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ImportanceSome individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).ObjectiveTo 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 ParticipantsBayesian 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.ExposuresSymptomatic SARS-CoV-2 infection.Main Outcomes and MeasuresProportion 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.ResultsA 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 RelevanceThis 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.

In longitudinal studies with time-varying exposures and mediators, the mediational g-formula is an important method for the assessment of direct and indirect effects. However, current methodologies based on the mediational g-formula can deal with only one mediator. This limitation makes these methodologies inapplicable to many scenarios. Hence, we develop a novel methodology by extending the mediational g-formula to cover cases with multiple time-varying mediators. We formulate two variants of our approach that are each suited to a distinct set of assumptions and effect definitions and present nonparametric identification results of each variant. We further show how complex causal mechanisms (whose complexity derives from the presence of multiple time-varying mediators) can be untangled. We implemented a parametric method, along with a user-friendly algorithm, in R software. We illustrate our method by investigating the complex causal mechanism underlying the progression of chronic obstructive pulmonary disease. We found that the effects of lung function impairment mediated by dyspnea symptoms accounted for 14.6% of the total effect and that mediated by physical activity accounted for 11.9%. Our analyses thus illustrate the power of this approach, providing evidence for the mediating role of dyspnea and physical activity on the causal pathway from lung function impairment to health status. See video abstract at, http://links.lww.com/EDE/B988 .

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis. However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

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

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.

Purpose To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19. Methods Prospective observational cohort study of adults (age ≥18 years) with confirmed or highly suspected COVID-19 recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland and Wales. Patients were recruited between 27 August 2020 and 17 February 2021, with at least 4 weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups. Results 76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77 to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI 0.75 to 0.77)) demonstrated consistent discrimination across all nine National Health Service regions, with similar performance metrics to the original validation cohorts. Calibration remained stable (4C Mortality: pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C Deterioration: 1.00, –0.04), with no need for temporal recalibration during the second UK pandemic wave of hospital admissions. Conclusion Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective second wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with COVID-19, both scores can continue to inform clinical decision making. Trial registration number ISRCTN66726260.

Background: We aimed to determine whether living in a household with children is associated with SARS-CoV-2 seropositivity in adults and investigated interacting factors that may influence this association. Methods: SARS-CoV-2 serology testing was performed in randomly selected individuals from the general population between end of October 2020 and February 2021 in 11 cantons in Switzerland. Data on sociodemographic and household characteristics, employment status, and health-related history was collected using questionnaires. Multivariable logistic regression was used to examine the association of living with children, + ID der Publikation: unilu_59486 + Sprache: Englisch + Letzte Aktualisierung: 2022-06-27 14:52:01

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program. FRAMEWORK: An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program. SCREENING APPROACH: General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a “lung health check”. Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules. CONCLUSION: Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make.

Background Common mental disorders (CMDs) are highly prevalent and contribute significantly to the global burden of disease, yet there is evidence of a large treatment gap. We aimed to quantify this gap among young adults with symptoms of CMDs and examine the relationship between substance use and perceived need for care and mental health service utilization. Methods In a nationally representative, cross-sectional survey of young Swiss adults’ mental health and wellbeing, we assessed symptoms of anxiety, depression, and attention deficit hyperactivity disorder (ADHD) with widely used screening instruments and asked about participant suicidal ideation, suicide attempts, mental health-related quality of life, alcohol and drug use, perceived need for mental health care, and mental health service utilization. We used these variables to calculate the treatment gap and weighted all analyses according to the stratified sampling plan. Results Around a quarter of young adults screened positive for at least one CMD. Participants who screened positive for anxiety and/or depression reported significantly more suicidal ideation and lifetime suicide attempts and reported worse mental health-related quality of life than participants who did not screen positive for a disorder. Women’s prevalence of anxiety and depression symptoms was significantly higher than men’s, while men were more likely to report most types of risky drug use. Among those with a CMD, only around half perceived lifetime need for care, and less than 20% reported currently utilizing mental health services. Young adults with a CMD reporting risky weekly use of alcohol were less likely to be currently using services. Conclusion The high prevalence of CMD symptoms could reflect a rising prevalence of these disorders mirroring increasing trends observed in other countries. To address the large treatment gap, interventions promoting mental health literacy and more research on additional barriers to inform further interventions are needed.

Background: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. Methods/design: The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson's Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. Discussion: The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. Trial registration: ISRCTN12051706. This work was supported by the Mobilise-D project that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 820820. This JU receives support from the European Union's Horizon 2020 research and innovation program and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The funding bodies do not have ultimate authority over any activities (study design, collection, management, analysis, interpretation of data, writing of reports and decision to submit for publication. A draft protocol for the clinical validation was provided as part of the grant/funding application. Content in this publication reflects the authors’ view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein. ISGlobal acknowledges support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Heleen Demeyer is a post-doctoral fellow of the FWO Flanders. Heiko Gaßner is supported by the Fraunhofer Internal Programs under Grant No. Attract 044-602140 and 044-602150

Background At present, effectively implementing smoking cessation programs in the health care system constitutes a major challenge. A unique opportunity to initiate smoking cessation focuses on smokers scheduled for surgery. These patients are not only highly motivated to quit smoking but also likely to benefit from a reduction in postoperative complications which may translate into a decrease of costs. Nevertheless, surgical patients are not routinely informed about the benefits of preoperative smoking cessation. Potential reasons for this missed opportunity may be the lack of time and training of surgeons and anaesthesiologists. We therefore aim to analyse the impact of a preoperative high-intensity smoking cessation intervention on surgical complications up to a 90-day postoperative period in patients of various surgical disciplines. The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing intermediate to high-risk surgery. Methods The present study is a single-centre, randomized trial with two parallel groups of smokers scheduled for surgery comparing surgery alone and surgery with preoperative smoking cessation. We plan to randomize 251 patients. The primary objective is to compare complications between patients with an institutional multifaceted smoking cessation intervention starting 4 weeks before surgery compared to patients in the advice-only group (control group) within a 90-day postoperative period. The primary endpoint is the Comprehensive Complication Index (CCI®) within 90 days of surgery. Secondary outcomes include the length of hospital stay, cost of care, quality of life, smoking abstinence, and reduction in nicotine consumption. Discussion The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing surgery. Trial registration BASEC #2021-02004; ClinicalTrials.gov: NCT05192837. Registered on January 14, 2022.

