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Objectives: To assess the association between socioeconomic status (SES) and self-reported adherence to preventive measures in Switzerland during the COVID-19 pandemic., Methods: 4,299 participants from a digital cohort were followed between September 2020 and November 2021. Baseline equivalised disposable income and education were used as SES proxies. Adherence was assessed over time. We investigated the association between SES and adherence using multivariable mixed logistic regression, stratifying by age (below/above 65 years) and two periods (before/after June 2021, to account for changes in vaccine coverage and epidemiological situation)., Results: Adherence was high across all SES strata before June 2021. After, participants with higher equivalised disposable income were less likely to adhere to preventive measures compared to participants in the first (low) quartile [second (Adj.OR, 95% CI) (0.56, 0.37-0.85), third (0.38, 0.23-0.64), fourth (0.60, 0.36-0.98)]. We observed similar results for education., Conclusion: No differences by SES were found during the period with high SARS-CoV-2 incidence rates and stringent measures. Following the broad availability of vaccines, lower incidence, and eased measures, differences by SES started to emerge. Our study highlights the need for contextual interpretation when assessing SES impact on adherence to preventive measures., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Tancredi, van der Linden, Chiolero, Cullati, Imboden, Probst-Hensch, Keidel, Witzig, Dratva, Michel, Harju, Frank, Lorthe, Baysson, Stringhini, Kahlert, Bardoczi, Haller, Chocano-Bedoya, Rodondi, Amati, Albanese, Corna, Crivelli, Kaufmann, Frei and von Wyl.)

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.)

Previous mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Our study aims to evaluate developments in vaccine uptake and digital proximity tracing app use in a localized context of the SARS-CoV-2 pandemic. Methods: We report findings from two population-based longitudinal cohorts in Switzerland from January to December 2021. Failure time analyses and Cox proportional hazards regression models were conducted to assess vaccine uptake and digital proximity tracing app (SwissCovid) uninstalling outcomes. Results: We observed a dichotomy of individuals who did not use the SwissCovid app and did not get vaccinated, and who used the SwissCovid app and got vaccinated during the study period. Increased vaccine uptake was observed with SwissCovid app use (aHR, 1.51; 95% CI: 1.40-1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62-1.99 [CSM]) compared to SwissCovid app non-use. Decreased SwissCovid uninstallation risk was observed for participants who got vaccinated (aHR, 0.55; 95% CI: 0.38-0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27-0.78 [CSM]) compared to participants who did not get vaccinated. Conclusion: In evolving epidemic contexts, these findings underscore the need for communication strategies as well as flexible digital proximity tracing app adjustments that accommodate different preventive measures and their anticipated interactions., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Daniore, Moser, Höglinger, Probst Hensch, Imboden, Vermes, Keidel, Bochud, Ortega Herrero, Baggio, Chocano-Bedoya, Rodondi, Tancredi, Wagner, Cullati, Stringhini, Gonseth Nusslé, Veys-Takeuchi, Zuppinger, Harju, Michel, Frank, Kahlert, Albanese, Crivelli, Levati, Amati, Kaufmann, Geigges, Ballouz, Frei, Fehr and von Wyl.)

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.)

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.)

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

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).)

Background: During the 2020/2021 winter, the labour market was under the impact of the COVID-19 pandemic. Changes in socioeconomic resources during this period could have influenced individual mental health. This association may have been mitigated or exacerbated by subjective risk perceptions, such as perceived risk of getting infected with SARS-CoV-2 or perception of the national economic situation. Therefore, we aimed to determine if changes in financial resources and employment situation during and after the second COVID-19 wave were prospectively associated with depression, anxiety and stress, and whether perceptions of the national economic situation and of the risk of getting infected modified this association., Methods: One thousand seven hundred fifty nine participants from a nation-wide population-based eCohort in Switzerland were followed between November 2020 and September 2021. Financial resources and employment status were assessed twice (Nov2020-Mar2021, May-Jul 2021). Mental health was assessed after the second measurement of financial resources and employment status, using the Depression, Anxiety and Stress Scale (DASS-21). We modelled DASS-21 scores with linear regression, adjusting for demographics, health status, social relationships and changes in workload, and tested interactions with subjective risk perceptions., Results: We observed scores above thresholds for normal levels for 16% (95%CI = 15-18) of participants for depression, 8% (95%CI = 7-10) for anxiety, and 10% (95%CI = 9-12) for stress. Compared to continuously comfortable or sufficient financial resources, continuously precarious or insufficient resources were associated with worse scores for all outcomes. Increased financial resources were associated with higher anxiety. In the working-age group, shifting from full to part-time employment was associated with higher stress and anxiety. Perceiving the Swiss economic situation as worrisome was associated with higher anxiety in participants who lost financial resources or had continuously precarious or insufficient resources., Conclusion: This study confirms the association of economic stressors and mental health during the COVID-19 pandemic and highlights the exacerbating role of subjective risk perception on this association., (© 2023. The Author(s).)

