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Abstract: Musculoskeletal conditions are often managed in primary care settings. To facilitate research and healthcare quality, practice-based research networks offer sustained collaborations between clinicians and researchers. A scoping review was conducted to describe characteristics of practice-based research networks used for musculoskeletal research and musculoskeletal research conducted through practice-based research networks. Practice-based research networks were identified from 1) musculoskeletal-studies identified in OVID Medline, CINAHL, and Embase databases from inception to 5 February 2023 and in ClinicalTrials.gov and 2) from practice-based research network registries and websites. Among active musculoskeletal-focused practice-based research networks (i.e., currently recruiting and conducting research), an assessment of practice-based research network research good practices was performed. After screening 3025 records, 85 studies from 46 unique practice-based research networks met our eligibility criteria. Common conditions studied were low back pain (28%), musculoskeletal conditions not otherwise specified (25%), and osteoarthritis (19%). Thirty-two practice-based research networks (70%) were deemed to be active. Among active musculoskeletal-focused practice-based research networks, best practice data management information was retrievable for most (53%). Because of the scarcity of publicly available information, a large proportion of practice-based research network research good practice items was not assessable. Practice-based research networks have provided an avenue to assess clinical practice and patient outcomes related to musculoskeletal conditions. Further work to increase the transparency of musculoskeletal practice-based research network research practices is warranted., Competing Interests: Author disclosures: This work was internally supported with a grant to the University of Zurich from the Foundation for the Education of Chiropractors in Switzerland. The funders had no role in study conceptualization and design, or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the manuscript for publication. The authors declare no conflicts of interest and no financial incentives were provided. This work has not been previously presented in any form prior to this submission. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To define the concept of surgeon-scientists and identify the root causes of their decline in number and impact. The secondary aim was to provide actionable remedies., Background: Surgeons who conduct research in addition to patient care are referred to as «surgeon-scientists». While their value to society remains undisputed, their numbers and associated impact have been plunging. While reasons have been well identified along with proposals for countermeasures, their application have largely failed., Methods: We conducted a systematic review covering all aspects of surgeon-scientists together with a global online survey among 141 young academic surgeons. Using gap analysis, we determined implementation gaps for proposed measures. Then, we developed a comprehensive rescue package., Results: A surgeon-scientist must actively and continuously engage in both patient care and research. Competence in either field must be established through protected training and criteria of excellence, particularly reflecting contribution to innovation. The decline of surgeon-scientists has reached unprecedented magnitude. Leadership turning hospitals into «profit-factories» is one reason, a flawed selection process not exclusively based on excellence another. Most importantly, the appreciation for the academic mission has vanished. Along with fundamentally addressing these root causes, surgeon-scientists' path to excellence must be streamlined, and their continuous devotion for innovation cherished., Conclusion: The journey of the surgeon-scientist is at crossroads. As society, we either adapt and shift our priorities again towards innovation or capitulate to the greed for profit, permanently losing these invaluable professionals. Successful rescue packages must not only involve hospitals and universities but also the political sphere., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To provide improved guidance for the consistent application of the Clavien-Dindo classification (CDC) and Comprehensive Complication Index (CCI®) in challenging clinical scenarios., Background: Standardized outcome reporting is key for proper assessment of surgical procedures. A recent consensus conference recommended the CDC and the CCI® for assessing postoperative morbidity. Several challenging scenarios for grading complications still require evidence-based guidance, and the use of the two metrics in RCTs remains unexplored., Methods: We assessed the use of the CDC and CCI® as an outcome measure in a systematic literature search. Additionally, we asked 163 international surgeons to critically evaluate and independently grade complications in 20 complex clinical scenarios. Finally, a core group of five experts used this information to develop consistent recommendations., Results: Until July 2023, 1327 RCTs selected the CDC and/or CCI® to assess morbidity. Annual use was steadily increasing with now over 200 new RCTs per year. However, only a third (n=335) of published RCTs provided the complete range of CDC grades, including all subgrades. Eighty-nine out of 163 surgeons (response rate 55%) completed the questionnaire that served as basis for the recommendations: Repetitive interventions that are required to treat one complication, complications followed by further complications, complications occurring prior to referral, and expected and unrelated complications to the original procedure should all be counted separately and included in the CCI®. Invasive blank diagnostic interventions should not be considered a complication., Conclusion: The increasing use of the CDC and CCI® in RCTs highlights the importance of their standardized application. The current consensus on various difficult scenarios may offer novel guidance for the consistent use of the CDC and CCI®, aiming to improve complication reporting, and better-quality control, ultimately benefiting all healthcare stakeholders, and first and foremost, all patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To assess the current quality of surgical outcome reporting in the medical literature and to provide recommendations for improvement., Background: In 1996, The Lancet labeled surgery as a "comic opera" mostly referring to the poor quality of outcome reporting in the literature impeding improvement in surgical quality and patient care., Methods: We screened 3 first-tier and 2 second-tier surgical journals, as well as 3 leading medical journals for original articles reporting on results of surgical procedures published over a recent 18-month period. The quality of outcome reporting was assessed using a prespecified 12-item checklist., Results: Six hundred twenty-seven articles reporting surgical outcomes were analyzed, including 125 randomized controlled trials. Only 1 (0.2%) article met all 12 criteria of the checklist, whereas 356 articles (57%) fulfilled less than half of the criteria. The poorest reporting was on cumulative morbidity burden, which was missing in 94% of articles (n=591) as well as patient-reported outcomes missing in 83% of publications (n=518). Comparing journal groups for the individual criterion, we found moderate to very strong statistical evidence for better quality of reporting in high versus lower impact journals for 7 of 12 criteria and strong statistical evidence for better reporting of patient-reported outcomes in medical versus surgical journals ( P <0·001)., Conclusions: The quality of outcomes reporting in the medical literature remains poor, lacking improvement over the past 20 years on most key end points. The implementation of standardized outcome reporting is urgently needed to minimize biased interpretation of data thereby enabling improved patient care and the elaboration of meaningful guidelines., Competing Interests: P.A.C. developed the Clavien-Dindo classification. P.A.C. and M.A.P. developed the Comprehensive Complication Index (CCI). The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC., Methods: This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study., Discussion: This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC., Trial Registration: The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023., (© 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.)