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

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.

Summary One-stage meta-analysis of individual participant data (IPD) poses several statistical and computational challenges. For time-to-event outcomes, the approach requires the estimation of complicated nonlinear mixed-effects models that are flexible enough to realistically capture the most important characteristics of the IPD. We present a model class that incorporates general normally distributed random effects into linear transformation models. We discuss extensions to model between-study heterogeneity in baseline risks and covariate effects and also relax the assumption of proportional hazards. Within the proposed framework, data with arbitrary random censoring patterns can be handled. The accompanying $\textsf{R}$ package tramME utilizes the Laplace approximation and automatic differentiation to perform efficient maximum likelihood estimation and inference in mixed-effects transformation models. We compare several variants of our model to predict the survival of patients with chronic obstructive pulmonary disease using a large data set of prognostic studies. Finally, a simulation study is presented that verifies the correctness of the implementation and highlights its efficiency compared to an alternative approach.

BACKGROUND: Mask 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. This study explored perceptions of the usefulness of masks in school and public in a cohort of children and adolescents in the canton of Zurich, Switzerland, in January to May 2021. METHODS: School children aged 10 to 17 years enrolled in Ciao Corona, a prospective school-based cohort study, responded to nested online surveys between 12 January and 24 March 2021 (Q1) and 10 March and 16 May 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 the children’s perception of the usefulness of masks and mask wearing behaviour by applying a non-validated questionnaire. Associations between perceived usefulness of masks and child’s school level and gender, and parents’ educational attainment were analysed with Pearson’s and McNemar’s chi-square tests. Free-text comments provided by children were classified into categories of expressed attitude towards mask wearing. RESULTS: A total of 595 (54% girls) and 1118 (52% girls) school children with predominantly Swiss nationality and a high socioeconomic status responded to online questionnaires at Q1 and Q2, respectively. More than half of the 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%). 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. CONCLUSIONS: Approximately 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. A validation of the questionnaire is needed.

Background The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence. Methods We included 5947 children diagnosed with cancer in Switzerland during 1985–2015 at 0–15 years of age from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardisation to adjust for age and year of diagnosis. We examined whether the spatial variation of risk can be explained by modelled ambient air concentration of NO2, modelled exposure to background ionising radiation, area-based socio-economic position (SEP), linguistic region, duration in years of general cancer registration in the canton or degree of urbanisation. Results For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for central nervous system (CNS) tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was weak evidence of an association of CNS tumour incidence with modelled exposure to background ionising radiation (RR per SD difference 1.17; 0.98–1.40) and with SEP (1.6; 1.00–1.13). Conclusion Of the investigated diagnostic groups, childhood CNS tumours showed the largest spatial variation. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role.

BACKGROUND AND AIMS: Among people on opioid agonist treatment (OAT), social-environmental and behavioural risk factors may promote the spread of SARS-CoV-2, and somatic comorbidities are highly prevalent. Thus, this population is considered at elevated risk for being infected as well as for developing a more severe course of COVID-19 disease. The aim was to assess the SARS-CoV-2 seroprevalence among people in ongoing OAT, to explore whether the antibody positive group differed from the antibody negative group, and to compare the SARS-CoV-2 seroprevalence among OAT patients with the prevalence in the regional general population. METHODS: The nationwide Corona Immunitas study assessed the participants’ Sars-CoV-2 antibody status, social characteristics and behavioural data after the first wave of the corona pandemic in Switzerland, between the end of June and beginning of September 2020. We analysed the subsample of OAT patients (n = 122) and the subsample from the general population of the canton of Zurich (n = 472). RESULTS: SARS-CoV-2 seroprevalence in the general population (mean age ± standard deviation 44.7 ± 11.7 years; 50.9% female) was 3.5% (95% confidence interval [CI] 2.2–4.8%) vs 9.8% (5.1–17.2%) in the OAT population age 44.3 ± 9.4 years; 30.3% female), corresponding to a prevalence ratio of 2.9 (95% CI 1.37–5.94; p = 0.004). OAT patients had a significantly worse health status than the general population. In the OAT group, we found no significant difference between seropositive and seronegative individuals regarding socioeconomic status, risk behaviour, COVID-19-related symptoms or comorbidity. None of the OAT patients who tested positive had a severe course of COVID-19. CONCLUSION: The 3-fold higher seroprevalence suggests a higher than average viral exposure in the OAT group. Nevertheless, no severe COVID-19 course occurred, although the number of study participants was relatively small. One possible reason for this could be possible cross-immunity to SARS-CoV-2 due to frequent viral contacts in OAT patients. ISRCTN Registry: http://www.isrctn.com/ISRCTN18181860

The new ERS statement facilitates standardisation of conducting, reporting and interpreting cardiopulmonary exercise tests in chronic lung diseases. The conclusions are especially valuable for multicentre comparisons and for establishing global reference data.http://bit.ly/32Y0eO0