Background: Informal and formal volunteering engagement is a proxy for social integration and may have beneficial effects for physical and mental well-being in persons with multiple sclerosis (pwMS). As literature on the topic among the pwMS is lacking, this study aimed to determine frequency and type of volunteering performed by pwMS and to identify factors associated with volunteering., Methods: Cross-sectional, self-reported data of 615 pwMS participating in the Swiss Multiple Sclerosis Registry were analyzed using descriptive statistics to determine frequency and type of volunteering engagement. Univariable and multivariable generalized linear models with binomial distribution and log link function were used to identify factors associated with volunteering. Age, sex, employment status and gait disability were added to the multivariable model as fixed confounders. Sociodemographic, health-, work- and daily activity-related factors were included in the analysis., Results: About one third (29.4%) of participants reported engagement in volunteering activities, most often through charities (16.02%) and cultural organizations (14.36%). In the multivariable model, participants who had a university degree were more likely to volunteer than those with lower level of education (RR = 1.48 95% CI [1.14; 1.91]). The ability to pursue daily activities (as measured by the EQ-5D subscale) was strongly associated with participation in volunteering among pwMS. Compared with pwMS who had no or only slight limitations in daily activities, those with severe problems were markedly less likely to engage in volunteering (RR = 0.41, 95% CI [0.21; 0.80]) . Finally, pwMS who reported caring for and supporting their family (i.e., being a homemaker) were more likely to engage in volunteering activities than those who did not (RR = 1.52, 95% CI [1.15; 2.01])., Conclusion: Nearly one in three pwMS engaged in diverse volunteering activities. Having a university degree, being less limited in daily activities and being a homemaker increased the probability of pursuing volunteering activities. Contingent on individual-level motivations, resources or physical abilities, pwMS who experience challenges in performing daily activities or social barriers should be made aware of barrier-free offers of socially inclusive and volunteering activities, often provided by the national MS societies and health leagues., 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. The employer of Chiara Zecca receives support for advisor activities, speaking or grants from Celgene, Genzyme, Lilly, Merck, Novartis, Roche, and grants from Abbvie, Almirall, Biogen Idec, Celgene, Genzyme, Lilly, Merck, Novartis, Roche, Teva Pharma. Pasquale Calabrese has received honoraria for speaking at scientific meetings, serving at scientific advisory boards and consulting activities from Abbvie, Actelion, Almirall, Bayer-Schering, Biogen, EISAI, Lundbeck, Merck Serono, Novartis, Sanofi-Aventis and Teva. He also receives research grants from the Swiss Multiple Sclerosis Society (SMSG), and the Swiss National Research Foundation. Mathias Mettler, Urban Schwegler, Chloé Sieber, Vladeta Ajdacic-Gross, Stephanie Rodgers, Christina Haag, Susanne Kägi, Irene Rapold and Viktor von Wyl declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) impacts education, future career pathways and working capability and therefore may negatively impact the financial situation of persons with MS (pwMS) in Switzerland. We therefore investigated the financial situation and its influencing sociodemographic and disease-specific factors of pwMS compared to the general Swiss population with focus on material deprivation (MD)., Methods: Data on the financial situation of pwMS were collected via a specific questionnaire added to the regular, semi-annual follow-up assessments of the Swiss Multiple Sclerosis Registry. Questions were taken in an unmodified format from the standardized "Statistics on Income and Living Conditions" (SILC) questionnaire 2019 of the Federal Statistical Office of Switzerland which evaluates the financial situation of the general Swiss population, enabling a direct comparison of pwMS with the general Swiss population., Results: PwMS were 1.5 times more frequently affected by MD than the general Swiss population (6.3% of pwMS versus 4.2% of the general Swiss population) which was confirmed in a multivariable logistic regression analysis of pooled SILC and Swiss Multiple Sclerosis Registry (SMSR) data. High symptom burden, having only mandatory schooling, well as having a pending disability insurance application (as opposed to no application or receiving benefits) were associated with a higher odds of MD whereas higher education, older age, having a Swiss citizenship, living with a spouse or a partner or being currently employed were independently associated with a lower odds of MD., Conclusion: MS has a negative impact on the financial situation and is associated with MD. PwMS with a high symptom burden at the transition from work force to receiving disability benefits appeared to be vulnerable for MD. Higher education, older age, having a Swiss citizenship, living with a spouse or a partner or being currently employed were independently associated with a lower odds of MD., Competing Interests: Declaration of Competing Interest Kamm CP 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 (SMSG). Sanak L has no disclosures to report. Von Wyl V has no disclosures to report. Chan A has received speakers’/board honoraria from Actelion (Janssen/J&J), Almirall, Bayer, Biogen, Celgene (BMS), Genzyme, Merck KGaA (Darmstadt, Germany), Novartis, Roche, and Teva, all for hospital research funds. He received research support from Biogen, Genzyme, and UCB, the European Union, and the Swiss National Foundation. He serves as associate editor of the European Journal of Neurology, on the editorial board for Clinical and Translational Neuroscience and as topic editor for the Journal of International Medical Research. Stanikic M reports employment by Roche branch in Serbia, Roche d.o.o. from February 2019 to February 2020. Zina-Mary Manjaly has no disclosures to report. Zecca C is recipient of a grant for senior reseachers provided by AFRI (Area Formazione accademica, Ricerca e Innovazione), EOC. Ente Ospedaliero Cantonale (employer) received compensation for C.Z.’s speaking activities, consulting fees, or research grants from Almirall, Biogen Idec, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sanofi, Teva Pharma, Roche. Calabrese P. has received speakers’/board honoraria from Almirall, Biogen, Celgene (BMS), Genzyme, Novartis, Roche, Schwabe and Teva., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