Background: The benefit of Glucagon-like Peptide-1 (GLP-1) receptor agonists (RAs) in weight reduction against potential harms remains unclear. This study aimed at evaluating the benefit-harm balance of initiating GLP-1 RAs versus placebo for weight loss in people living with overweight and obesity but without diabetes., Methods: We performed benefit-harm balance modelling, which will be updated as new evidence emerges. We searched for randomised controlled trials (RCTs) in PubMed, controlled trials registry, drug approval and regulatory documents, and outcome preference weights as of April 10, 2024. We synthesize data using pairwise meta-analysis to estimate the effect of GLP-1 RAs to inform the benefit-harm balance modelling. We predicted the absolute effects of the positive and negative outcomes over 1 and 2 years of treatment using exponential models. We applied preference weights to the outcomes, ranging from 0 for least concerning to 1.0 for most concerning. We then calculated whether the benefit of achieving 5% and 10% weight loss outweighed the harms on a common scale. The analyses accounted for the statistical uncertainties of treatment effects, preference weights, and outcome risks., Findings: We included 8 RCTs involving 8847 participants. The pooled average age was 46.7 years, with the majority being women (74%) and people living with obesity (96%). Of 1000 persons treated with GLP-1 RAs for 2 years, 375 (95% confidence interval 352 to 399) achieved a 10% weight loss, and 318 (296 to 339) achieved a 5% weight loss compared to those treated with placebo. Several harm outcomes were more frequent in the GLP-1 RA group, including 41 abdominal pain events per 1000 persons over 2 years (19 to 69), cholelithiasis (8, 1 to 21), constipation (118, 78 to 164), diarrhoea (100, 42 to 173), alopecia (57, 10 to 176), hypoglycaemia (17, 1 to 68), injection site reactions (4, -3 to 19), and vomiting (110, 80 to 145) among others. Achieving a 10% weight loss with GLP-1 RA therapy outweighed the cumulative harms, with a net benefit probability of 0.97 at year 1 and 0.91 at year 2. The absolute net benefit was equivalent to 104 (100 to 112) per 1000 persons achieving a 10% weight loss over 2 years without experiencing any worrisome harm. A 5% weight loss did not show a net benefit, with probabilities of 0.13 and 0.01 at year 1 and year 2, respectively. However, these benefits were sensitive to preference weights, suggesting that even a 5% weight loss could be net beneficial for individuals with less concern about harm outcomes. The net benefit for a 10% weight loss was highest for semaglutide, followed by liraglutide and tirzepatide, with 2-year probabilities of 0.96, 0.72, and 0.60, respectively., Interpretation: The benefit of GLP-1 RAs exceeded the harms for weight loss in the first 2 years of treatment, yet the net benefit was dependent on individual' treatment goals (10% or 5% weight loss) and willingness to accept harms in pursuit of weight loss. This implies that treatment decisions have to be personalized to individuals to optimize benefits and reduce harms and overuse of treatments. Due to varying evidence, especially regarding harm outcomes across studies, it is necessary to continuously update and monitor the benefit-harm balance of GLP-1 RAs., Funding: SNSF and LOOP Zurich., Competing Interests: PG received payment as a speaker at symposia from Novo Nordisk and Eli Lilly. Other authors declare no competing interests., (© 2024 The Author(s).)

Introduction: Blinding is a methodologically important aspect in randomised controlled trials yet frequently overlooked in trials of spinal manual therapy interventions for back pain. To help inform the blinding methods of a future, double-placebo-controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain, we set four objectives: (1) to assess the feasibility of blinding participants, randomly allocated to an active or placebo-control spinal manual therapy intervention protocol, (2) to assess the feasibility of blinding outcome assessors within the trial, (3) to explore the influence of spinal manual therapy experience and low back pain on blinding, and (4) to explore factors contributing to perceptions about intervention assignment among participants and outcome assessors., Methods and Analysis: Two-parallel-group, single-centre, placebo-controlled, methodological blinding feasibility randomised trial. We will recruit between 60 and 100 adults with or without back pain and with or without experience of spinal manual therapy from Zurich, Switzerland. Participants will be randomised to either an active spinal manual therapy or a placebo-control spinal manual therapy protocol-both interventions delivered over two study visits, up to two weeks apart. The primary outcome is participant blinding using the Bang blinding index within each intervention arm immediately after each of the two study visits. Secondary outcomes are participant blinding using the James blinding index, outcome assessor blinding (Bang and James blinding indices), self-reported factors influencing perceived intervention assignment among participants and outcome assessors, and participant-reported credibility and expectancy of study interventions. Other outcomes-included to blind the study objective from participants-are lumbar spine range of motion, self-rated general health, satisfaction with care, pain intensity, and function. Intervention provider outcomes include intervention component fidelity and quality of intervention delivery., Ethics and Dissemination: The independent ethics commission of Canton Zurich granted ethical approval for this study (KEK 2023-00381). Written informed consent will be obtained from all participants. Findings will be disseminated in scientific conferences and a peer-reviewed publication and inform the blinding methods of a future double-placebo controlled trial comparing spinal manual therapy and nerve root injection for lumbosacral radicular pain-the SALuBRITY trial., Trial Registration: NCT05778396., (© 2024. The Author(s).)

Understanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological, and social factors in a large longitudinal population-based sample. Data was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort study Ciao Corona in Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc.), psychological (sadness, anxiousness, stress), and social (nationality, parents' education, etc.) factors, were assessed in 2020 and 2021 and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level. Median KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness, and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions, or nationality, were determinants only in individual subscales., Conclusion: Recent mental health, more than biological, physical, or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group., What Is Known: • Assessing health-related quality of life (HRQOL) in children and adolescents aids in understanding how life circumstances impact their well-being. • HRQOL is a complex construct, involving biological, psychological, and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples., What Is New: • Mental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors. • Public health strategies to improve mental health may be effective in improving HRQOL in children., (© 2024. The Author(s).)

Background: Machine learning (ML) has been successfully implemented for classification tasks (e.g., cancer diagnosis). ML performance for more challenging predictions is largely unexplored. This study's objective was to compare machine learning vs. expert-informed predictions for surgical outcome in patients undergoing major liver surgery., Methods: Single tertiary center data on preoperative parameters and postoperative complications for elective hepatic surgery patients were included (2008-2021). Expert-informed prediction models were established on 14 parameters identified by two expert liver surgeons to impact on postoperative outcome. ML models used all available preoperative patient variables (n = 62). Model performance was compared for predicting 3-month postoperative overall morbidity. Temporal validation and additional analysis in major liver resection patients were conducted., Results: 889 patients included. Expert-informed models showed low average bias (2-5 CCI points) with high over/underprediction. ML models performed similarly: average prediction 5-10 points higher than observed CCI values with high variability (95% CI -30 to 50). No performance improvement for major liver surgery patients., Conclusion: No clinical relevance in the application of ML for predicting postoperative overall morbidity was found. Despite being a novel hype, ML has the potential for application in clinical practice. However, at this stage it does not replace established approaches of prediction modelling., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Practice-based research networks are collaborations between clinicians and researchers to advance primary care research. This study aims to assess the feasibility for longitudinal data collection within a newly established chiropractic PBRN in Switzerland., Methods: A prospective observational cohort feasibility study was performed. PBRN participating chiropractors were asked to recruit patients seeking new conservative health care for musculoskeletal pain from March 28, 2022, to September 28, 2022. Participants completed clinically oriented survey questions and patient-reported outcome measures before the initial chiropractic assessment as well as 1 h, 2 weeks, 6 weeks, and 12 weeks thereafter. Feasibility was assessed through a variety of process, resource, and management metrics. Patient clinical outcomes were also assessed., Results: A total of 76 clinicians from 35 unique primary care chiropractic clinics across Switzerland participated. A total of 1431 patients were invited to participate, of which 573 (mean age 47 years, 51% female) were enrolled. Patient survey response proportions were 76%, 64%, 61%, and 56%, at the 1-h, 2-, 6-, and 12-week survey follow-ups, respectively. Evidence of an association was found between increased patient age (OR = 1.03, 95%CI 1.01-1.04), patient from a German-speaking region (OR = 1.81, 95%CI 1.17-2.86), non-smokers (OR = 1.89, 95%CI 1.13-3.17), and increased pain impact score at baseline (OR = 1.18, 95%CI 1.01-1.38) and response to all surveys., Conclusion: The Swiss ChiCo pilot study exceeded its prespecified feasibility objectives. Nationwide longitudinal data capture was highly feasible. Similar to other practice-based cohorts, participant retention remains a challenge. Trial registration Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020)., (© 2024. The Author(s).)