Alternative nicotine products such as electronic nicotine delivery systems (ENDS) and tobacco heating systems have gained worldwide popularity. Findings suggest ENDS to be probably less harmful than combustible cigarettes, but evidence on long-term health effects is still lacking. The potential risk reduction by using tobacco heating systems instead of combustible cigarettes has largely been studied by tobacco industry-sponsored research. Evidence on the extent of risk reduction is key for risk-adapted taxation policies, which will be discussed soon in the Swiss parliament. Evidence on the effects of tax policies in the USA shows that the level of taxation of ENDS, tobacco heating systems and combustible cigarettes has an effect on switches between these products. Therefore, excise taxes influencing one another need to be considered. In Switzerland, tobacco heating systems are currently taxed at a level of 12%, whereas ENDS are not subject to tobacco excise taxation as yet, because they do not meet the legal definition of a tobacco product. This article analyses approaches for imposing taxes on tobacco and nicotine products and possible outcomes, depending on the intended public health goals. At least three tax models can be considered. Tax model A would apply a very small tax on ENDS and a higher tax for tobacco products, which could increase incentives for smokers to switch to vaping but comes with risks of increased vaping initiation among the youth and subsequent switch to or dual use of tobacco products. In contrast, model B would levy a moderate tax on ENDS and an increased tax on tobacco products, which could limit initiation among youth, incentivise to switch from smoking to vaping and discourage dual use. In model C, a comparable tax level for ENDS, tobacco heating systems and combustible cigarettes is levied. This could have overall positive effects in reducing tobacco- and nicotine-associated burden of disease by discouraging initiation in youth, overall consumption and dual use, but could discourage switching to less harmful products. When applying these tax models to current sales prices of these products we found that no public health goal, such as protecting youth and reducing tobacco-associated morbidity and mortality can be achieved. The price of tobacco products is too low to achieve any price differentiation that reflects the different risks associated with ENDS and tobacco products. In order to achieve any public health goal with one of these tax models, prices for tobacco products need to be increased substantially.

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide novel insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function. Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations. Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD., Editorial summary Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.

Background Digital proximity tracing apps have been released to mitigate the transmission of SARS-CoV-2, the virus known to cause COVID-19. However, it remains unclear how the acceptance and uptake of these apps can be improved. Objective This study aimed to investigate the coverage of the SwissCovid app and the reasons for its nonuse in Switzerland during a period of increasing incidence of COVID-19 cases. Methods We collected data between September 28 and October 8, 2020, via a nationwide online panel survey (COVID-19 Social Monitor, N=1511). We examined sociodemographic and behavioral factors associated with app use by using multivariable logistic regression, whereas reasons for app nonuse were analyzed descriptively. Results Overall, 46.5% (703/1511) of the survey participants reported they used the SwissCovid app, which was an increase from 43.9% (662/1508) reported in the previous study wave conducted in July 2020. A higher monthly household income (ie, income >CHF 10,000 or >US $11,000 vs income ≤CHF 6000 or Conclusions Eliminating technical hurdles and communicating the benefits of digital proximity tracing apps are crucial to promote further uptake and adherence of such apps and, ultimately, enhance their effectiveness to aid pandemic mitigation strategies.

Background The availability and use of health apps continues to increase, revolutionizing the way mobile health interventions are delivered. Apps are increasingly used to prevent disease, improve well-being, and promote healthy behavior. On a similar rise is the incidence of skin cancers. Much of the underlying risk can be prevented through behavior change and adequate sun protection. Self-monitoring apps have the potential to facilitate prevention by measuring risk (eg, sun intensity) and encouraging protective behavior (eg, seeking shade). Objective Our aim was to assess health care consumer preferences for sun protection with a self-monitoring app that tracks the duration and intensity of sun exposure and provides feedback on when and how to protect the skin. Methods We conducted an unlabeled discrete choice experiment with 8 unique choice tasks, in which participants chose among 2 app alternatives, consisting of 5 preidentified 2-level attributes (self-monitoring method, privacy control, data sharing with health care provides, reminder customizability, and costs) that were the result of a multistep and multistakeholder qualitative approach. Participant preferences, and thus, the relative importance of attributes and their levels were estimated using conditional logit modeling. Analyses consisted of 200 usable surveys, yielding 3196 observations. Results Our respondents strongly preferred automatic over manually operated self-monitoring (odds ratio [OR] 2.37, 95% CI 2.06-2.72) and no cost over a single payment of 3 Swiss francs (OR 1.72, 95% CI 1.49-1.99). They also preferred having over not having the option of sharing their data with a health care provider of their choice (OR 1.66, 95% CI 1.40-1.97), repeated over single user consents, whenever app data are shared with commercial thirds (OR 1.57, 95% CI 1.31-1.88), and customizable over noncustomizable reminders (OR 1.30, 95% CI 1.09-1.54). While most participants favored thorough privacy infrastructures, the attribute of privacy control was a relatively weak driver of app choice. The attribute of self-monitoring method significantly interacted with gender and perceived personal usefulness of health apps, suggesting that female gender and lower perceived usefulness are associated with relatively weaker preferences for automatic self-monitoring. Conclusions Based on the preferences of our respondents, we found that the utility of a self-monitoring sun protection app can be increased if the app is simple and adjustable; requires minimal effort, time, or expense; and has an interoperable design and thorough privacy infrastructure. Similar features might be desirable for preventive health apps in other areas, paving the way for future discrete choice experiments. Nonetheless, to fully understand these preference dynamics, further qualitative or mixed method research on mobile self-monitoring-based sun protection and broader preventive mobile self-monitoring is required. International Registered Report Identifier (IRRID) RR2-10.2196/16087

Outcomes of very preterm infants vary considerably between health care facilities. Our objective was to compare outcome and practices between the Swiss Neonatal Network (SNN) and US members of the Vermont Oxford Network (US-VON).Retrospective observational study including all live-born infants with a birth weight between 501 and 1500 g as registered by SNN and US-VON between 2012 and 2014. We performed multivariable and propensity score-matched analyses of neonatal outcome by adjusting for case-mix, race, prenatal care, and unit-level factors, and compared indirectly standardized practices.A total of 123 689 infants were born alive in 696 US-VON units and 2209 infants were born alive in 13 SNN units. Adjusted risk ratios (aRRs) for the composite "death or major morbidity" (aRR: 0.56, 95% confidence interval: 0.51-0.62) and all other outcomes were either comparable or lower in SNN except for mortality, for which aRR was higher (aRR: 1.28, 95% confidence interval: 1.09-1.50). Propensity score matching and restricting the analysis to infants for which we expect no survival bias, because both networks routinely initiate intensive care at birth, revealed comparable aRR. Variations in observed practices between SNN and US-VON were large.The SNN units had a significantly lower risk ratio for death or major morbidity. Despite higher mortality, this difference is independent of survival bias. The higher delivery room mortality reflects the SNN practice to favor primary nonintervention for infants born24 completed gestational weeks. We propose further research into which practice differences have the strongest beneficial impact.