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

The aim of our study was to investigate whether self-reported feeling of loneliness (FoL) and COVID-19-specific health anxiety were associated with the presence of depressive symptoms during the first coronavirus disease 2019 (COVID-19) wave. Questionnaires of 603 persons of the Swiss Multiple Sclerosis Registry (SMSR) were cross-sectionally analyzed using descriptive and multivariable regression methods. The survey response rate was 63.9%. Depressive symptoms were assessed by the Beck Depression Inventory-Fast Screen (BDI-FS). COVID-19-specific health anxiety and FoL were measured using two 5-item Likert scaled pertinent questions. High scoring FoL (2.52, 95% confidence interval (CI) (2.06-2.98)) and/or COVID-19 specific health anxiety (1.36, 95% CI (0.87-1.85)) were significantly associated with depressive symptoms. Further stratification analysis showed that the impact of FoL on depressive symptoms affected all age groups. However, it was more pronounced in younger PwMS, whereas an impact of COVID-19 specific health anxiety on depressive symptoms was particularly observed in middle-aged PwMS. FoL and COVID-19-specific health anxiety were age-dependently associated with depressive symptoms during the first COVID-19 wave in Switzerland. Our findings could guide physicians, health authorities, and self-help groups to better accompany PwMS in times of public health crises., (© 2022. The Author(s).)

Introduction: Musculoskeletal (MSK) pain conditions, a leading cause of global disability, are usually first managed in primary care settings such as medical, physiotherapy, and chiropractic community-based practices. While chiropractors often treat MSK conditions, there is limited real-world evidence on the topic of health service outcomes among patients receiving this type of care. A nationwide Swiss chiropractic practice-based research network (PBRN) and MSK pain patient cohort study will have potential to monitor the epidemiological trends of MSK pain conditions and contribute to healthcare quality improvement. The primary aims of this protocol are to (1) describe the development of an MSK-focused PBRN within the Swiss chiropractic setting, and (2) describe the methodology of the first nested study to be conducted within the PBRN-an observational prospective patient cohort pilot study., Methods and Analysis: This initiative is conceptualised with two distinct phases. Phase I focuses on the development of the Swiss chiropractic PBRN, and will use a cross-sectional design to collect information from chiropractic clinicians nationwide. Phase II will recruit consecutive patients aged 18 years or older with MSK pain from community-based chiropractic practices participating in the PBRN into a prospective chiropractic cohort pilot study. All data collection will occur through electronic surveys offered in the three Swiss official languages (German, French, Italian) and English. Surveys will be provided to patients prior to their initial consultation in clinics, 1 hour after initial consultation, and at 2, 6 and 12 weeks after initial consultation., Ethics and Dissemination: Ethics approval has been obtained from the independent research ethics committee of Canton Zurich (BASEC-Nr: 2021-01479). Informed consent will be obtained electronically from all participants. Findings will be reported to stakeholders after each study phase, presented at local and international conferences, and disseminated through peer-reviewed publications., Study Pre-Registration: Phase I-Swiss chiropractic PBRN (ClinicalTrials.gov identifier: NCT05046249); Phase 2-Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Widespread vaccination uptake has been shown to be crucial in controlling the COVID-19 pandemic and its consequences on healthcare infrastructures. Infection numbers, hospitalisation rates and mortality can be mitigated if large parts of the population are being vaccinated. However, one year after the introduction of COVID-19 vaccines, a substantial share of the Swiss population still refrains from being vaccinated., Objectives: We analysed COVID-19 vaccination uptake during the first 12 months of vaccine availability. We compared vaccination rates of different socioeconomic subgroups (e.g., education, income, migration background) and regions (urban vs rural, language region) and investigated associations between uptake and individual traits such as health literacy, adherence to COVID-19 prevention measures and trust in government or science., Methods: Our analysis was based on self-reported vaccination uptake of a longitudinal online panel of Swiss adults aged 18 to 79 (the "COVID-19 Social Monitor", analysis sample n = 2448). The panel is representative for Switzerland with regard to age, gender, and language regions. Participants have been periodically surveyed about various public health issues from 30 March 2020, to 16 December 2021. We report uptake rates and age-stratified hazard ratios (HRs) by population subgroups without and with additional covariate adjustment using Cox regression survival analysis., Results: Higher uptake rates were found for individuals with more than just compulsory schooling (secondary: unadjusted HR 1.39, 95% confidence interval [CI] 1.10-1.76; tertiary: HR 1.94, 95% CI 1.52-2.47), household income above CHF 4999 (5000-9999: unadj. HR 1.42, 95% CI 1.25-1.61; ≥10,000 HR 1.99, 95% CI 1.72-2.30), those suffering from a chronic condition (unadj. HR 1.38, 95% CI 1.25-1.53), and for individuals with a sufficient or excellent level of health literacy (sufficient: unadj. HR 1.13, 95% CI 0.98-1.29; excellent: HR 1.21, 95% CI 1.10-1.34). We found lower rates for residents of rural regions (unadj. HR 0.79, 95% CI 0.70-0.88), those showing less adherence to COVID-19 prevention measures, and those with less trust in government or science., Conclusions: Vaccination uptake is multifactorial and influenced by sociodemographic status, health literacy, trust in institutions and expected risk of severe COVID-19 illness. Fears of unwanted vaccine effects and doubts regarding vaccine effectiveness appear to drive uptake hesitancy and demand special attention in future vaccination campaigns.

