional outcomes were investigated in 29.4%, and cognition in two studies. The most frequently investigated survival-related outcomes were overall and cancer-specific survival (51.3%); however, 38.5% only studied overall survival., Discussion: The main focus of studies included in this review remains survival and disease progression. There is limited attention for health-related quality of life and functional status, although older patients often prioritize the latter. Future research should incorporate outcome measures tailored to the aged population to improve care for older patients with prostate cancer., Competing Interests: Declaration of Competing Interest No conflict of interest for all authors., (Copyright © 2024. Published by Elsevier Ltd.)

Over a decade ago, the United States Preventive Services Taskforce (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer in all men, which considerably influenced prostate cancer screening policies worldwide after that. Consequently, the world has seen increasing numbers of advanced stages and prostate cancer deaths, which later led the USPSTF to withdraw its initial statement. Meanwhile, the European Union has elaborated a directive to address the problem of implementing prostate cancer screening in "Europe's Beating Cancer Plan". In Switzerland, concerned urologists formed an open Swiss Prostate Cancer Screening Group to improve the early detection of prostate cancer. On the 20th of September 2023, during the annual general assembly of the Swiss Society of Urology (SGU/SSU) in Lausanne, members positively voted for a stepwise approach to evaluate the feasibility of implementing organised prostate cancer screening programs in Switzerland. The following article will summarise the events and scientific advances in the last decade during which evidence and promising additional modalities to complement PSA-based prostate cancer screening have emerged. It also aims to provide an overview of contemporary strategies and their potential harms and benefits.

Background and Objective: Image-based artificial intelligence (AI) methods have shown high accuracy in prostate cancer (PCa) detection. Their impact on patient outcomes and cost effectiveness in comparison to human pathologists remains unknown. Our aim was to evaluate the effectiveness and cost-effectiveness of AI-assisted pathology for PCa diagnosis in Sweden., Methods: We modeled quadrennial prostate-specific antigen (PSA) screening for men between the ages of 50 and 74 yr over a lifetime horizon using a health care perspective. Men with PSA ≥3 ng/ml were referred for standard biopsy (SBx), for which cores were either examined via AI followed by a pathologist for AI-labeled positive cores, or a pathologist alone. The AI performance characteristics were estimated using an internal STHLM3 validation data set. Outcome measures included the number of tests, PCa incidence and mortality, overdiagnosis, quality-adjusted life years (QALYs), and the potential reduction in pathologist-evaluated biopsy cores if AI were used. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio., Key Findings and Limitations: In comparison to a pathologist alone, the AI-assisted workflow increased the number of PSA tests, SBx procedures, and PCa deaths by ≤0.03%, and slightly reduced PCa incidence and overdiagnosis. AI would reduce the proportion of biopsy cores evaluated by a pathologist by 80%. At a cost of €10 per case, the AI-assisted workflow would cost less and result in <0.001% lower QALYs in comparison to a pathologist alone. The results were sensitive to the AI cost., Conclusions and Clinical Implications: According to our model, AI-assisted pathology would significantly decrease the workload of pathologists, would not affect patient quality of life, and would yield cost savings in Sweden when compared to a human pathologist alone., Patient Summary: We compared outcomes for prostate cancer patients and relevant costs for two methods of assessing prostate biopsies in Sweden: (1) artificial intelligence (AI) technology and review of positive biopsies by a human pathologist; and (2) a human pathologist alone for all biopsies. We found that addition of AI would reduce the pathology workload and save money, and would not affect patient outcomes when compared to a human pathologist alone. The results suggest that adding AI to prostate pathology in Sweden would save costs., (Copyright © 2024. Published by Elsevier B.V.)