Teaching epidemiological concepts in academic settings poses a challenge due to the intricate nature of the discipline as both a science and a practice. Whereas traditional classroom-based teaching methods are commonly employed, evidence suggests they may not be the most effective approach for fostering core competencies and skills required in real-life scientific work. In this article, we describe our process of transitioning from traditional classroom teaching of epidemiology towards practice-based coaching to convey epidemiological concepts to bachelor's and master's students in Biomedicine. We chose the framework of randomized controlled trials (RCT) since they offer a great opportunity to teach epidemiological concepts in a hands-on course. This practice-based course encompasses the entire life cycle of a study, allowing students to design and conduct a short-term experiment, analyse its data and prepare a scientific paper. We provide a comprehensive overview of the course structure, content, learning objectives and course evaluation, while also discussing the advantages and disadvantages of this innovative format. Our approach offers a promising alternative to classroom teaching by incorporating practical, hands-on experiences offering students a high level of independence and self-determination, as well as facilitation and coaching by faculty. It has the potential to be applied across diverse academic settings, providing students with valuable skills and competencies in epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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.)

Objectives: To facilitate informed decision making on participating in colorectal cancer (CRC) screening, we assessed the benefit-harm balance of CRC screening for a wide range of subgroups over different time horizons., Methods: The study combined incidence proportions of benefits and harms of (not) participating in CRC screening estimated by the Adenoma and Serrated pathway to CAncer microsimulation model, a preference eliciting survey, and benefit-harm balance modeling combining all outcomes to determine the net health benefit of CRC screening over 10, 20, and 30 years. Probability of net health benefit was estimated for 210 different subgroups based on age, sex, previous participation in CRC screening, and lifestyle., Results: CRC screening was net beneficial in 183 of 210 subgroups over 30 years (median probability [MP] of 0.79, interquartile range [IQR] of 0.69-0.85) across subgroups. Net health benefit was greater for men (MP 0.82; IQR 0.69-0.89) than women (MP 0.76; IQR 0.67-0.83) and for those without history of participation in previous screenings (MP 0.84; IQR 0.80-0.89) compared with those with (MP 0.69; IQR 0.59-0.75). Net health benefit decreased with increasing age, from MP of 0.84 (IQR 0.80-0.86) at age 55 to 0.61 (IQR 0.56-0.71) at age 75. Shorter time horizons led to lower benefit, with MP of 0.70 (IQR 0.62-0.80) over 20 years and 0.54 (IQR 0.48-0.67) over 10 years., Conclusions: Our benefit-harm analysis provides information about net health benefit of screening participation, based on important characteristics and preferences of individuals, which could assist screening invitees in making informed decisions on screening participation., Competing Interests: Author Disclosures Links to the individual disclosure forms provided by the authors are available here., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The clinical validity of real-world walking cadence in people with COPD is unsettled. Our objective was to assess the levels, variability and association with clinically relevant COPD characteristics and outcomes of real-world walking cadence., Methods: We assessed walking cadence (steps per minute during walking bouts longer than 10 s) from 7 days' accelerometer data in 593 individuals with COPD from five European countries, and clinical and functional characteristics from validated questionnaires and standardised tests. Severe exacerbations during a 12-month follow-up were recorded from patient reports and medical registries., Results: Participants were mostly male (80%) and had mean±sd age of 68±8 years, post-bronchodilator forced expiratory volume in 1 s (FEV 1 ) of 57±19% predicted and walked 6880±3926 steps·day -1 . Mean walking cadence was 88±9 steps·min -1 , followed a normal distribution and was highly stable within-person (intraclass correlation coefficient 0.92, 95% CI 0.90-0.93). After adjusting for age, sex, height and number of walking bouts in fractional polynomial or linear regressions, walking cadence was positively associated with FEV 1, 6-min walk distance, physical activity (steps·day -1 , time in moderate-to-vigorous physical activity, vector magnitude units, walking time, intensity during locomotion), physical activity experience and health-related quality of life and negatively associated with breathlessness and depression (all p<0.05). These associations remained after further adjustment for daily steps. In negative binomial regression adjusted for multiple confounders, walking cadence related to lower number of severe exacerbations during follow-up (incidence rate ratio 0.94 per step·min -1 , 95% CI 0.91-0.99, p=0.009)., Conclusions: Higher real-world walking cadence is associated with better COPD status and lower severe exacerbations risk, which makes it attractive as a future prognostic marker and clinical outcome., Competing Interests: Conflict of interest: N. Karlsson reports owning stock in AstraZeneca, of which they are an employee; discourse made outside the submitted work. Conflict of interest: L. Palmerini reports being the co-founder of mHealth Technologies srl and owns shares of mHealth Technologies srl; disclosures made outside the submitted work. Conflict of interest: M.I. Polkey reports receiving consulting fees from Philips Respironics, outside the submitted work. Conflict of interest: D.A. Rodríguez Chiaradia reports grants or contracts from Janssen and Ferrer; consulting fees from Ferrer; payments for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ferrer and Janssen; support for attending meetings and/or travel from Ferrer, MSD and Janssen; and participation on a Data Safety Monitoring Board or Advisory Board for Janssen, all outside the submitted work. Conflict of interest: R. Rodriguez-Roisin reports grants or contracts from Chiesi and Beyond Air NO, outside the submitted work. Conflict of interest: I. Vogiatzis is an associate editor of this journal. Conflict of interest: T. Troosters reports grants or contracts from Mobilise-D IHI funding, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Numerous clinical parameters link to severe coronavirus disease 2019, but factors that prevent symptomatic disease remain unknown. We investigated the impact of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and endemic human coronavirus (HCoV) antibody responses on symptoms in a longitudinal children cohort ( n = 2,917) and a cross-sectional cohort including children and adults ( n = 882), all first exposed to SARS-CoV-2 (March 2020 to March 2021) in Switzerland. Saliva ( n = 4,993) and plasma ( n = 7,486) antibody reactivity to the four HCoVs (subunit S1 [S1]) and SARS-CoV-2 (S1, receptor binding domain, subunit S2 [S2], nucleocapsid protein) was determined along with neutralizing activity against SARS-CoV-2 Wuhan, Alpha, Delta, and Omicron (BA.2) in a subset of individuals. Inferred recent SARS-CoV-2 infection was associated with a strong correlation between mucosal and systemic SARS-CoV-2 anti-spike responses. Individuals with pre-existing HCoV-S1 reactivity exhibited significantly higher antibody responses to SARS-CoV-2 in both plasma (IgG regression coefficients = 0.20, 95% CI = [0.09, 0.32], P < 0.001) and saliva (IgG regression coefficient = 0.60, 95% CI = [0.088, 1.11], P = 0.025). Saliva neutralization activity was modest but surprisingly broad, retaining activity against Wuhan (median NT50 = 32.0, 1Q-3Q = [16.4, 50.2]), Alpha (median NT50 = 34.9, 1Q-3Q = [26.0, 46.6]), and Delta (median NT50 = 28.0, 1Q-3Q = [19.9, 41.7]). In line with a rapid mucosal defense triggered by cross-reactive HCoV immunity, asymptomatic individuals presented with higher pre-existing HCoV-S1 activity in plasma (IgG HKU1, odds ratio [OR] = 0.53, 95% CI = [0.29,0.97], P = 0.038) and saliva (total HCoV, OR = 0.55, 95% CI = [0.33, 0.91], P = 0.019) and higher SARS-CoV-2 reactivity in saliva (IgG S2 fold change = 1.26, 95% CI = [1.03, 1.54], P = 0.030). By investigating the systemic and mucosal immune responses to SARS-CoV-2 and HCoVs in a population without prior exposure to SARS-CoV-2 or vaccination, we identified specific antibody reactivities associated with lack of symptom development.IMPORTANCEKnowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020-2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses., Competing Interests: H.F.G. reports having received honoraria from Gilead Sciences, Merck, ViiV, GSK, Janssen, Johnson and Johnson, and Novartis for serving on DSMB and/or advisory boards and has received a travel grant from Gilead Sciences. In addition, he has received grants from the Swiss National Science Foundation (SNSF), the Swiss HIV Cohort Study, the Yvonne Jacob Foundation, and the NIH and unrestricted research grants from Gilead Sciences, all paid to the institution. A.T. has received honoraria from Roche Diagnostics for consultant activity, grants from the SNSF, the Swiss HIV Cohort Study, and the Pandemiefonds of the UZH foundation, and unrestricted research grants from Gilead Sciences. I.A.A. has received honoraria from MSD and Sanofi, a travel grant from Gilead Sciences, and a grant from Promedica foundation. R.D.K. has received grants from SNSF, the National Institutes of Health, and Gilead Sciences. C.P. has received a grant from the Collegium Helveticum.