The vicious circle of dyspnoea–inactivity has been proposed, but never validated empirically, to explain the clinical course of chronic obstructive pulmonary disease (COPD). We aimed to develop and validate externally a comprehensive vicious circle model.We utilised two methods. 1) Identification and validation of all published vicious circle models by a systematic literature search and fitting structural equation models to longitudinal data from the Spanish PAC-COPD (Phenotype and Course of COPD) cohort (n=210, mean age 68 years, mean forced expiratory volume in 1 s (FEV1) 54% predicted), testing both the hypothesised relationships between variables in the model (“paths”) and model fit. 2) Development of a new model and external validation using longitudinal data from the Swiss and Dutch ICE COLD ERIC (International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts) cohort (n=226, mean age 66 years, mean FEV157% predicted).We identified nine vicious circle models for which structural equation models confirmed most hypothesised paths but showed inappropriate fit. In the new model, airflow limitation, hyperinflation, dyspnoea, physical activity, exercise capacity and COPD exacerbations remained related to other variables and model fit was appropriate. Fitting it to ICE COLD ERIC, all paths were replicated and model fit was appropriate.Previously published vicious circle models do not fully explain the vicious circle concept. We developed and externally validated a new comprehensive model that gives a more relevant role to exercise capacity and COPD exacerbations.

Background Digital innovations continue to shape health and health care. As technology socially integrates into daily living, the lives of health care consumers are transformed into a key source of health information, commonly referred to as patient-generated health data (PGHD). With chronic disease prevalence signaling the need for a refocus on primary prevention, electronic PGHD might be essential in strengthening proactive and person-centered health care. Objective This study aimed to review and synthesize the existing literature on the utilization and implications of electronic PGHD for primary disease prevention and health promotion purposes. Methods Guided by a well-accepted methodological framework for scoping studies, we screened MEDLINE, CINAHL, PsycINFO, Scopus, Web of Science, EMBASE, and IEEE Digital Library. We hand-searched 5 electronic journals and 4 gray literature sources, additionally conducted Web searches, reviewed relevant Web pages, manually screened reference lists, and consulted authors. Screening was based on predefined eligibility criteria. Data extraction and synthesis were guided by an adapted PGHD-flow framework. Beyond initial quantitative synthesis, we reported narratively, following an iterative thematic approach. Raw data were coded, thematically clustered, and mapped, allowing for the identification of patterns. Results Of 183 eligible studies, targeting knowledge and self-awareness, behavior change, healthy environments, and remote monitoring, most literature (125/183, 68.3%) addressed weight reduction, either through physical activity or nutrition, applying a range of electronic tools from socially integrated to full medical devices. Participants generated their data actively (100/183, 54.6%), in combination with passive sensor-based trackers (63/183, 34.4%) or entirely passively (20/183, 10.9%). The proportions of active and passive data generation varied strongly across prevention areas. Most studies (172/183, 93.9%) combined electronic PGHD with reflective, process guiding, motivational and educational elements, highlighting the role of PGHD in multicomponent digital prevention approaches. Most of these interventions (110/183, 60.1%) were fully automatized, underlining broader trends toward low-resource and efficiency-driven care. Only a fraction (47/183, 25.6%) of studies provided indications on the impact of PGHD on prevention-relevant outcomes, suggesting overall positive trends, especially on vitals (eg, blood pressure) and body composition measures (eg, body mass index). In contrast, the impact of PGHD on health equity remained largely unexplored. Finally, our analysis identified a list of barriers and facilitators clustered around data collection and use, technical and design considerations, ethics, user characteristics, and intervention context and content, aiming to guide future PGHD research. Conclusions The large, heterogeneous volume of the PGHD literature underlines the topic’s emerging nature. Utilizing electronic PGHD to prevent diseases and promote health is a complex matter owing to mostly being integrated within automatized and multicomponent interventions. This underlines trends toward stronger digitalization and weaker provider involvement. A PGHD use that is sensitive to identified barriers, facilitators, consumer roles, and equity considerations is needed to ensure effectiveness.

Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what “physical activity” means to COPD patients and how their perspective is best measured is poorly understood. We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments). 116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III–IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised. Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity. The themes were similar irrespective of country, demographic or disease characteristics. Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period. For the first time, our approach provides comprehensive insight on physical activity from the COPD patients’ perspective. The PROactive PRO instruments’ content validity represents the pivotal basis for empirically based item reduction and validation., Conceptual framework as basis of PROactive PRO instruments to assess physical activity from COPD patient perspective http://ow.ly/ytJoS

Public health research is complex, involves various disciplines, epistemological perspectives and methods, and is rarely conducted in a controlled setting. Often, the added value of a research project lies in its inter- or trans-disciplinary interaction, reflecting the complexity of the research questions at hand. This creates specific challenges when writing and reviewing public health research grant applications. Therefore, the German Research Foundation (DFG), the largest independent research funding organization in Germany, organized a round table to discuss the process of writing, reviewing and funding public health research. The aim was to analyse the challenges of writing, reviewing and granting scientific public health projects and to improve the situation by offering guidance to applicants, reviewers and funding organizations. The DFG round table discussion brought together national and international public health researchers and representatives of funding organizations. Based on their presentations and discussions, a core group of the participants (the authors) wrote a first draft on the challenges of writing and reviewing public health research proposals and on possible solutions. Comments were discussed in the group of authors until consensus was reached. Public health research demands an epistemological openness and the integration of a broad range of specific skills and expertise. Applicants need to explicitly refer to theories as well as to methodological and ethical standards and elaborate on why certain combinations of theories and methods are required. Simultaneously, they must acknowledge and meet the practical and ethical challenges of conducting research in complex real life settings. Reviewers need to make the rationale for their judgments transparent, refer to the corresponding standards and be explicit about any limitations in their expertise towards the review boards. Grant review boards, funding organizations and research ethics committees need to be aware of the specific conditions of public health research, provide adequate guidance to applicants and reviewers, and ensure that processes and the expertise involved adequately reflect the topic under review. peerReviewed