Background: Although there are guidelines and ideas on how to improve public health education, translating innovative approaches into actual training programs remains challenging. In this article, we provide an overview of some initiatives that tried to put this into action in different parts of the world, and present the Emerging Health Care Leader (EHCL), a novel training program developed in Switzerland., Policy Options and Recommendations: Looking at the experience of the EHCL, we propose policymakers and other interested stakeholders who wish to help reform public health education to support these initiatives not only through funding, but by valuing them through the integration of early career healthcare leaders in projects where their developing expertise can be practically applied., Conclusion: By openly sharing the experiences, strengths, weaknesses, and lessons learned with the EHCL program, we aim to foster a transparent debate on how novel training programs in public health can be organised., Competing Interests: The authors declare that they were involved in the training program described in the manuscript, either as instructors, organisers or participants., (Copyright © 2024 Martani, Ulyte, Menges, Reeves, Puhan and Heusser.)

Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare.

Background: Depression and anxiety have increased in prevalence since the start of the COVID-19 pandemic., Objective: To evaluate the consumption of antidepressants and anxiolytics from 2012 to 2022 and the pandemic's potential impact in France., Methods: We conducted an interrupted time series analysis of routine drug sales data (Medic'AM) from all French outpatient pharmacies from 2012 to 2022. We investigated trends in defined daily doses of antidepressants and anxiolytics sold per 1000 inhabitants (DDD/TID) and related expenditures before and after pandemic onset and in relation with stringency of pandemic mitigation measures. Analyses were performed descriptively and using segmented linear regression, autoregressive and autoregressive integrated moving average models., Findings: From 2012 to 2019, overall monthly antidepressant sales increased (+0.02 DDD/TID) while monthly anxiolytic sales decreased (-0.07 DDD/TID). With pandemic onset, there was a relevant and persisting trend increase (+0.20 DDD/TID per month) for antidepressant sales overall, with an estimated excess of 112.6 DDD/TID sold from May 2020 until December 2022. Anxiolytic sales were elevated from February 2020 throughout the pandemic but returned to expected levels by December 2022, with an estimated excess of 33.8 DDD/TID. There was no evident association between stringency and antidepressant or anxiolytic sales., Conclusions: This study showed a protracted trend increase in the consumption of antidepressants since pandemic onset, while increases in anxiolytic consumption were temporary., Clinical Implications: We provide evidence that the COVID-19 pandemic may have had long-lasting consequences on the prevalence and treatment of depression and anxiety disorders, requiring further actions by researchers and policy-makers to address this potential public mental health crisis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.

This article presents an algorithmic framework for real-time condition monitoring and state forecasting using multivariate data demonstrated on thermal imagery data of a ship's engine. The proposed method aims to improve the accuracy, efficiency, and robustness of condition monitoring and state predictions by identifying the most informative sampling locations of high-dimensional datasets and extracting the underlying dynamics of the system. The method is based on a combination of Proper Orthogonal Decomposition (POD), Optimal Sampling Location (OSL), and Dynamic Mode Decomposition (DMD), allowing the identification of key features in the system's behavior and predicting future states. Based on thermal imagery data, it is shown how thermal areas of interest can be classified via POD. By extracting the POD modes of the data, dimensions can be drastically reduced and via OSL, optimal sampling locations are found. In addition, nonlinear kernel-based Support Vector Regression (SVR) is used to build models between the optimal locations, enabling the imputation of erroneous data to improve the overall robustness. To build predictive data-driven models, DMD is applied on the subspace obtained by OSL, which leads to an intensive lower demand of computational resources, making the proposed method real-time applicable. Furthermore, an unsupervised approach for anomaly detection is proposed using OSL. The anomaly detection framework is coupled with the state prediction framework, which extends the capabilities to real-time anomaly predictions. In summary, this study proposes a robust predictive condition monitoring framework for real-time risk assessment.

Understanding the development of humoral immune responses of children and adolescents to SARS-CoV-2 is essential for designing effective public health measures. Here we examine the changes of humoral immune response in school-aged children and adolescents during the COVID-19 pandemic (June 2020 to July 2022), with a specific interest in the Omicron variant (beginning of 2022). In our study "Ciao Corona", we assess in each of the five testing rounds between 1874 and 2500 children and adolescents from 55 schools in the canton of Zurich with a particular focus on a longitudinal cohort (n=751). By July 2022, 96.9% (95% credible interval 95.3-98.1%) of children and adolescents have SARS-CoV-2 anti-spike IgG (S-IgG) antibodies. Those with hybrid immunity or vaccination have higher S-IgG titres and stronger neutralising responses against Wildtype, Delta and Omicron BA.1 variants compared to those infected but unvaccinated. S-IgG persist over 18 months in 93% of children and adolescents. During the study period one adolescent was hospitalised for less than 24 hours possibly related to an acute SARS-CoV-2 infection. These findings show that the Omicron wave and the rollout of vaccines boosted S-IgG titres and neutralising capacity. Trial registration number: NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717 ., (© 2023. The Author(s).)