Introduction: Several disease-modifying therapies (DMTs), covering a broad spectrum of mechanisms of action, have been approved by regulatory agencies for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, only little is known about the current real-world treatment situation in Switzerland. Based on data from a diverse population of 668 persons with RRMS from the Swiss Multiple Sclerosis Registry (SMSR), the present study aims to fill this gap with a descriptive, cross-sectional approach., Methods: Data originated from the SMSR baseline questionnaire and follow-up surveys. Data on current health status and life situation in the last 6 months were extracted from the survey distributed throughout 2020 and 2021, while data on disease-modifying therapy (DMT) histories were included from preceding surveys. Initially, data was stratified into three DMT groups according to the current DMT status (NO (No DMT), CONTINUED (DMT started more than 6 months ago), and NEW (DMT started less than 6 months ago)). In a subsequent analysis, the sample was stratified into groups corresponding to the five most frequently prescribed DMTs. Self-reported outcomes including therapy discontinuation or interruption, relapses and side-effects in the last 6 months were analyzed per group. Life and health situation parameters were also determined and analyzed., Results: The study population consisted of 445 (66.6%) individuals belonging to the CONTINUED, 84 (12.6%) to the NEW, and 139 (20.8%) to the NO group. Within the NO group, 24 (17.3%) reported relapses. Furthermore, self-reported relapses (28 (33.3%)), side-effects (39 (46.4%)), and treatment discontinuations or interruptions (30 (35.7%)) occurred more frequently in the NEW compared to the CONTINUED group (37 (8.3%), 125 (28.1%), 8 (1.8%), respectively). The three groups also differed with respect to age, time since diagnosis, number of symptoms, DMT history, and health-related quality of life. The five most frequently prescribed DMTs included fingolimod (33.4%), dimethyl fumarate (25.0%), ocrelizumab (23.6%), natalizumab (10.6%) and teriflunomide (7.5%). The frequency of self-reported relapses ranged from 9.7% to 13.6%. Notable differences were found in the number of self-reported side-effects, ranging from 9.1% with natalizumab to 56.7% with dimethyl fumarate., Discussion: This cross-sectional analysis suggested that the majority of individuals with RRMS in Switzerland continuously receive tolerable DMT. However, groups not receiving DMT or struggling with side-effects or continued disease worsening while on DMT still persist. It is conceivable that the number of self-reported symptoms indicates the need for more detailed clarification of the DMT characteristics and expectations of treatment outcomes. Injectable DMTs no longer play a major role in the treatment of RRMS in Switzerland and a trend toward an early use of potent drugs is emerging., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To describe the rationale, organization, and procedures of the Corona Immunitas Digital Follow-Up (CI-DFU) eCohort and to characterize participants at baseline. Methods: Participants of Corona Immunitas, a population-based nationwide SARS-CoV-2 seroprevalence study in Switzerland, were invited to join the CI-DFU eCohort in 11 study centres. Weekly online questonnaires cover health status changes, prevention measures adherence, and social impacts. Monthly questionnaires cover additional prevention adherence, contact tracing apps use, vaccination and vaccine hesitancy, and socio-economic changes. Results: We report data from the 5 centres that enrolled in the CI-DFU between June and October 2020 (covering Basel City/Land, Fribourg, Neuchâtel, Ticino, Zurich). As of February 2021, 4636 participants were enrolled and 85,693 weekly and 27,817 monthly questionnaires were collected. Design-based oversampling led to overrepresentation of individuals aged 65+ years. People with higher education and income were more likely to enroll and be retained. Conclusion: Broad enrolment and robust retention of participants enables scientifically sound monitoring of pandemic impacts, prevention, and vaccination progress. The CI-DFU eCohort demonstrates proof-of-principle for large-scale, federated eCohort study designs based on jointly agreed principles and transparent governance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Speierer, Chocano-Bedoya, Anker, Schmid, Keidel, Vermes, Imboden, Levati, Franscella, Corna, Amati, Harju, Luedi, Michel, Veys-Takeuchi, Zuppinger, Nusslé, D’Acremont, Tall, Salberg, Baysson, Lorthe, Pennacchio, Frei, Kaufmann, Geigges, West, Schwab, Cullati, Chiolero, Kahlert, Stringhini, Vollrath, Probst-Hensch, Rodondi, Puhan and von Wyl.)