Study Design: Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility., Background: Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment., Methods: On 7-8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from -1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating 'random guessing'-balanced 'active' and 'control' perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis., Results: 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, -0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (-0.12 to 0.30) and -0.10 (-0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment., Conclusions: Blinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed., Trial Registration: ClinicalTrials.gov: NCT05822947 (retrospectively registered)., (© 2024. The Author(s).)

Background: The Ready-To-Go (R2G) Questionnaire is a tool for rapid assessment of health risks for travel consultation. This study aims to assess the utility of the R2G Questionnaire in identifying high-risk travellers and predicting health events and behaviour during travel in the TOURIST2 prospective cohort., Methods: TOURIST2 data were used to calculate the R2G medical and travel risk scores and categorize each participant based on their risk. The TOURIST2 study enrolled 1000 participants from Switzerland's largest travel clinics between 2017 and 2019. Participants completed daily smartphone application surveys before, during and after travel on health events and behaviours. We used regression models to analyse incidence of overall health events and of similar health events grouped into health domains (e.g. respiratory, gastrointestinal, accident/injury). Incidence rate ratios (IRR) are displayed with 95% confidence intervals (95% CI)., Results: R2G high-risk travellers experienced significantly greater incidence of health events compared to lower-risk travellers (IRR = 1.27, 95% CI: 1.22-1.33). Both the medical and travel scores showed significant positive associations with incidence of health events during travel (IRR = 1.11, 95% CI: 1.07-1.16; IRR = 1.07, 95% CI: 1.03-1.12, respectively), with significant increases in all health domains except skin disorders. Medical and travel risk scores were associated with different patterns in behaviour. Travellers with chronic health conditions accessed medical care during travel more often (IRR = 1.16, 95% CI: 1.03-1.31), had greater difficulty in carrying out planned activities (IRR = -0.04, 95% CI: -0.05, -0.02), and rated their travel experience lower (IRR = -0.04, 95% CI: -0.06, -0.02). Travellers with increased travel-related risks due to planned travel itinerary had more frequent animal contact (IRR = 1.09, 95% CI: 1.01-1.18) and accidents/injuries (IRR = 1.28, 95% CI: 1.15-1.44)., Conclusions: The R2G Questionnaire is a promising risk assessment tool that offers a timesaving and reliable means to identify high-risk travellers. Incorporated into travel medicine websites, it could serve as a pre-consultation triage to help travellers self-identify their risk level, direct them to the appropriate medical provider(s), and help practitioners in giving more tailored advice., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Seroprevalence and the proportion of people with neutralizing activity (functional immunity) against SARS-CoV-2 variants were high in early 2022. In this prospective, population- based, multi-region cohort study, we assessed the development of functional and hybrid immunity (induced by vaccination and infection) in the general population during this period of high incidence of infections with Omicron variants., Methods: We randomly selected and assessed individuals aged ≥16 years from the general population in southern (n = 739) and north-eastern (n = 964) Switzerland in March 2022. We assessed them again in June/July 2022, supplemented with a random sample from western (n = 850) Switzerland. We measured SARS-CoV-2 specific IgG antibodies and SARS-CoV-2 neutralizing antibodies against three variants (ancestral strain, Delta, Omicron)., Results: Seroprevalence remained stable from March 2022 (97.6%, n = 1894) to June/July 2022 (98.4%, n = 2553). In June/July, the percentage of individuals with neutralizing capacity against ancestral strain was 94.2%, against Delta 90.8% and against Omicron 84.9%, and 50.6% developed hybrid immunity. Individuals with hybrid immunity had highest median levels of anti-spike IgG antibodies titres [4518 World Health Organization units per millilitre (WHO U/mL)] compared with those with only vaccine- (4304 WHO U/mL) or infection- (269 WHO U/mL) induced immunity, and highest neutralization capacity against ancestral strain (hybrid: 99.8%, vaccinated: 98%, infected: 47.5%), Delta (hybrid: 99%, vaccinated: 92.2%, infected: 38.7%) and Omicron (hybrid: 96.4%, vaccinated: 79.5%, infected: 47.5%)., Conclusions: This first study on functional and hybrid immunity in the Swiss general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less so for the general population., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Genetic defects in the interferon (IFN) system or neutralizing autoantibodies against type I IFNs contribute to severe COVID-19. Such autoantibodies were proposed to affect post-COVID-19 syndrome (PCS), possibly causing persistent fatigue for >12 weeks after confirmed SARS-CoV-2 infection. In the current study, we investigated 128 patients with PCS, 21 survivors of severe COVID-19, and 38 individuals who were asymptomatic. We checked for autoantibodies against IFN-α, IFN-β, and IFN-ω. Few patients with PCS had autoantibodies against IFNs but with no neutralizing activity, indicating a limited role of type I IFNs in PCS pathogenesis. In a subset consisting of 28 patients with PCS, we evaluated IFN-stimulated gene activity and showed that it did not correlate with fatigue. In conclusion, impairment of the type I IFN system is unlikely responsible for adult PCS., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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).)