Objectives: The correlate(s) of protection against SARS-CoV-2 remain incompletely defined. Additional information regarding the combinations of antibody and T cell-mediated immunity which can protect against (re)infection is needed., Methods: We conducted a population-based, longitudinal cohort study including 1044 individuals of varying SARS-CoV-2 vaccination and infection statuses. We assessed spike (S)- and nucleocapsid (N)-immunoglobulin(Ig)G and wildtype, Delta, and Omicron-neutralizing antibody (N-Ab) activity. In a subset of 328 individuals, we evaluated S, membrane (M), and N-specific T cells. Three months later, we reassessed Ab (n = 964) and T cell (n = 141) responses and evaluated factors associated with protection from (re)infection., Results: At the study start, >98% of participants were S-IgG seropositive. N-IgG and M/N-T-cell responses increased over time, indicating viral (re)exposure, despite existing S-IgG. Compared to N-IgG, M/N-T cells were a more sensitive measure of viral exposure. High N-IgG titers, Omicron-N-Ab activity, and S-specific-T-cell responses were all associated with a reduced likelihood of (re)infection over time., Conclusion: Population-level SARS-CoV-2 immunity is S-IgG-dominated, but heterogeneous. M/N-T-cell responses can distinguish previous infection from vaccination, and monitoring a combination of N-IgG, Omicron-N-Ab, and S-T-cell responses may help estimate protection against SARS-CoV-2 (re)infection., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Evidence on the impact of post COVID-19 condition (PCC) on work ability is limited but critical due to its high prevalence among working-age individuals. This study aimed to evaluate the association between PCC, work ability, and occupational changes in a population-based cohort., Methods: We used data from working-age adults included in a prospective, longitudinal cohort of a random sample of all individuals infected with SARS-CoV-2 between August 2020 and January 2021 in the Canton of Zurich, Switzerland. We evaluated current work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), and PCC-related occupational changes one year after infection., Findings: Of 672 individuals included in this study, 120 (17.9%) were categorised as having PCC (defined as presence of self-reported COVID-19 related symptoms) at 12 months. There was very strong evidence that current work ability scores were mean 0.62 (95% CI 0.30-0.95) points lower among those with PCC compared to those without in adjusted regression analyses. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (adjusted odds ratio (aOR) 0.30, 95% CI 0.20-0.46) and mental (aOR 0.40, 0.27-0.62) demands in individuals with PCC. Higher age and history of psychiatric diagnosis were associated with more substantial reductions in current work ability. 5.8% of those with PCC reported direct effects of PCC on their occupational situation, with 1.6% of those with PCC completely dropping out of the workforce., Interpretation: These findings highlight the need for providing support and interdisciplinary interventions to individuals affected by PCC to help them maintain or regain their work ability and productivity., Funding: Federal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland; Horizon Europe., Competing Interests: JF reports receiving grants from Gilead Sciences Switzerland, ViiV healthcare, and Merck, unrelated to this work. The other authors declare no conflicts of interest., (© 2023 The Author(s).)