Background: Switzerland has a liberal implementation of Coronavirus mitigation measures compared to other European countries. Since March 2020, measures have been evolving and include a mixture of central and federalistic mitigation strategies across three culturally diverse language regions. The present study investigates a hypothesised heterogeneity in health, social behavior and adherence to mitigation measures across the language regions by studying pre-specified interaction effects. Our findings aim to support the communication of regionally targeted mitigation strategies and to provide evidence to address longterm population-health consequences of the pandemic by accounting for different pandemic contexts and cultural aspects., Methods: We use data from from the COVID-19 Social Monitor, a longitudinal population-based online survey. We define five mitigation periods between March 2020 and May 2021. We use unadjusted and adjusted logistic regression models to investigate a hypothesized interaction effect between mitigation periods and language regions on selected study outcomes covering the domains of general health and quality of life, mental health, loneliness/isolation, physical activity, health care use and adherence to mitigation measures., Results: We analyze 2,163 (64%) participants from the German/Romansh-speaking part of Switzerland, 713 (21%) from the French-speaking part and 505 (15%) from the Italian-speaking part. We found evidence for an interaction effect between mitigation periods and language regions for adherence to mitigation measures, but not for other study outcomes (social behavior, health). The presence of poor quality of life, lack of energy, no physical activity, health care use, and the adherence to mitigation measures changed similarly over mitigation periods in all language regions., Discussion: As the pandemic unfolded in Switzerland, also health and social behavior changed between March 2020 to May 2021. Changes in adherence to mitigation measures differ between language regions and reflect the COVID-19 incidence patterns in the investigated mitigation periods, with higher adherence in regions with previously higher incidence. Targeted communcation of mitigation measures and policy making should include cultural, geographical and socioeconomic aspects to address yet unknown long-term population health consequences caused by the pandemic., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We aimed to evaluate the effectiveness of the SwissCovid digital proximity tracing (DPT) app in notifying exposed individuals and prompting them to quarantine earlier compared to individuals notified only by manual contact tracing (MCT). Methods: A population-based sample of cases and close contacts from the Zurich SARS-CoV-2 Cohort was surveyed regarding SwissCovid app use and SARS-CoV-2 exposure. We descriptively analyzed app adherence and effectiveness, and evaluated its effects on the time between exposure and quarantine among contacts using stratified multivariable time-to-event analyses. Results: We included 393 SARS-CoV-2 infected cases and 261 close contacts. 62% of cases reported using SwissCovid and among those, 88% received and uploaded a notification code. 71% of close contacts were app users, of which 38% received a warning. Non-household contacts notified by SwissCovid started quarantine 1 day earlier and were more likely to quarantine earlier than those not warned by the app (HR 1.53, 95% CI 1.15-2.03). Conclusion: These findings provide evidence that DPT may reach exposed contacts faster than MCT, with earlier quarantine and potential interruption of SARS-CoV-2 transmission chains., Competing Interests: The Swiss School of Public Health (SSPH+) coordinates and performs fundraising for the overarching Corona Immunitas research program, of which the Zurich SARS-CoV-2 Cohort study is part. 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 © 2021 Ballouz, Menges, Aschmann, Domenghino, Fehr, Puhan and von Wyl.)