Synthesizing evidence from comparative effectiveness trials can be difficult because multiple outcomes of different importance are to be considered. The goal of this study was to demonstrate an approach to conducting quantitative benefit-harm assessment that considers patient preferences.We conducted a benefit-harm assessment using data from the Multicenter Uveitis Steroid Treatment Trial that compared corticosteroid implant versus systemic corticosteroids and immunosuppression in non-infectious intermediate, posterior, and panuveitis. We focused on clinical outcomes considered important to patients, including visual acuity, development of cataracts/glaucoma, need for eye surgery, prescription-requiring hypertension, hyperlipidemia, and infections. Patient preferences elicited in a recent survey were then incorporated into our assessment of the benefit-harm balance.Benefit-harm metrics were calculated for each time point that summarized the numbers of outcomes, caused or prevented by implant therapy versus systemic therapy if 1000 patients were treated. The benefit-harm metric was -129 (95% confidence interval: -242 to -14), -317 (-436 to -196), -390 (-514 to -264), and -526 (-687 to -368) at 6, 12, 18, and 24 months follow up, respectively, suggesting that systemic therapy may have a better benefit-harm balance. However, measures of quality of life for patients treated with implant therapy were found to be better than patients treated with systemic therapy over the same time period.Results of benefit-harm assessment were different from the prospectively collected quality of life data during trial follow up. Future studies should explore the reasons for such discrepancies and the strength and weakness of each method to assess treatment benefits and harms.

The assessment of physical activity in healthy populations and in those with chronic diseases is challenging. The aim of this systematic review was to identify whether available activity monitors (AM) have been appropriately validated for use in assessing physical activity in these groups. Following a systematic literature search we found 134 papers meeting the inclusion criteria; 40 conducted in a field setting (validation against doubly labelled water), 86 in a laboratory setting (validation against a metabolic cart, metabolic chamber) and 8 in a field and laboratory setting. Correlation coefficients between AM outcomes and energy expenditure (EE) by the criterion method (doubly labelled water and metabolic cart/chamber) and percentage mean differences between EE estimation from the monitor and EE measurement by the criterion method were extracted. Random-effects meta-analyses were performed to pool the results across studies where possible. Types of devices were compared using meta-regression analyses. Most validation studies had been performed in healthy adults (n=118), with few carried out in patients with chronic diseases (n=16). For total EE, correlation coefficients were statistically significantly lower in uniaxial compared to multisensor devices. For active EE, correlations were slightly but not significantly lower in uniaxial compared to triaxial and multisensor devices. Uniaxial devices tended to underestimate TEE (-12.07 (95%CI; -18.28 to -5.85) %) compared to triaxial (-6.85 (95%CI; -18.20 to 4.49) %, p=0.37) and were statistically significantly less accurate than multisensor devices (-3.64 (95%CI; -8.97 to 1.70) %, p

Background Guidance documents for the development and validation of patient-reported outcomes (PROs) advise the use of conceptual frameworks, which outline the structure of the concept that a PRO aims to measure. It is unknown whether currently available PROs are based on conceptual frameworks. This study, which was limited to a specific case, had the following aims: (i) to identify conceptual frameworks of physical activity in chronic respiratory patients or similar populations (chronic heart disease patients or the elderly) and (ii) to assess whether the development and validation of PROs to measure physical activity in these populations were based on a conceptual framework of physical activity. Methods Two systematic reviews were conducted through searches of the Medline, Embase, PsycINFO, and Cinahl databases prior to January 2010. Results In the first review, only 2 out of 581 references pertaining to physical activity in the defined populations provided a conceptual framework of physical activity in COPD patients. In the second review, out of 103 studies developing PROs to measure physical activity or related constructs, none were based on a conceptual framework of physical activity. Conclusions These findings raise concerns about how the large body of evidence from studies that use physical activity PRO instruments should be evaluated by health care providers, guideline developers, and regulatory agencies.

BackgroundLonger-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization.MethodsThis population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes.ResultsSymptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care.ConclusionsIn this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care.RegistrationISRCTN14990068

Fingolimod lowers the number of relapses in multiple sclerosis (MS) patients and slows down disease progression, but causes a broad spectrum of side effects. Our aim was to estimate the benefit-harm balance of fingolimod using individual patient data from FREEDOMS, a randomized controlled trial that compared two different dosages of fingolimod to placebo.We modelled the health status of patients over two years on a scale ranging from 0 (worst health or death) to 100 (maximum health). The model considered Expanded Disability Status Scale measurements, relapses and adverse events. We compared the mean health status between arms, and the proportion of trial participants for whom health declined or improved compared to baseline by a predefined minimal important difference of 4.6 or more.The main analysis showed a net benefit for fingolimod 0.5mg compared to placebo, with an average health status difference over two years of 2.7 (95% CI 2.2 to 3.2). Patients on fingolimod 0.5mg were 0.53 (95% CI 0.40-0.72, p0.001) times less likely to have a relevant decline in health status compared to patients on placebo, corresponding to a number needed to treat of 8 to prevent one relevant decline in health status. All sensitivity analyses favoured fingolimod 0.5mg.Although fingolimod's net benefit did not reach the clinical relevance on average, the decreased risk for a decline in health over two years may be relevant. This approach could be applied to other MS drugs and provide an objective evidence base for guideline recommendations.