Objective: To evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection., Design: Population based, longitudinal cohort., Setting: General population of canton of Zurich, Switzerland., Participants: 1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection., Main Outcome Measures: Trajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection., Results: 22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%))., Conclusions: Up to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials., Registrations: ISRCTN18181860, ., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/disclosure-of-interest(available on request from the corresponding author) and declare: funding for the research project by the Department of Health of the canton of Zurich, the University of Zurich Foundation and the Swiss Federal Office of Public Health; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We compared socio-demographic characteristics, health-related variables, vaccination-related beliefs and attitudes, vaccination acceptance, and personality traits of individuals who vaccinated against COVID-19 and who did not vaccinate by December 2021. Methods: This cross-sectional study used data of 10,642 adult participants from the Corona Immunitas eCohort, an age-stratified random sample of the population of several cantons in Switzerland. We used multivariable logistic regression models to explore associations of vaccination status with socio-demographic, health, and behavioral factors. Results: Non-vaccinated individuals represented 12.4% of the sample. Compared to vaccinated individuals, non-vaccinated individuals were more likely to be younger, healthier, employed, have lower income, not worried about their health, have previously tested positive for SARS-CoV-2 infection, express lower vaccination acceptance, and/or report higher conscientiousness. Among non-vaccinated individuals, 19.9% and 21.3% had low confidence in the safety and effectiveness of SARS-CoV-2 vaccine, respectively. However, 29.1% and 26.7% of individuals with concerns about vaccine effectiveness and side effects at baseline, respectively vaccinated during the study period. Conclusion: In addition to known socio-demographic and health-related factors, non-vaccination was associated with concerns regarding vaccine safety and effectiveness., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Sabatini, Kaufmann, Fadda, Tancredi, Noor, Van Der Linden, Cullati, Frank, Michel, Harju, Luedi, Frei, Ballouz, Menges, Fehr, Kohler, Kahlert, Scheu, Ortega, Chocano-Bedoya, Rodondi, Stringhini, Baysson, Lorthe, Zufferey, Suggs, Albanese, Vincentini, Bochud, D’Acremont, Nusslé, Imboden, Keidel, Witzig, Probst-Hensch and von Wyl.)

Long-term control of SARS-CoV-2 requires effective vaccination strategies. This has been challenged by public mistrust and the spread of misinformation regarding vaccine safety. Better understanding and communication of the longer-term and comparative experiences of individuals in the general population following vaccination are required. In this population-based longitudinal study, we included 575 adults, randomly selected from all individuals presenting to a Swiss reference vaccination center, for receipt of BNT162b2, mRNA1273, or JNJ-78436735. We assessed the prevalence, onset, duration, and severity of self-reported adverse effects over 12 weeks following vaccination. We additionally evaluated participants' perceptions of vaccines, trust in public health authorities and pharmaceutical companies, and compliance with public health measures. Most participants reported at least one adverse effect within 12 weeks following vaccination. Adverse effects were mostly mild or moderate, resolved within three days, and rarely resulted in anaphylaxis or hospitalizations. Female sex, younger age, higher education, and receipt of mRNA-1273 were associated with reporting adverse effects. Compared to JNJ-78436735 recipients, a higher proportion of mRNA vaccine recipients agreed that vaccination is important, and trusted public health authorities. Our findings provide real-world estimates of the prevalence of adverse effects following SARS-CoV-2 vaccination and highlight the importance of transparent communication to ensure the success of current or future vaccination campaigns., (© 2023. The Author(s).)

Background: Patient preferences for treatment outcomes are important to guide decision-making in clinical practice, but little is known about the preferences of patients with metastatic hormone-sensitive prostate cancer (mHSPC)., Objective: To evaluate patient preferences regarding the attributed benefits and harms of systemic treatments for mHSPC and preference heterogeneity between individuals and specific subgroups., Design Setting and Participants: We conducted an online discrete choice experiment (DCE) preference survey among 77 patients with metastatic prostate cancer (mPC) and 311 men from the general population in Switzerland between November 2021 and August 2022., Outcome Measurements and Statistical Analysis: We evaluated preferences and preference heterogeneity related to survival benefits and treatment-related adverse effects using mixed multinomial logit models and estimated the maximum survival time participants were willing to trade to avert specific adverse effects. We further assessed characteristics associated with different preference patterns via subgroup and latent class analyses., Results and Limitations: Patients with mPC showed an overall stronger preference for survival benefits in comparison to men from the general population ( p  = 0.004), with substantial preference heterogeneity between individuals within the two samples (both p  < 0.001). There was no evidence of differences in preferences for men aged 45-65 yr versus ≥65 yr, patients with mPC in different disease stages or with different adverse effect experiences, or general population participants with and without experiences with cancer. Latent class analyses suggested the presence of two groups strongly preferring either survival or the absence of adverse effects, with no specific characteristic clearly associated with belonging to either group. Potential biases due to participant selection, cognitive burden, and hypothetical choice scenarios may limit the study results., Conclusions: Given the relevant heterogeneity in participant preferences regarding the benefits and harms of treatment for mHSPC, patient preferences should be explicitly discussed during decision-making in clinical practice and reflected in clinical practice guidelines and regulatory assessment regarding treatment for mHSPC., Patient Summary: We examined the preferences (values and perceptions) of patients and men from the general population regarding the benefits and harms of treatment for metastatic prostate cancer. There were large differences between men in how they balanced the expected survival benefits and potential adverse effects. While some men strongly valued survival, others more strongly valued the absence of adverse effects. Therefore, it is important to discuss patient preferences in clinical practice., (© 2023 The Author(s).)