Background: Tackling physical inactivity represents a key global public health challenge. Strategies to increase physical activity (PA) are therefore warranted. Despite the rising availability of digital interventions (DIs), which offer tremendous potential for PA promotion, there has been inadequate attention to the special needs of older adults., Objective: The aim was to investigate community-dwelling older adults' needs, requirements, and preferences toward DIs to promote PA., Methods: The target population of this cross-sectional study was community-dwelling older adults (≥60 years old) within German-speaking Switzerland. Potential respondents were informed about the study and sent a link to a self-developed and self-administered online survey by our cooperating institutions., Results: Overall, 922 respondents who completed the online survey were included in the final analysis. The mean age of the sample was 72 years (SD 6.4, range 60-98). The preferred delivery mode of DIs to promote PA was a website (428/922, 46.4%) and 80.3% (740/922) preferred video-based structures. Most respondents expressed the need for personal access, personal goals, personal messages, and a personal contact in case of problems or questions (585/817, 71.6%; 546/811, 67.3%; 536/822, 65.2%; 536/822, 65.2%). Memory training, psychological wellbeing, and nutrition were mainly rated as relevant additional content of DIs to promote PA (690/849, 81.2%; 661/845, 78.2%, 619/849, 72.9%)., Conclusion: Community-dwelling older adults may be willing to use DIs to promote PA in the long term, but this study identified particular needs and requirements in terms of design, technological realization, delivery mode, support, and individualization/personalization among the sample. Our results can inform future developments of DIs to promote PA specifically tailored to older adults. However, caution is warranted in interpreting the findings due to the sample's high PA and education levels., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Purpose: We aimed to assess the seroprevalence trends of SARS-CoV-2 antibodies in several Swiss cantons between May 2020 and September 2021 and investigate risk factors for seropositivity and their changes over time., Methods: We conducted repeated population-based serological studies in different Swiss regions using a common methodology. We defined three study periods: May-October 2020 (period 1, prior to vaccination), November 2020-mid-May 2021 (period 2, first months of the vaccination campaign), and mid-May-September 2021 (period 3, a large share of the population vaccinated). We measured anti-spike IgG. Participants provided information on sociodemographic and socioeconomic characteristics, health status, and adherence to preventive measures. We estimated seroprevalence with a Bayesian logistic regression model and the association between risk factors and seropositivity with Poisson models., Results: We included 13,291 participants aged 20 and older from 11 Swiss cantons. Seroprevalence was 3.7% (95% CI 2.1-4.9) in period 1, 16.2% (95% CI 14.4-17.5) in period 2, and 72.0% (95% CI 70.3-73.8) in period 3, with regional variations. In period 1, younger age (20-64) was the only factor associated with higher seropositivity. In period 3, being aged ≥ 65 years, with a high income, retired, overweight or obese or with other comorbidities, was associated with higher seropositivity. These associations disappeared after adjusting for vaccination status. Seropositivity was lower in participants with lower adherence to preventive measures, due to a lower vaccination uptake., Conclusions: Seroprevalence sharply increased over time, also thanks to vaccination, with some regional variations. After the vaccination campaign, no differences between subgroups were observed., (© 2023. The Author(s).)

Viruses have been present during all evolutionary steps on earth and have had a major effect on human history. Viral infections are still among the leading causes of death. Another public health concern is the increase of non-communicable metabolic diseases in the last four decades. In this Review, we revisit the scientific evidence supporting the presence of a strong bidirectional feedback loop between several viral infections and metabolic diseases. We discuss how viruses might lead to the development or progression of metabolic diseases and conversely, how metabolic diseases might increase the severity of a viral infection. Furthermore, we discuss the clinical relevance of the current evidence on the relationship between viral infections and metabolic disease and the present and future challenges that should be addressed by the scientific community and health authorities., Competing Interests: Declaration of interests NP reports consulting fees from Bayer Vital GmbH, speaker honoraria and travel support from Novo Nordisk, and speaker honoraria from GWT outside the submitted work. BGH is a member of the Gene Therapy Working Group, a permanent working group of the Swiss Expert Committee for Biosafety. NT is a member of the steering committee of the German Society for Pediatric Infectious Diseases. IAA reports grants from the Promedica foundation, consulting fees from Sanofi, speaker honoraria from MSD, and travel support from Gilead. PAG reports consulting fees and travel support from Novo Nordisk, consulting fees from Amgen, speaker honoraria from Eli Lilly, and is the President of the Swiss Association for the Study of Metabolism and Obesity. GM reports consulting fees from Novo Nordisk and Fractyl Health; participates on a data safety monitoring board or advisory board at Novo Nordisk, Fractyl Health, Recor, Metadeq, Keyron, and GHP Scientific; reports grants from Boehringer Ingelheim, and receives advisory board and speaker honoraria from Novo Nordisk and Boehringer Ingelheim. TC received grants from the European Research Council, Deutsche Forschungsgemeinschaft, US National Institutes of Health, Else Kröner Fresenius Center for Digital Health Dresden, Bundesministerium für Bildung und Forschung, German Center for Diabetes Research, and Sächsisches Staatsministerium für Wissenschaft, Kultur und Tourismus. All other authors report no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To describe the frequency of and reasons for changes in healthcare utilization in those requiring ongoing treatment, and to assess characteristics associated with change, during the second wave of the pandemic. Methods: Corona Immunitas e-cohort study (age ≥20 years) participants completed monthly questionnaires. We compared participants reporting a change in healthcare utilization with those who did not using descriptive and bivariate statistics. We explored characteristics associated with the number of changes using negative binomial regression. Results: The study included 3,190 participants from nine research sites. One-fifth reported requiring regular treatment. Among these, 14% reported a change in healthcare utilization, defined as events in which participants reported that they changed their ongoing treatment, irrespective of the reason. Reasons for change were medication changes and side-effects, specifically for hypertension, or pulmonary embolism treatment. Females were more likely to report changes [Incidence Rate Ratio (IRR) = 2.15, p = 0.002]. Those with hypertension were least likely to report changes [IRR = 0.35, p = 0.019]. Conclusion: Few of those requiring regular treatment reported changes in healthcare utilization. Continuity of care for females and chronic diseases besides hypertension must be emphasized., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Harju, Speierer, Jungo, Levati, Baggio, Tancredi, Noor, Rodondi, Cullati, Imboden, Keidel, Witzig, Frank, Kohler, Kahlert, Crivelli, Amati, Albanese, Kaufmann, Frei, von Wyl, Puhan, Probst-Hensch, Michel, Rodondi and Chocano-Bedoya.)