Objectives: When research evidence is lacking, patient and provider preferences, expected to vary geographically, might have a stronger role in clinical decisions. We investigated whether the strength or the direction of recommendation is associated with the degree of geographic variation in utilisation., Design: In this cross-sectional study, we selected 24 services following a comprehensive approach. The strength and direction of recommendations were assessed in duplicate. Multilevel models were used to adjust for demographic and clinical characteristics and estimate unwarranted variation., Setting: Observational study of claims to mandatory health insurance in Switzerland in 2014., Participants: Enrolees eligible for the 24 healthcare services., Primary Outcome Measures: The variances of regional random effects, also expressed as median odds ratios (MOR). Services grouped by strength and direction of recommendations were compared with Welch's t-test., Results: The sizes of the eligible populations ranged from 1992 to 409 960 patients. MOR ranged between 1.13 for aspirin in secondary prevention of myocardial infarction to 1.68 for minor surgical procedures performed in inpatient instead of outpatient settings. Services with weak recommendations had a negligibly higher variance and MOR (difference in means (95% CI) 0.03 (-0.06 to 0.11) and 0.05 (-0.11 to 0.21), respectively) compared with strong recommendations. Services with negative recommendations had a slightly higher variance and MOR (difference in means (95% CI) 0.07 (-0.03 to 0.18) and 0.14 (-0.06 to 0.34), respectively) compared with positive recommendations., Conclusions: In this exploratory study, the geographical variation in the utilisation of services associated with strong vs weak and negative vs positive recommendations was not substantially different, although the difference was somewhat larger for negative vs positive recommendations. The relationships between the strength or direction of recommendations and the variation may be indirect or modified by other characteristics of services. As initiatives discouraging low-value care are gaining attention worldwide, these findings may inform future research in this area., Competing Interests: Competing interests: MS declares a grant from Helsana Insurance Group, outside the submitted work. Helsana Group provided support in the form of salaries for authors BB, EB and CB, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To compare and characterize major depressive disorder (MDD) subtypes (i.e., pure atypical, pure melancholic and mixed atypical-melancholic) and depression symptoms in persons with multiple sclerosis (PwMS) with persons without MS (Pw/oMS) fulfilling the DSM-5 criteria for a past 12-month MDD., Methods: MDD in PwMS (n = 92) from the Swiss Multiple Sclerosis Registry was compared with Pw/oMS (n = 277) from a Swiss community-based study. Epidemiological MDD diagnoses were based on the Mini-SPIKE (shortened form of the Structured Psychopathological Interview and Rating of the Social Consequences for Epidemiology). Logistic and multinomial regression analyses (adjusted for sex, age, civil status, depression and severity) were computed for comparisons and characterization. Latent class analysis (LCA) was conducted to empirically identify depression subtypes in PwMS., Results: PwMS had a higher risk for the mixed atypical-melancholic MDD subtype (OR = 2.22, 95% CI = 1.03-4.80) compared to Pw/oMS. MDD in PwMS was specifically characterized by a higher risk of the two somatic atypical depression symptoms 'weight gain' (OR = 6.91, 95% CI = 2.20-21.70) and 'leaden paralysis' (OR = 3.03, 95% CI = 1.35-6.82) and the symptom 'irritable/angry' (OR = 3.18, 95% CI = 1.08-9.39)., Conclusions: MDD in PwMS was characterized by a higher risk for specific somatic atypical depression symptoms and the mixed atypical-melancholic MDD subtype. The pure atypical MDD subtype, however, did not differentiate between PwMS and Pw/oMS. Given the high phenomenological overlap with MS symptoms, the mixed atypical-melancholic MDD subtype represents a particular diagnostic challenge., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Digital contact tracing (DCT) apps have been released in several countries to help interrupt SARS-CoV-2 transmission chains. However, the effect of DCT on pandemic mitigation remains to be demonstrated., Objective: To estimate key populations and performance indicators along the exposure notification cascade of the SwissCovid DCT app in a clearly defined regional and temporal context., Design, Setting, and Participants: This comparative effectiveness study was based on a simulation informed by measured data from issued quarantine recommendations and positive SARS-CoV-2 test results after DCT exposure notifications in the canton of Zurich. A stochastic model was developed to re-create the DCT notification cascade for Zurich. Population sizes at each cascade step were estimated using triangulation based on publicly available administrative and observational research data for the study duration from September 1 to October 31, 2020. The resultant estimates were checked for internal consistency and consistency with upstream or downstream estimates in the cascade. Stochastic sampling from data-informed parameter distributions was performed to explore the robustness of results. Subsequently, key performance indicators were evaluated to assess the potential contribution of DCT compared with manual contact tracing., Main Outcomes and Measures: Receiving a voluntary quarantine recommendation and/or a positive SARS-CoV-2 test result after exposure notification., Results: In September 2020, 537 app users received a positive SARS-CoV-2 test result in Zurich, 324 of whom received and entered an upload authorization code. This code triggered an app notification for an estimated 1374 (95% simulation interval [SI], 932-2586) proximity contacts and led to 722 information hotline calls, with an estimated 170 callers (95% SI, 154-186) receiving a quarantine recommendation. An estimated 939 (95% SI, 720-1127) notified app users underwent testing for SARS-CoV-2, of whom 30 (95% SI, 23-36) had positive results after an app notification. Key indicator evaluations revealed that the DCT app triggered quarantine recommendations for the equivalent of 5% of all exposed contacts placed in quarantine by manual contact tracing. For every 10.9 (95% SI, 7.6-15.6) upload authorization codes entered in the app, 1 contact had positive test results for SARS-CoV-2 after app notification. Longitudinal indicator analyses demonstrated bottlenecks in the notification cascade, because capacity limits were reached owing to an increased incidence of SARS-CoV-2 infection in October 2020., Conclusions and Relevance: In this simulation study of the notification cascade of the SwissCovid DCT app, receipt of exposure notifications was associated with quarantine recommendations and identification of SARS-CoV-2-positive cases. These findings in notified proximity contacts reflect important intermediary steps toward transmission prevention.