Background: Post COVID-19 condition (PCC) is an important complication of SARS-CoV-2 infection, affecting millions worldwide. This study aimed to evaluate the prevalence and severity of post COVID-19 condition (PCC) with novel SARS-CoV-2 variants and after prior vaccination., Methods: We used pooled data from 1350 SARS-CoV-2-infected individuals from two representative population-based cohorts in Switzerland, diagnosed between Aug 5, 2020, and Feb 25, 2022. We descriptively analysed the prevalence and severity of PCC, defined as the presence and frequency of PCC-related symptoms six months after infection, among vaccinated and non-vaccinated individuals infected with Wildtype, Delta, and Omicron SARS-CoV-2. We used multivariable logistic regression models to assess the association and estimate the risk reduction of PCC after infection with newer variants and prior vaccination. We further assessed associations with the severity of PCC using multinomial logistic regression. To identify groups of individuals with similar symptom patterns and evaluate differences in the presentation of PCC across variants, we performed exploratory hierarchical cluster analyses., Results: We found strong evidence that vaccinated individuals infected with Omicron had reduced odds of developing PCC compared to non-vaccinated Wildtype-infected individuals (odds ratio 0.42, 95% confidence interval 0.24-0.68). The odds among non-vaccinated individuals were similar after infection with Delta or Omicron compared to Wildtype SARS-CoV-2. We found no differences in PCC prevalence with respect to the number of received vaccine doses or timing of last vaccination. The prevalence of PCC-related symptoms among vaccinated, Omicron-infected individuals was lower across severity levels. In cluster analyses, we identified four clusters of diverse systemic, neurocognitive, cardiorespiratory, and musculoskeletal symptoms, with similar patterns across variants., Conclusion: The risk of PCC appears to be lowered with infection by the Omicron variant and after prior vaccination. This evidence is crucial to guide future public health measures and vaccination strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ballouz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae., Competing Interests: TPJK is a member of the board of directors of Fluidic Analytics. AA is a member of the board of directors of Mabylon AG which has funded antibody-related work in the Aguzzi lab in the past. All other authors declare no competing interests., (© 2023 The Authors.)