Objectives: Seroprevalence studies to assess the spread of SARS-CoV-2 infection in the general population and subgroups are key for evaluating mitigation and vaccination policies and for understanding the spread of the disease both on the national level and for comparison with the international community. Methods: Corona Immunitas is a research program of coordinated, population-based, seroprevalence studies implemented by Swiss School of Public Health (SSPH+). Over 28,340 participants, randomly selected and age-stratified, with some regional specificities will be included. Additional studies in vulnerable and highly exposed subpopulations are also planned. The studies will assess population immunological status during the pandemic. Results: Phase one (first wave of pandemic) estimates from Geneva showed a steady increase in seroprevalence up to 10.8% (95% CI 8.2-13.9, n = 775) by May 9, 2020. Since June, Zurich, Lausanne, Basel City/Land, Ticino, and Fribourg recruited a total of 5973 participants for phase two thus far. Conclusions: Corona Immunitas will generate reliable, comparable, and high-quality serological and epidemiological data with extensive coverage of Switzerland and of several subpopulations, informing health policies and decision making in both economic and societal sectors. ISRCTN Registry: https://www.isrctn.com/ISRCTN18181860 ., + ID der Publikation: unilu_50428 + Sprache: Englisch + Letzte Aktualisierung: 2020-11-02 15:42:18

Objectives In Europe, there is uncertainty about the potential effects and cost-effectiveness of low dose computed tomography screening for lung cancer and about the applicability of results of North American studies. We aimed to estimate the effects and cost-effectiveness of lung cancer screening in a population-based setting in Switzerland where the smoking prevalence is high. Materials and methods The MIcrosimulation Screening ANalysis-Lung (MISCAN) model was adapted using country specific input parameters regarding lung cancer epidemiology, smoking behaviours, and treatment costs. The effects and costs of 648 screening scenarios with different screening start and stop ages, smoking eligibility criteria, and screening intervals were examined from a public healthcare system perspective across a lifetime horizon in a cohort born between 1935 and 1965. Results All screening scenarios showed an increase in the total number of detected lung cancer cases and a decrease in lung cancer mortality. On the efficiency frontier, 15 of 27 scenarios showed incremental cost-effectiveness ratios below € 50,000 per life year gained. These scenarios reduced lung cancer mortality by 6–15% while increasing incidence of lung cancer diagnoses by 2–6%. Conclusion These results suggest that lung cancer screening may be cost-effective in Switzerland, a high-income, European country with high smoking prevalence.

This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients.To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups.Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative.Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff.Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values.Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.

Background: There is a general notion that stressful life events may cause mental and physical health problems. Objectives: We aimed to describe stressful life events reported by patients with chronic obstructive pulmonary disease (COPD) and to assess their impact on health outcomes and behaviors. Methods: Two hundred and sixty-six primary care patients who participated in the ICE COLD ERIC cohort study were asked to document any stressful life events in the past 3 years. We assessed the before-after (the event) changes for symptoms of depression and anxiety, health status, dyspnea-related quality of life, exacerbations, cigarette use, and physical activity. We used linear regression analysis to estimate the crude and adjusted magnitude of the before-after changes. Results: About 41% (110/266) of patients reported the experience of any stressful life events and “death of relatives/important persons” was most common (31%). After accounting for age, sex, living status, lung function, and anxiety/depression status at baseline, experiencing any stressful life events was associated with a 0.9-point increase on the depression scale (95% CI 0.3 to 1.4), a 0.8-point increase on the anxiety scale (95% CI 0.3 to 1.3), and a 0.8-point decrease in the physical activity score (95% CI –1.6 to 0). Conclusions: Experiencing stressful life events was associated with a small to moderate increase in symptoms of depression and anxiety in COPD, but no discernable effect was found for other physical outcomes. However, confirmation of these results in other COPD cohorts and identification of patients particularly vulnerable to stressful life events are needed.

The treatment of symptomatic patients with chronic airway obstruction (defined by a forced expiratory volume in 1 s to forced vital capacity ratio of

Objectives In a previous project aimed at informing patient-centered care for people with multiple chronic conditions, we performed highly stratified quantitative benefit–harm assessments for 2 top priority questions. In this current work, our goal was to describe the process and approaches we developed and to qualitatively glean important elements from it that address patient-centered care. Methods We engaged patients, caregivers, clinicians, and guideline developers as stakeholder representatives throughout the process of the quantitative benefit–harm assessment and investigated whether the benefit–harm balance differed based on patient preferences and characteristics (stratification). We refined strategies to select the most applicable, valid, and precise evidence. Results Two processes were important when assessing the balance of benefits and harms of interventions: (1) engaging stakeholders and (2) stratification by patient preferences and characteristics. Engaging patients and caregivers through focus groups, preference surveys, and as co-investigators provided value in prioritizing research questions, identifying relevant clinical outcomes, and clarifying the relative importance of these outcomes. Our strategies to select evidence for stratified benefit–harm assessments considered consistency across outcomes and subgroups. By quantitatively estimating the range in the benefit–harm balance resulting from true variation in preferences, we clarified whether the benefit–harm balance is preference sensitive. Conclusions Our approaches for engaging patients and caregivers at all phases of the stratified quantitative benefit–harm assessments were feasible and revealed how sensitive the benefit–harm balance is to patient characteristics and individual preferences. Accordingly, this sensitivity can suggest to guideline developers when to tailor recommendations for specific patient subgroups or when to explicitly leave decision making to individual patients and their providers.

Background The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations. Methods We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes. Results In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile. Conclusions All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.