Background: Several countries have released digital proximity tracing (DPT) apps to complement manual contact tracing for combatting the SARS-CoV-2 pandemic. DPT aims to notify app users about proximity exposures to persons infected with SARS-CoV-2 so that they can self-quarantine. The success of DPT apps depends on user acceptance and the embedding of DPT into the pandemic mitigation strategy., Objective: By searching for media articles published during the first 3 months after DPT launch, the implementation of DPT in Switzerland was evaluated to inform similar undertakings in other countries. The second aim of the study was to create a link between reported DPT implementation challenges and normalization process theory for planning and optimizing complex digital health interventions, which can provide useful guidance for decision-making in DPT design and implementation., Methods: A Swiss media database was searched for articles on the Swiss DPT app (SwissCovid) published in German or French between July 4 and October 3, 2020. In a structured process, topics were extracted and clustered manually from articles that were deemed pertinent. Extracted topics were mapped to four NPT constructs, which reflected the flow of intervention development from planning, stakeholder onboarding, and execution to critical appraisal. Coherence constructs describe sense-making by stakeholders, cognitive participation constructs reflect participants' efforts to create engagement with the intervention, collective actions refer to intervention execution and joint stakeholder efforts to make the intervention work, and reflexive monitoring refers to collective risk-benefit appraisals to create improvements., Results: Out of 94 articles deemed pertinent and selected for closer inspection, 38 provided unique information on implementation challenges. Five challenge areas were identified: communication challenges, challenges for DPT to interface with other processes, fear of resource competition with established pandemic mitigation measures, unclear DPT effectiveness, and obstacles to greater user coverage and compliance. Specifically, several articles mentioned unclear DPT benefits to affect commitment and to raise fears among different health system actors regarding resource competition. Moreover, media reports indicated process interface challenges such as delays or unclear responsibilities in the notification cascade, as well as misunderstandings and unmet communication needs from health system actors. Finally, reports suggested misaligned incentives, not only for app usage by the public but also for process engagement by other actors in the app notification cascade. NPT provided a well-fitting framework to contextualize the different DPT implementation challenges and to highlight improvement strategies, namely a better alignment of stakeholder incentives, or stakeholder-specific communication to address their concerns about DPT., Conclusions: Early experiences from one of the first adopters of DPT indicate that nontechnical implementation challenges may affect the effectiveness of DPT. The NPT analysis provides a novel perspective on DPT implementation and stresses the need for stakeholder inclusion in development and operationalization., (©Viktor von Wyl. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 26.02.2021.)

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

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

In the wake of the pandemic of coronavirus disease 2019 (COVID-19), contact tracing has become a key element of strategies to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given the rapid and intense spread of SARS-CoV-2, digital contact tracing has emerged as a potential complementary tool to support containment and mitigation efforts. Early modelling studies highlighted the potential of digital contact tracing to break transmission chains, and Google and Apple subsequently developed the Exposure Notification (EN) framework, making it available to the vast majority of smartphones. A growing number of governments have launched or announced EN-based contact tracing apps, but their effectiveness remains unknown. Here, we report early findings of the digital contact tracing app deployment in Switzerland. We demonstrate proof-of-principle that digital contact tracing reaches exposed contacts, who then test positive for SARS-CoV-2. This indicates that digital contact tracing is an effective complementary tool for controlling the spread of SARS-CoV-2. Continued technical improvement and international compatibility can further increase the efficacy, particularly also across country borders.

Aims of the Study: During the transitional phase between the two pandemic waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infection rates were temporarily rising among younger persons only. However, following a temporal delay infections started to expand to older age groups. A comprehensive understanding of such transmission dynamics will be key for managing the pandemic in the time to come and to anticipate future developments. The present study thus extends the scope of previous SARS-CoV-2-related research in Switzerland by contributing to deeper insight into the potential impact of “social mixing” of different age groups on the spread of SARS-CoV-2 infections., Methods: The present study examined persons aged 65 years and older with respect to possible SARS-CoV-2 exposure risks using longitudinal panel data from the Swiss COVID-19 Social Monitor. The study used data from two assessments (survey “May” and survey “August”). Survey “May” took place shortly after the release of the lockdown in Switzerland. Survey “August” was conducted in mid-August. To identify at-risk elderly persons, we conducted a combined factor/k-means clustering analysis of the survey data assessed in August in order to examine different patterns of adherence to recommended preventive measures., Results: In summary, 270 (survey “May”) and 256 (survey “August”) persons aged 65 years and older were analysed for the present study. Adherence to established preventive measures was similar across the two surveys, whereas adherence pertaining to social contacts decreased substantially from survey “May” to survey “August”. The combined factor/k-means clustering analysis to identify at-risk elderly individuals yielded four distinct groups with regard to different patterns of adherence to recommended preventive measures: a larger group of individuals with many social contacts but high self-reported adherence to preventive measures (n = 86); a small group with many social contacts and overall lower adherence (n = 26); a group with comparatively few contacts and few social activities (n = 66); and a group which differed from the latter through fewer contacts but more social activities (n = 78). Sociodemographic characteristics and risk perception with regard to SARS-CoV-2 infections among the four groups did not differ in a relevant way across the four groups., Conclusions: Although many elderly persons continued to follow the recommended preventive measures during the transitional phase between the two pandemic waves, social mixing with younger persons constitutes a way for transmission of infections across age groups. Pandemic containment among all age groups thus remains essential to protect vulnerable populations, including the elderly.