Context: 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., Objective: To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments., Evidence Acquisition: 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., Evidence Synthesis: 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., Conclusions: 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., Patient Summary: 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., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Digital proximity-tracing apps have been deployed in multiple countries to assist with SARS-CoV-2 pandemic mitigation efforts. However, it is unclear how their performance and effectiveness were affected by changing pandemic contexts and new viral variants of concern., Objective: The aim of this study is to bridge these knowledge gaps through a countrywide digital proximity-tracing app effectiveness assessment, as guided by the World Health Organization/European Center for Prevention and Disease Control (WHO/ECDC) indicator framework to evaluate the public health effectiveness of digital proximity-tracing solutions., Methods: We performed a descriptive analysis of the digital proximity-tracing app SwissCovid in Switzerland for 3 different periods where different SARS-CoV-2 variants of concern (ie, Alpha, Delta, and Omicron, respectively) were most prevalent. In our study, we refer to the indicator framework for the evaluation of public health effectiveness of digital proximity-tracing apps of the WHO/ECDC. We applied this framework to compare the performance and effectiveness indicators of the SwissCovid app., Results: Average daily registered SARS-CoV-2 case rates during our assessment period from January 25, 2021, to March 19, 2022, were 20 (Alpha), 54 (Delta), and 350 (Omicron) per 100,000 inhabitants. The percentages of overall entered authentication codes from positive tests into the SwissCovid app were 9.9% (20,273/204,741), 3.9% (14,372/365,846), and 4.6% (72,324/1,581,506) during the Alpha, Delta, and Omicron variant phases, respectively. Following receipt of an exposure notification from the SwissCovid app, 58% (37/64, Alpha), 44% (7/16, Delta), and 73% (27/37, Omicron) of app users sought testing or performed self-tests. Test positivity among these exposure-notified individuals was 19% (7/37) in the Alpha variant phase, 29% (2/7) in the Delta variant phase, and 41% (11/27) in the Omicron variant phase compared to 6.1% (228,103/3,755,205), 12% (413,685/3,443,364), and 41.7% (1,784,951/4,285,549) in the general population, respectively. In addition, 31% (20/64, Alpha), 19% (3/16, Delta), and 30% (11/37, Omicron) of exposure-notified app users reported receiving mandatory quarantine orders by manual contact tracing or through a recommendation by a health care professional., Conclusions: In constantly evolving pandemic contexts, the effectiveness of digital proximity-tracing apps in contributing to mitigating pandemic spread should be reviewed regularly and adapted based on changing requirements. The WHO/ECDC framework allowed us to assess relevant domains of digital proximity tracing in a holistic and systematic approach. Although the Swisscovid app mostly worked, as reasonably expected, our analysis revealed room for optimizations and further performance improvements. Future implementation of digital proximity-tracing apps should place more emphasis on social, psychological, and organizational aspects to reduce bottlenecks and facilitate their use in pandemic contexts., (©Paola Daniore, Vasileios Nittas, Tala Ballouz, Dominik Menges, André Moser, Marc Höglinger, Petra Villiger, Krisztina Schmitz-Grosz, Viktor Von Wyl. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 11.11.2022.)

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., Competing Interests: The authors have declared that no competing interests exist.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID)., Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration., Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022., Exposures: Symptomatic SARS-CoV-2 infection., Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age., Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months., Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection., (© 2022. The Author(s).)

Background: Digital proximity tracing (DPT) aims to complement manual contact tracing (MCT) in identifying exposed contacts and preventing further transmission of SARS-CoV-2 in the population. Although several DPT apps, including SwissCovid, have shown to have promising effects on mitigating the pandemic, several challenges have impeded them from fully achieving the desired results. A key question now relates to how the effectiveness of DPT can be improved, which requires a better understanding of factors influencing its processes., Objective: In this study, we aim to provide a detailed examination of the exposure notification (EN) cascade and to evaluate potential contextual influences for successful receipt of an EN and subsequent actions taken by cases and contacts in different exposure settings., Methods: We used data from 285 pairs of SARS-CoV-2-infected cases and their contacts within an observational cohort study of cases and contacts identified by MCT and enrolled between August 6, 2020, and January 17, 2021, in the canton of Zurich, Switzerland. We surveyed participants with electronic questionnaires. Data were summarized descriptively and stratified by exposure setting., Results: We found that only 79 (58.5%) of 135 contacts using the SwissCovid app whose corresponding cases reported to have triggered the EN also received one. Of these, 18 (22.8%) received the EN before MCT. Compared to those receiving an EN after MCT (61/79, 77.2%), we observed that a higher proportion of contacts receiving an EN before MCT were exposed in nonhousehold settings (11/18, 61.1%, vs 34/61, 55.7%) and their corresponding cases had more frequently reported mild-to-moderate symptoms (14/18, 77.8%, vs 42/61, 68.9%). Of the 18 contacts receiving an EN before MCT, 14 (77.8%) took recommended measures: 12 (66.7%) were tested for SARS-CoV-2, and 7 (38.9%) called the SwissCovid Infoline. In nonhousehold settings, the proportion of contacts taking preventive actions after receiving an EN was higher compared to same-household settings (82%, vs 67%). In addition, 1 (9%) of 11 ENs received in the nonhousehold setting before MCT led to the identification of a SARS-CoV-2-infected case by prompting the contact to get tested. This corresponds to 1 in 85 exposures of a contact to a case in a nonhousehold setting, in which both were app users and the case triggered the EN., Conclusions: Our descriptive evaluation of the DPT notification cascade provides further evidence that DPT is an important complementary tool in pandemic mitigation, especially in nonhousehold exposure settings. However, the effect of DPT apps can only be exerted if code generation processes are efficient and exposed contacts are willing to undertake preventive actions. This highlights the need to focus efforts on keeping barriers to efficient code generation as low as possible and promoting not only app adoption but also compliance with the recommended measures upon an EN., Trial Registration: International Standard Randomised Controlled Trial Number Registry 14990068; https://doi.org/10.1186/ISRCTN14990068., (©Tala Ballouz, Dominik Menges, Hélène E Aschmann, Ruedi Jung, Anja Domenghino, Jan S Fehr, Milo A Puhan, Viktor von Wyl. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 19.05.2022.)