Background Patient preferences are key parameters to evaluate benefit-harm balance of statins for primary prevention but they are not readily available to guideline developers and decision makers. Our study aimed to elicit patient preferences for benefit and harm outcomes related to use of statins for primary cardiovascular disease prevention and to examine how the preferences differ across economically and socio–culturally different environments. Methods We conducted preference-eliciting surveys using best-worst scaling designed with a balanced incomplete-block design (BIBD) on 13 statins-related outcomes on 220 people in Ethiopia and Switzerland. The participants made tradeoff decisions and selected the most and least worrisome outcomes concurrently from each scenario generated using the BIBD. The design yielded 34,320 implied paired-comparisons and 2860 paired-responses as unit of analysis for eliciting the preferences that were analyzed using a conditional-logit model on a relative scale and surface under the cumulative ranking curve from multivariate random-effects meta-analysis model on a scale of 0 to 1. Results There was high internal consistency of responses and minimal amount of measurement error in both surveys. Severe stroke was the most worrisome outcome with a ceiling preference of 1 (on 0 to 1 scale) followed by severe myocardial infarction, 0.913 (95% CI, 0.889–0.943), and cancer, 0.846 (0.829–0.855); while treatment discontinuation, 0.090 (0.023–0.123), and nausea/headache, 0.060 (0.034–0.094) were the least worrisome outcomes. Preferences were similar between Ethiopia and Switzerland with overlapping uncertainty intervals and concordance correlation of 0.97 (0.90–0.99). Conclusions Our study provides much needed empirical evidence on preferences that help clinical guidelines consider for weighing the benefit and harm outcomes when recommending for or against statins for primary prevention of cardiovascular disease. The preferences are consistent across the disparate settings; however, we recommend inclusion of more countries in future studies to ensure the generalizability of the preferences to all environments. Electronic supplementary material The online version of this article (10.1186/s12872-018-0838-9) contains supplementary material, which is available to authorized users.

Background Prediction models and prognostic scores have been increasingly popular in both clinical practice and clinical research settings, for example to aid in risk-based decision making or control for confounding. In many medical fields, a large number of prognostic scores are available, but practitioners may find it difficult to choose between them due to lack of external validation as well as lack of comparisons between them. Methods Borrowing methodology from network meta-analysis, we describe an approach to Multiple Score Comparison meta-analysis (MSC) which permits concurrent external validation and comparisons of prognostic scores using individual patient data (IPD) arising from a large-scale international collaboration. We describe the challenges in adapting network meta-analysis to the MSC setting, for instance the need to explicitly include correlations between the scores on a cohort level, and how to deal with many multi-score studies. We propose first using IPD to make cohort-level aggregate discrimination or calibration scores, comparing all to a common comparator. Then, standard network meta-analysis techniques can be applied, taking care to consider correlation structures in cohorts with multiple scores. Transitivity, consistency and heterogeneity are also examined. Results We provide a clinical application, comparing prognostic scores for 3-year mortality in patients with chronic obstructive pulmonary disease using data from a large-scale collaborative initiative. We focus on the discriminative properties of the prognostic scores. Our results show clear differences in performance, with ADO and eBODE showing higher discrimination with respect to mortality than other considered scores. The assumptions of transitivity and local and global consistency were not violated. Heterogeneity was small. Conclusions We applied a network meta-analytic methodology to externally validate and concurrently compare the prognostic properties of clinical scores. Our large-scale external validation indicates that the scores with the best discriminative properties to predict 3 year mortality in patients with COPD are ADO and eBODE. Electronic supplementary material The online version of this article (doi:10.1186/s12874-017-0433-2) contains supplementary material, which is available to authorized users.

Background: Existing prediction models for mortality in chronic obstructive pulmonary disease (COPD) patients have not yet been validated in primary care, which is where the majority of patients receive care. Objectives: Our aim was to validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2-year mortality in 2 general practice-based COPD cohorts. Methods: Six hundred and forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV were enrolled by their general practitioners and followed for 2 years. The ADO regression equation was used to predict a 2-year risk of all-cause mortality in each patient and this risk was compared with the observed 2-year mortality. Discrimination and calibration were assessed as well as the strength of association between the 15-point ADO score and the observed 2-year all-cause mortality. Results: Fifty-two (8.1%) patients died during the 2-year follow-up period. Discrimination with the ADO index was excellent with an area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall, the predicted and observed risks matched well and visual inspection revealed no important differences between them across 10 risk classes (p = 0.68). The odds ratio for death per point increase according to the ADO index was 1.50 (95% CI 1.31-1.71). Conclusions: The ADO index showed excellent prediction properties in an out-of-population validation carried out in COPD patients from primary care settings.

Cross-sectional studies suggest an association of 25-hydroxyvitamin D with exacerbations in patients with COPD, but longitudinal evidence from cohort studies is scarce. The aim of this study was to assess the association of serum 25-hydroxyvitamin D with exacerbations and mortality in primary care patients with COPD. In the main analysis, we included 356 patients with COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages II-IV, free from exacerbations for ≥ 4 weeks) from a prospective cohort study in Dutch and Swiss primary care settings. We used negative binomial and Cox regression to assess the association of 25-hydroxyvitamin D with (centrally adjudicated) exacerbations and mortality, respectively. Baseline mean ± SD serum 25-hydroxyvitamin D concentration was 15.5 ± 8.9 ng/dL, and 274 patients (77.0%) had 25-hydroxyvitamin D deficiency ( 30 ng/dL, n = 24 [6.7%]), the risk was lower, although not significantly (incidence rate ratio, 0.72 [95% CI, 0.37-1.42]). In patients taking vitamin D supplements, using different cutoffs for 25-hydroxyvitamin D or competing risk models did not materially change the results. We did not find a statistically significant association of 25-hydroxyvitamin D concentration with mortality. This longitudinal study in a real-world COPD population that carefully minimized misclassification of exacerbations and the influence of confounding did not show an association of 25-hydroxyvitamin D with exacerbations and mortality