Objectives: We investigated changes in adherence to physical activity (PA) and screen time (ST) recommendations of children and adolescents throughout the pandemic, and their association with health-related quality of life (HRQOL). Methods: 1,769 primary (PS, grades 1-6) and secondary (SS, 7-9) school children from Ciao Corona, a school-based cohort study in Zurich, Switzerland, with five questionnaires 2020-2022. HRQOL was assessed using the KINDL questionnaire. PA (≥60 min/day moderate-to-vigorous PA) and ST (≤2 h/day ST) recommendations followed WHO guidelines. Results: Adherence to PA recommendations dropped in 2020 (83%-59% PS, 77%-52% SS), but returned to pre-pandemic levels by 2022 (79%, 66%). Fewer children met ST recommendations in 2020 (74% PS, 29% SS) and 2021 (82%, 37%) than pre-pandemic (95%, 68%). HRQOL decreased 3 points between 2020 and 2022, and was 9.7 points higher (95% CI 3.0-16.3) in March 2021 in children who met both versus no recommendations. Conclusion: Adherence to WHO guidelines on PA and ST during the pandemic had a consistent association with HRQOL despite longitudinal changes in behavior., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Haile, Gunz, Peralta, Ulytė, Raineri, Rueegg, Yasenok, Radtke, Puhan and Kriemler.)

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).)

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19., (© 2023. The Author(s).)

Background: Despite strong recommendations for coronavirus disease 2019 (Covid-19) vaccination by multiple sclerosis (MS) organizations, some persons with MS (pwMS) remain vaccine hesitant. The Swiss MS Registry conducted a survey to explore Covid-19 vaccine hesitancy, self-reported side effects and changes in MS symptoms following vaccination in adult pwMS., Methods: Self-reported data were analyzed cross-sectionally. Multivariable logistic regression was used to explore participant characteristics associated with Covid-19 vaccine hesitancy., Results: Of 849 respondents, 73 (8.6%) were unvaccinated. Hesitation to vaccinate was most often a personal preference (N = 42, 57.53%). Factors negatively associated with vaccine hesitancy included older age (OR = 0.97 per year, 95% CI [0.94, 0.99]) and regularly seeing healthcare professionals (OR = 0.25, 95% CI [0.07, 0.85]). A history of confirmed Covid-19 infection (OR = 3.38, 95% CI [1.69, 6.77]) and being underweight (OR = 4.50, 95% CI [1.52, 13.36]) were positively associated with vaccine hesitancy. Of 768 participants who provided information, 320 (41.2%) and 351 (45.2%) reported vaccination side effects after the first and second vaccinations, respectively. Changes in MS symptoms were reported by 49 (6.3%) participants after the first and 67 (9.0%) participants after the second vaccination, and were most often described as increased or new-onset fatigue (N = 17/49 (34.7%) after the first and N = 21/67 (31.3%) after the second dose)., Conclusions: Covid-19 vaccine hesitancy was low among surveyed pwMS. The risk of vaccine hesitancy was higher among younger pwMS, those with a history of Covid-19 infection, and those without regular contact with healthcare professionals., Competing Interests: Declaration of Competing Interest Mina Stanikić reports employment by Roche branch in Serbia, Roche d.o.o., from February 2019 to February 2020. Christian P Kamm has received honoraria for lectures as well as research support from Biogen, Novartis, Almirall, Teva, Merck, Sanofi Genzyme, Roche, Janssen, Eli Lilly, Celgene and the Swiss MS Society. Ente Ospedaliero Cantonale (employer) received compensation for Chiara Zecca's speaking activities, consulting fees, or research grants from Almirall, Biogen Idec, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sanofi, Teva Pharma, Roche. Chiara Zecca is recipient of a grant for senior researchers provided by AFRI (Area Formazione accademica, Ricerca e Innovazione), EOC. Ente Ospedaliero Cantonale (employer) received compensation for Claudio Gobbi's speaking activities, consulting fees, or research grants from Almirall, Biogen Idec, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sanofi, Teva Pharma, Roche. Anke Salmen has received speaker honoraria and/or travel compensation for activities with Bristol Myers Squibb, Novartis, Roche and research support of Baasch Medicus Foundation and the Swiss MS society, not related to this work. Andrew Chan has served on advisory boards for, and received funding for travel or speaker honoraria from Actelion-Janssen, Almirall, Bayer, Biogen, Celgene, Sanofi-Genzyme, Merck, Novartis, Roche and Teva, all for hospital research funds; and research support from Biogen, Genzyme and UCB. Eric Twomey, Milo A. Puhan, Vladeta Ajdacic-Gross and Viktor von Wyl declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

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: To describe and assess the risk of bias of the primary input studies that underpinned the Global Burden of Disease Study (GBD) 2019 modelled prevalence estimates of low back pain (LBP), neck pain (NP), and knee osteoarthritis (OA), from Australia, Brazil, Canada, Spain, and Switzerland. To evaluate the certainty of the GBD modelled prevalence evidence. Methods: Primary studies were identified using the GBD Data Input Sources Tool and their risk of bias was assessed using a validated tool. We rated the certainty of modelled prevalence estimates based on the GRADE Guidelines 30-the GRADE approach for modelled evidence. Results: Seventy-two primary studies (LBP: 67, NP: 2, knee OA: 3) underpinned the GBD estimates. Most studies had limited representativeness of their study populations, used suboptimal case definitions and applied assessment instruments with unknown psychometric properties. The certainty of modelled prevalence estimates was low, mainly due to risk of bias and indirectness. Conclusion: Beyond the risk of bias of primary input studies for LBP, NP, and knee OA in GBD 2019, the certainty of country-specific modelled prevalence estimates still have room for improvement., Competing Interests: JML, CAH, RDP, and BD report support for attending a meeting of the European Cooperation in Science and Technology – COST Action CA18218 (European Burden of Disease Network). JML, CAH, RDP, JVS, GMAW, and BD are members of the European COST Action CA18218. CAH and MAP report grants from the Swiss National Science Foundation (SNSF) and the European Centre for Chiropractic Research Excellence (ECCRE) outside the submitted work. The remaining author declares that they do not have any conflicts of interest., (Copyright © 2023 Muñoz Laguna, Puhan, Rodríguez Artalejo, De Pauw, Wyper, Devleesschauwer, Santos and Hincapié.)

Introduction: Sexuality, an important aspect of quality of life, is often overlooked in COPD. Our aim was to develop an instrument that facilitates communication and counseling on sexuality in persons living with chronic obstructive pulmonary disease (COPD)., Methods: We searched for publications on sexuality in COPD focusing on communication about sexuality and tools to support such communication. We also performed a survey asking 25 patients and 36 health care professionals (HCPs) about their attitudes, experiences, barriers, and facilitators when talking about sexuality. We set up a project expert team of HCPs and 3 persons with COPD. In a half-day workshop, the team discussed the results of the literature review and the survey as a basis for the contents, the "when and how" to address communication about sexuality, and the design of the communication instrument., Results: The survey showed that although patients and HCPs wanted to talk about sexuality, it rarely happened due to communication barriers, lack of self-confidence, and misconceptions on both sides. In review rounds of the expert team, feedback on the drafts was collected and integrated into the final version of the communication instrument: COmmunication about SexualitY in COPD (COSY). The COSY instrument resulted in 4 tools: a communication leaflet, an application guide, a pictorial representation of the spectrum of intimacy for HCPs, and a comprehensible, picturized information booklet for patients., Conclusions: Addressing sexuality in persons living with COPD should not be neglected. The COSY instrument could help to start and shape communication and consultations about sexuality and a more holistic consideration of quality of life., (JCOPDF © 2023.)