Background: Isolation is an indispensable measure to contain the SARS-CoV-2 virus, but it may have a negative impact on mental health and overall wellbeing. Evidence on the isolation experience, facilitating and complicating factors is needed to mitigate negative effects., Methods and Findings: This observational, population-based cohort study enrolled 1547 adults from the general population with SARS-CoV-2 infection reported to authorities between 27 February 2020 and 19 January 2021 in Zurich, Switzerland. We assessed the proportion of individuals reporting symptoms of depression and anxiety before, during and after isolation (by DASS-21), and queried worries, positive experiences, and difficulties. We analyzed the association of these outcomes with socio-demographics using ordinal regression. Additionally, we report free-text statements by participants to capture most important aspects of isolation. The proportion of participants affected by depression or anxiety increased during isolation from 10·0% to 17·1% and 9·1% to 17·6%, respectively. Ordinal regression showed that taking care of children increased the difficulty of isolation (OR 2·10, CI 1·43-3·08) and risk of non-compliance (OR 1·63, CI 1·05-2·53), especially in younger participants. A facilitating factor that individuals commonly expressed was receiving more support during isolation., Conclusion: Isolation due to SARS-CoV-2 presents a mental burden, especially for younger individuals and those taking care of children. Public health authorities need to train personnel and draw from community-based resources to provide targeted support, information, and guidance to individuals during isolation. Such efforts could alleviate the negative impact isolation has on the mental and physical health of individuals and ensure compliance of the population with recommendations., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To synthesize existing evidence on prevalence as well as clinical and socio-economic aspects of Long COVID. Methods: An umbrella review of reviews and a targeted evidence synthesis of their primary studies, including searches in four electronic databases, reference lists of included reviews, as well as related article lists of relevant publications. Results: Synthesis included 23 reviews and 102 primary studies. Prevalence estimates ranged from 7.5% to 41% in non-hospitalized adults, 2.3%-53% in mixed adult samples, 37.6% in hospitalized adults, and 2%-3.5% in primarily non-hospitalized children. Preliminary evidence suggests that female sex, age, comorbidities, the severity of acute disease, and obesity are associated with Long COVID. Almost 50% of primary studies reported some degree of Long COVID-related social and family-life impairment, long absence periods off work, adjusted workloads, and loss of employment. Conclusion: Long COVID will likely have a substantial public health impact. Current evidence is still heterogeneous and incomplete. To fully understand Long COVID, well-designed prospective studies with representative samples will be essential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nittas, Gao, West, Ballouz, Menges, Wulf Hanson and Puhan.)