BACKGROUND: Guidelines have provided positive recommendations for pulmonary rehabilitation after exacerbations of chronic obstructive pulmonary disease (COPD), but recent studies indicate that postexacerbation rehabilitation may not always be effective in patients with unstable COPD. OBJECTIVES: To assess effects of pulmonary rehabilitation after COPD exacerbations on hospital admissions (primary outcome) and other patient‐important outcomes (mortality, health‐related quality of life (HRQL) and exercise capacity). SEARCH METHODS: We identified studies through searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PEDro (Physiotherapy Evidence Database) and the Cochrane Airways Review Group Register of Trials. Searches were current as of 20 October 2015, and handsearches were run up to 5 April 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing pulmonary rehabilitation of any duration after exacerbation of COPD versus conventional care. Pulmonary rehabilitation programmes had to include at least physical exercise (endurance or strength exercise, or both). We did not apply a criterion for the minimum number of exercise sessions a rehabilitation programme had to offer to be included in the review. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: We expected substantial heterogeneity across trials in terms of how extensive rehabilitation programmes were (i.e. in terms of number of completed exercise sessions; type, intensity and supervision of exercise training; and patient education), duration of follow‐up (< 3 months vs ≥ 3 months) and risk of bias (generation of random sequence, concealment of random allocation and blinding); therefore, we performed subgroup analyses that were defined before we carried them out. We used standard methods expected by Cochrane in preparing this update, and we used GRADE for assessing the quality of evidence. MAIN RESULTS: For this update, we added 11 studies and included a total of 20 studies (1477 participants). Rehabilitation programmes showed great diversity in terms of exercise training (number of completed exercise sessions; type, intensity and supervision), patient education (from none to extensive self‐management programmes) and how they were organised (within one setting, e.g. pulmonary rehabilitation, to across several settings, e.g. hospital, outpatient centre and home). In eight studies, participants completed extensive pulmonary rehabilitation, and in 12 studies, participants completed pulmonary rehabilitation ranging from not extensive to moderately extensive. Eight studies involving 810 participants contributed data on hospital readmissions. Moderate‐quality evidence indicates that pulmonary rehabilitation reduced hospital readmissions (pooled odds ratio (OR) 0.44, 95% confidence interval (CI) 0.21 to 0.91), but results were heterogenous (I(2) = 77%). Extensiveness of rehabilitation programmes and risk of bias may offer an explanation for the heterogeneity, but subgroup analyses were not statistically significant (P values for subgroup effects were between 0.07 and 0.11). Six studies including 670 participants contributed data on mortality. The quality of evidence was low, and the meta‐analysis did not show a statistically significant effect of rehabilitation on mortality (pooled OR 0.68, 95% CI 0.28 to 1.67). Again, results were heterogenous (I(2) = 59%). Subgroup analyses showed statistically significant differences in subgroup effects between trials with more and less extensive rehabilitation programmes and between trials at low and high risk for bias, indicating possible explanations for the heterogeneity. Hospital readmissions and mortality studies newly included in this update showed, on average, significantly smaller effects of rehabilitation than were seen in earlier studies. High‐quality evidence suggests that pulmonary rehabilitation after an exacerbation improves health‐related quality of life. The eight studies that used St George's Respiratory Questionnaire (SGRQ) reported a statistically significant effect on SGRQ total score, which was above the minimal important difference (MID) of four points (mean difference (MD) ‐7.80, 95% CI ‐12.12 to ‐3.47; I(2) = 64%). Investigators also noted statistically significant and important effects (greater than MID) for the impact and activities domains of the SGRQ. Effects were not statistically significant for the SGRQ symptoms domain. Again, all of these analyses showed heterogeneity, but most studies showed positive effects of pulmonary rehabilitation, some studies showed large effects and others smaller but statistically significant effects. Trials at high risk of bias because of lack of concealment of random allocation showed statistically significantly larger effects on the SGRQ than trials at low risk of bias. High‐quality evidence shows that six‐minute walk distance (6MWD) improved, on average, by 62 meters (95% CI 38 to 86; I(2) = 87%). Heterogeneity was driven particularly by differences between studies showing very large effects and studies showing smaller but statistically significant effects. For both health‐related quality of life and exercise capacity, studies newly included in this update showed, on average, smaller effects of rehabilitation than were seen in earlier studies, but the overall results of this review have not changed to an important extent compared with results reported in the earlier version of this review. Five studies involving 278 participants explicitly recorded adverse events, four studies reported no adverse events during rehabilitation programmes and one study reported one serious event. AUTHORS' CONCLUSIONS: Overall, evidence of high quality shows moderate to large effects of rehabilitation on health‐related quality of life and exercise capacity in patients with COPD after an exacerbation. Some recent studies showed no benefit of rehabilitation on hospital readmissions and mortality and introduced heterogeneity as compared with the last update of this review. Such heterogeneity of effects on hospital readmissions and mortality may be explained to some extent by the extensiveness of rehabilitation programmes and by the methodological quality of the included studies. Future researchers must investigate how the extent of rehabilitation programmes in terms of exercise sessions, self‐management education and other components affects the outcomes, and how the organisation of such programmes within specific healthcare systems determines their effects after COPD exacerbations on hospital readmissions and mortality.

Exercise tests are important to characterise chronic obstructive pulmonary disease patients and predict their prognosis, but are often not available outside of rehabilitation or research settings. Our aim was to assess the predictive performance of the sit-to-stand and handgrip strength tests. The prospective cohort study in Dutch and Swiss primary care settings included a broad spectrum of patients (n=409) with Global Initiative for Chronic Obstructive Lung Disease stages II to IV. To assess the association of the tests with outcomes, we used Cox proportional hazards (mortality), negative binomial (centrally adjudicated exacerbations) and mixed linear regression models (longitudinal health-related quality of life) while adjusting for age, sex and severity of disease. The sit-to-stand test was strongly (adjusted hazard ratio per five more repetitions of 0.58, 95% CI 0.40–0.85; p=0.004) and the handgrip strength test moderately strongly (0.84, 95% CI 0.72–1.00; p=0.04) associated with mortality. Both tests were also significantly associated with health-related quality of life but not with exacerbations. The sit-to-stand test alone was a stronger predictor of 2-year mortality (area under curve 0.78) than body mass index (0.52), forced expiratory volume in 1 s (0.61), dyspnoea (0.63) and handgrip strength (0.62). The sit-to-stand test may close an important gap in the evaluation of exercise capacity and prognosis of chronic obstructive pulmonary disease patients across practice settings., The 1-min sit-to-stand test predicts mortality in COPD patients and can easily be implemented across practice settings http://ow.ly/mxrPx