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).)

The Swiss chiropractic practice-based research network (PBRN) is a nationwide project developed in collaboration with patients, clinicians, and academic stakeholders to advance musculoskeletal epidemiologic research. The aim of this study was to describe the clinician population recruited and representativeness of this PBRN to inform future collaboration. A population-based cross-sectional study was performed. PBRN clinician characteristics were described and factors related to motivation (operationalised as VAS score ≥ 70) to participate in a subsequent patient cohort pilot study were assessed. Among 326 eligible chiropractors, 152 enrolled in the PBRN (47% participation). The PBRN was representative of the larger Swiss chiropractic population with regards to age, language, and geographic distribution. Of those enrolled, 39% were motivated to participate in a nested patient cohort pilot study. Motivation was associated with age 40 years or older versus 39 years or younger (OR 2.3, 95% CI 1.0-5.2), and with a moderate clinic size (OR 2.4, 95% CI 1.1-5.7) or large clinic size (OR 2.8, 95% CI 1.0-7.8) versus solo practice. The Swiss chiropractic PBRN has enrolled almost half of all Swiss chiropractors and has potential to facilitate collaborative practice-based research to improve musculoskeletal health care quality.Trial registration: Swiss chiropractic PBRN (ClinicalTrials.gov identifier: NCT05046249); Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020)., (© 2023. The Author(s).)

Postoperative complications represent a major public health burden worldwide. Without standardized, clinically relevant and universally applied endpoints, the evaluation of surgical interventions remains ill-defined and inconsistent, opening the door for biased interpretations and hampering patient-centered health care delivery. We conducted a Jury-based consensus conference incorporating the perspectives of different stakeholders, who based their recommendations on the work of nine panels of experts. The recommendations cover the selection of postoperative outcomes from the perspective of patients and other stakeholders, comparison and interpretation of outcomes, consideration of cultural and demographic factors, and strategies to deal with unwarranted outcomes. With the recommendations developed exclusively by the Jury, we provide a framework for surgical outcome assessment and quality improvement after medical interventions, that integrates the main stakeholders' perspectives., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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).)

Introduction: COVID-19 infection can impact the central nervous system, and is often associated with cognitive decline. However, there are no studies linking serologically confirmed COVID-19 infection with objectively assessed cognitive functioning. We explored whether presence of SARS-CoV-2 antibodies account for variability in participants' scores on a neuropsychological assessment., Methods: In this cross-sectional study participants were 657 (mean age = 72.97; SD = 6.07 years; women = 47.7%) individuals randomly selected from the general population of the canton of Zurich and included in the Corona Immunitas study. We conducted serological tests between October 2020 and May 2021 to detect and quantify SARS-CoV-2 antibodies in peripheral venous blood samples. We assessed cognitive function, vaccination status (vaccinated; not vaccinated), number of health conditions, and demographic variables between January and August 2021. We studied the association between seropositivity and global cognitive function and five cognitive domains (language expression, language comprehension, temporal orientation, spatial orientation, and memory) with linear regression models. Based on SARS-CoV-2 antibodies and vaccination status, we stratified participants into three groups: No SARS-CoV-2 antibodies ( N  = 402); SARS-CoV-2 antibodies due to vaccination ( N  = 218); history of SARS-CoV-2 infection and no vaccination ( N  = 37)., Results: In the regression model adjusted for age, sex, educational level, and number of health conditions, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to vaccination had better global cognitive functioning (Standardized beta = 0.10; 95% CI = 0.02; 0.17), and those with SARS-CoV-2 antibodies due to infection had poorer cognitive functioning (Standardized beta = -0.10; 95% CI = -0.18; -0.03). Regarding cognitive domains, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to infection scored more poorly on language comprehension and temporal orientation, and those with SARS-CoV-2 antibodies due to vaccination scored better on memory., Discussion: By linking serologically confirmed presence of SARS-CoV-2 antibodies to poorer global cognitive functioning in community dwelling older adults we strengthen existing evidence in support of cognitive decline related to COVID-19. Given the large number of infected older adults, and the endurance of the pandemic, our results highlight the need to address COVID-19 related cognitive decline in the clinical and public health areas of prevention, diagnosis, and treatment., 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 © 2023 Sabatini, Pacifico, Frei, Graf, Puhan and Albanese.)

Aims: To explore the effects of prices and flavour availability on the appeal of different tobacco and nicotine products, including conventional cigarettes, Electronic Nicotine Delivery Systems (ENDS) and Heated Tobacco Systems (HTS) among an adult population in Switzerland., Methods: We performed a Discrete Choice Experiment among a group of Swiss aged ≥18 years via the online recruiting platform Prolific in a convenience sample. Our sample included both non-smokers and smokers. We used a within-subject, alternative-specific block design in a series of choice sets including different smoking products. We fixed the attributes of nicotine content (high or medium) and harmfulness (in years of life lost) for each product. Attributes of interest included price (ranging from CHF 5 to 25 in increments of 5) and flavour (fruity/menthol vs none/tobacco flavour). We performed a conditional logistic regression on the attributes' influence on the appeal of cigarettes, ENDS and HTS., Results: A total of 108 out of 153 participants (n = 25 smokers and n = 83 non-smokers, completion rate = 71%) successfully completed our pilot survey experiment. We found that, in general, increasing the price of combustible cigarettes, ENDS and HTS by one standard deviation (around CHF 7) reduced their appeal by approximately 66% (relative risk [RR]: 0.34; 95% CI: 0.28-0.42). Unflavoured alternative nicotine products were found to be less appealing than flavoured products, especially for non-smokers, with a 86% decrease in appeal (RR: 0.14; 95% CI: 0.13-0.16). For non-smokers, an increase in price by one standard deviation was associated with a decrease in the appeal of any product by approximately 19% (RR: 0.81; 95% CI: 0.72-0.92). For smokers, the effect sizes were smaller, but overall, the appeal of all products decreased with increasing prices and reduced flavours., Conclusions: Our Discrete Choice Experiment suggests that, for the Swiss context, limiting the availability of flavours for alternative smoking products has the potential to reduce their appeal to non-smokers by 86% and that a small but significant increase in prices to CHF 15 for cigarettes, ENDS and HTS could lead to a major (around 66%) decrease in their appeal.

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.)