Background: Patients in intensive care units (ICUs) are at high risk of developing physical, functional, cognitive, and mental impairments. Early mobilisation aims to improve patient outcomes and is increasingly considered the standard of care. This survey aimed to investigate the characteristics, current use and variations of early mobilisation and rehabilitation in Swiss ICUs., Methods: We conducted a cross-sectional survey among all ICU lead physicians, who provided data on their institutional characteristics, early mobilisation and rehabilitation practices, and their perceptions of the use and variation of early rehabilitation practices in Switzerland., Results: The survey response rate was 44% (37/84). Among ICUs caring for adults (34/37), 26 were in the German-speaking region, five in the French-speaking region, and three in the Italian-speaking region. All ICUs regularly involved physiotherapy in the rehabilitation process and 50% reported having a specialised physiotherapy team. All ICUs reported performing early mobilisation, starting within the first 7 days after ICU admission. About half reported the use of a rehabilitation (45%) or early mobilisation protocol (50%). Regular, structured, interdisciplinary rounds or meetings of the ICU care team to discuss rehabilitation measures and goals for patients were stated to be held by 53%. The respondents stated that 82% of their patients received early mobilisation measures during their ICU stay. Most frequently provided mobilisation measures included passive range of motion (97%), passive chair position in bed (97%), active range of motion muscle activation and training (88%), active side to side turning (91%), sitting on the edge of the bed (94%), transfer from bed to a chair (97%), and ambulation (94%). The proportion of ICUs providing a specific early mobilisation measure, the proportion of patients receiving it, and the time dedicated to it varied across language regions, hospital types, ICU types, and ICU sizes. Almost one third of the ICU lead physicians considered early rehabilitation to be underused in their own ICU and about half considered it to be underused in Switzerland more generally. ICU lead physicians stressed lack of personnel, financial resources, and time as key causes for underuse. Moreover, they highlighted the importance of early and systematic or protocol-based rehabilitation and interprofessional approaches that are adaptive to the patients' rehabilitation needs and potential., Conclusion: This survey suggests that almost all ICUs in Switzerland practice some form of early mobilisation with the aim of early rehabilitation. However, the described approaches, as well as the reported use of early mobilisation measures were heterogenous across Swiss ICUs.

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS., (© 2022. The Author(s).)

Background: Since the benefit-harm balance of adding inhaled corticosteroids to long-acting β 2 -agonists (LABA) and long-acting muscarinic antagonists (LAMA) for patients with chronic obstructive pulmonary disease is unclear, we evaluated this addition for a range of patient profiles., Methods: Analyses considered the effects of low-to-moderate doses of inhaled corticosteroids, LABA, and LAMA compared with LABA and LAMA alone, outcome incidences, and preference weights assigned to averted moderate-to-severe exacerbations (benefit) and severe pneumonia, candidiasis, and dysphonia (harm). Using exponential models, we estimated the preference weight-adjusted 2-year net clinical benefit (ie, benefits outweighing harms) indices. Exacerbation risk thresholds for triggering inhaled corticosteroids, LABA, and LAMA were established when the probability of a 2-year net clinical benefit reached 60%. We estimated the proportion of patients benefiting from added inhaled corticosteroids using an externally validated prediction model for acute exacerbations in primary care., Findings: Adding low-to-moderate dose inhaled corticosteroids to LABA and LAMA provided a net clinical benefit in patients with a 2-year baseline exacerbation risk of 54-83%. Low-dose inhaled corticosteroids showed a net clinical benefit if the baseline risk was 40-91%, but not at higher doses. The benefit was modified by blood eosinophil count (BEC) and age. Although no net benefit was associated with a BEC of less than 150 cells per μL, patients with a BEC of 150 cells per μL or more had a net benefit from low-dose inhaled corticosteroids with a 2-year exacerbation risk of 32-95% in those aged 40-79 years and 41-93% in those older than 80 years. A moderate dose of inhaled corticosteroids showed a net benefit in patients younger than 80 years with a BEC of 150 cells per μL or more at 52-86% 2-year exacerbation risk. Depending on the subgroups, the proportion of patients with a net benefit from added inhaled corticosteroids ranged from 0 to 68%., Interpretation: The net clinical benefit of adding different inhaled corticosteroid doses to LABA and LAMA varies greatly with exacerbation risk, BEC, and age. Personalised treatment decisions based on these factors and predicted exacerbation risks might reduce overtreatment and undertreatment with inhaled corticosteroids., Funding: None., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)