Introduction: Many countries have implemented indoor smoking bans over the past two decades. Although smoking bans have been shown to reduce cardiovascular outcomes, little is known about their impact on respiratory health. This study investigated the impact of a nationwide indoor smoking ban on smoking behaviour and lung function., Methods: We used repeated cross-sectional data from two large cohorts of the general population comprising 31 807 Swiss and 62 093 Danish adults. We compared associations between smoking ban and smoking prevalence and prebronchodilator lung function trends in Denmark (indoor smoking ban introduced in 2007) and Switzerland (indoor smoking ban introduced in 2010) from 2005 to 2010 using a quasi-experimental study design. We performed difference-in-difference analyses with linear regression models adjusted for age, sex, weight and height., Results: Denmark had a stronger decrease in active smokers compared with Switzerland. Also, forced expiratory volume in the first second was higher in Danish adults than in Swiss adults: 26 mL (95% CI 2.4 to 49) 1 year, 88 mL (65 to 112) 2 years, and 74 mL (51 to 98) 3 years after smoking ban implementation. Correspondingly, forced vital capacity was higher in Danish adults compared with Swiss adults (80 mL (50 to 109) after 1 year and 126 mL (97 to 155) after two and 3 years). Improvements were observed in both never-smokers and ever-smokers, most pronounced in ever-smokers., Conclusions: Nationwide indoor smoking ban is associated with less smoking and improved lung function in the general population. Implementing an indoor smoking ban can improve lung function by influencing smoking behaviour and reducing secondhand smoke., Competing Interests: Competing interests: YÇ reports personal fees from Boehringer Ingelheim, AstraZeneca, and Sanofi Genzyme outside of the submitted work. MSB reports grants from the European Commission’s H2020 and EiT Health programmes outside of the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Personalizing preventive therapies for atherosclerotic cardiovascular disease (ASCVD) is particularly important for older adults, as they tend to have multiple chronic conditions, increased risk for medication adverse effects, and may have heterogenous preferences when weighing health outcomes. However, little is known about outcome preferences related to ASCVD preventive therapies in older adults., Methods: In May 2021, using an established online panel, KnowledgePanel, we surveyed older US adults aged 65-84 years without history of ASCVD on outcome preferences related to statin therapy (benefit outcomes to be reduced by the therapy: heart attack, stroke; adverse effects: diabetes, abnormal liver test, muscle pain) or aspirin therapy (benefit outcomes: heart attack, stroke; adverse effects: brain bleed, bowel bleed, stomach ulcer). We used standardized best-worst scores (range of -1 for "least worrisome" to +1 for "most worrisome") and conditional logistic regression to examine the relative importance of the outcomes., Results: In this study, 607 ASCVD-free participants (median age 74, 46% male, 81% White) were included; 304 and 303 completed the statin and aspirin versions of the survey, respectively. For statin-related outcomes, stroke and heart attack were most worrisome (score 0.55; 95% CI 0.51, 0.60) and (0.53; 0.48, 0.58), followed by potential harms of diabetes (-0.07; -0.10, -0.03), abnormal liver test (-0.25; -0.29, -0.20), and muscle pain (-0.77; -0.82, -0.73). For aspirin-related outcomes, stroke and heart attack were similarly most worrisome (0.48; 0.43, 0.52) and (0.43; 0.38, 0.48), followed by brain bleed (0.30; 0.25, 0.34), bowel bleed (-0.31; -0.33, -0.28), and stomach ulcer (-0.90; -0.92, -0.87). Conditional logistic regression and subgroup analyses by age, sex, and race yielded similar results., Conclusions: Older adults generally consider outcomes related to benefits of ASCVD primary preventive therapies-stroke and heart attack-more important than their adverse effects. Integrating patient preferences with risk assessment is an important next step for personalizing ASCVD preventive therapies for older adults., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests, (© 2023 The Author(s).)

Background: Much remains unknown regarding the evolution of SARS-CoV-2 seroprevalence and variability in seropositive children in districts, schools and classes as only a few school-based cohort studies exist. Vaccination of children, initiated at different times for different age groups, adds additional complexity to the understanding of how seroprevalence developed in the school aged population., Aim: We investigated the evolution of SARS-CoV-2 seroprevalence in children and its variability in districts, schools and classes in Switzerland from June/July 2020 to November/December 2021., Methods: In this school-based cohort study, SARS-CoV-2 antibodies were measured in primary and secondary school children from randomly selected schools in the canton of Zurich in October/November 2020, March/April 2021 and November/December 2021. Seroprevalence was estimated using Bayesian logistic regression to adjust for test sensitivity and specificity. Variability of seroprevalence between school classes was expressed as maximum minus minimum seroprevalence in a class and summarised as median (interquartile range)., Results: 1875 children from 287 classes in 43 schools were tested, with median age 12 years (range 6-17), 51% 12+ vaccinated. Seroprevalence increased from 5.6% (95% credible interval [CrI] 3.5-7.6%) to 31.1% (95% CrI 27.0-36.1%) in unvaccinated children, and 46.4% (95% CrI 42.6-50.9%) in all children (including vaccinated). Earlier in the pandemic, seropositivity rates in primary schools were similar to or slightly higher (<5%) than those in secondary schools, but by late 2021, primary schools had 12.3% (44.3%) lower seroprevalence for unvaccinated (all) subjects. Variability in seroprevalence among districts and schools increased more than two-fold over time, and in classes from 11% (95% CrI 7-17%) to 40% (95% CrI 22-49%)., Conclusions: Seroprevalence in children increased greatly, especially in 2021 following introduction of vaccines. Variability in seroprevalence was high and increased substantially over time, suggesting complex transmission chains.

Background: walking is crucial for an active and healthy ageing, but the perspectives of individuals living with walking impairment are still poorly understood., Objectives: to identify and synthesise evidence describing walking as experienced by adults living with mobility-impairing health conditions and to propose an empirical conceptual framework of walking experience., Methods: we performed a systematic review and meta-ethnography of qualitative evidence, searching seven electronic databases for records that explored personal experiences of walking in individuals living with conditions of diverse aetiology. Conditions included Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture, heart failure, frailty and sarcopenia. Data were extracted, critically appraised using the NICE quality checklist and synthesised using standardised best practices., Results: from 2,552 unique records, 117 were eligible. Walking experience was similar across conditions and described by seven themes: (i) becoming aware of the personal walking experience, (ii) the walking experience as a link between individuals' activities and sense of self, (iii) the physical walking experience, (iv) the mental and emotional walking experience, (v) the social walking experience, (vi) the context of the walking experience and (vii) behavioural and attitudinal adaptations resulting from the walking experience. We propose a novel conceptual framework that visually represents the walking experience, informed by the interplay between these themes., Conclusion: a multi-faceted and dynamic experience of walking was common across health conditions. Our conceptual framework of the walking experience provides a novel theoretical structure for patient-centred clinical practice, research and public health., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Lung cancer is the leading cause of cancer death worldwide due to its late-stage detection. Lung cancer screening, including low-dose computed tomography (low-dose CT), provides an initial clinical solution. Nevertheless, further innovations and refinements would help to alleviate remaining limitations. The non-invasive, gentle, and fast nature of breath analysis (BA) makes this technology highly attractive to supplement low-dose CT for an improved screening algorithm. However, BA has not taken hold in everyday clinical practice. One reason might be the heterogeneity and variety of BA methods. This scoping review is a comprehensive summary of study designs, breath analytical methods, and suggested biomarkers in lung cancer. Furthermore, this synthesis provides a framework with core outcomes for future studies in lung cancer BA. This work supports future research for evidence synthesis, meta-analysis, and translation into clinical routine workflows., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MK is cofounder of Deep Breath Intelligence AG (Switzerland), which develops breath-based diagnostic tools. FS is consultants for Deep Breath Intelligence AG (Switzerland). All authors submitted the ICMJE disclosure form., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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 ., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)