Background: Regional variation in healthcare utilization could reflect unequal access to care, which may lead to detrimental consequences to quality of care and costs. The aims of this study were to a) describe the degree of regional variation in utilization of 24 diverse healthcare services in eligible populations in Switzerland, and b) identify potential drivers, especially health insurance-related factors, and explore the consistency of their effects across the services., Methods: We conducted a cross-sectional study using health insurance claims data for the year of 2014. The studied 24 healthcare services were predominantly outpatient services, ranging from screening to secondary prevention. For each service, a target population was identified based on applicable clinical recommendations, and outcome variable was the use of the service. Possible influencing factors included patients' socio-demographics, health insurance-related and clinical characteristics. For each service, we performed a comprehensive methodological approach including small area variation analysis, spatial autocorrelation analysis, and multilevel multivariable modelling using 106 mobilité spaciale regions as the higher level. We further calculated the median odds ratio in model residuals to assess the unexplained regional variation., Results: Unadjusted utilization rates varied considerably across the 24 healthcare services, ranging from 3.5% (osteoporosis screening) to 76.1% (recommended thyroid disease screening sequence). The effects of health insurance-related characteristics were mostly consistent. A higher annual deductible level was mostly associated with lower utilization. Supplementary insurance, supplementary hospital insurance and having chosen a managed care model were associated with higher utilization of most services. Managed care models showed a tendency towards more recommended care. After adjusting for multiple influencing factors, the unexplained regional variation was generally small across the 24 services, with all MORs below 1.5., Conclusions: The observed utilization rates seemed suboptimal for many of the selected services. For all of them, the unexplained regional variation was relatively small. Our findings confirmed the importance and consistency of effects of health insurance-related factors, indicating that healthcare utilization might be further optimized through adjustment of insurance scheme designs. Our comprehensive approach aids in the identification of regional variation and influencing factors of healthcare services use in Switzerland as well as comparable settings worldwide.

Background: Multiple sclerosis (MS) notably affects adults of working age. For persons with MS (PwMS), being employed enhances their quality of life and it may be regarded as an indicator of overall functioning. Thus, ensuring work participation in PwMS is of general public health interest., Objective: To examine relevant socio-demographic, MS-, health- and work-related factors, including psychosocial working conditions, associated with currently working PwMS in Switzerland and their expected work retention., Methods: Using cross-sectional data of PwMS in the Swiss MS Registry (n = 541, median age = 48 [IQR 40;55]), multivariable logistic regression models were computed. First, currently working PwMS were characterised in comparison with those not currently working. Second, expected work retention, operationalized as subjective judgement "likely to work in the same job in 2 years", was examined within the group of currently working PwMS., Results: The factors age (OR 0.96, 95% CI 0.92-0.99), sex (OR 0.28, 95% CI 0.13-0.60), highest achieved job position (OR 1.21, 95% CI 1.01-1.46), health-related quality of life (HRQoL) (OR 1.02, 95% CI 1.01-1.04) and the number of MS symptoms (OR 0.90, 95% CI 0.82-0.98) were associated with currently working PwMS. Moreover, HRQoL (OR 1.07, 95% CI 1.04-1.10) and psychosocial working conditions, such as job resources (e.g. autonomy, control or social support) (OR 2.83, 95% CI 1.50-5.33) and job demands (e.g. workload, time pressure) (OR 0.41, 95% CI 0.18-0.90) were important factors for expected work retention among this group., Conclusions: Resourceful psychosocial working conditions are crucial for PwMS to maintain employment. Employers could contribute to work retention among PwMS by creating a work environment with resourceful psychosocial working conditions and providing, for instance, social support.

Background: Observational studies of influenza vaccination are criticized as flawed due to unmeasured confounding. The goal of this cohort study was to explore the value and role of secondary claims data to inform the effectiveness of influenza vaccination, while systematically trying to reduce potential bias., Methods: We iteratively reviewed the components of the PICO approach to refine study design. We analyzed Swiss mandatory health insurance claims of adult patients with chronic diseases, for whom influenza vaccination was recommended in 2014. Analyzed outcomes were all-cause mortality, hospitalization with a respiratory infection or its potential complication, and all-cause mortality after such hospitalization, adjusting for clinical and health care use variables. Cox and multi-state models were applied for time-to-event analysis., Results: Of 343,505 included persons, 22.4% were vaccinated. Vaccinated patients were on average older, had more morbidities, higher health care expenditures, and had been more frequently hospitalized. In non-adjusted models, vaccination was associated with increased risk of events. Adding covariates decreased the hazard ratio (HR) both for mortality and hospitalizations. In the full model, the HR [95% confidence interval] for mortality during season was 0.82 [0.77-0.88], and closer to null effect after season. In contrast, HR for hospitalizations was increased during season to 1.28 [1.15-1.42], with estimates closer to null effect after season. HR in multi-state models were similar to those in the single-outcome models, with HR of mortality after hospitalization negative both during and after season., Conclusion: In patients with chronic diseases, influenza vaccination was associated with more frequent specific hospitalizations, but decreased risk of mortality overall and after such hospitalization. Our approach of iteratively considering PICO elements helped to consider various sources of bias in the study sequentially. The selection of appropriate, specific outcomes makes the link between intervention and outcome more plausible and can reduce the impact of confounding., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MS declares a grant from Helsana Insurance Group, outside the submitted work. Helsana Group provided support in the form of salaries for authors BB, EB and CB, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Variation in utilization of healthcare services is influenced by patient, provider and healthcare system characteristics. It could also be related to the evidence supporting their use, as reflected in the availability and strength of recommendations in clinical guidelines. In this study, we analyzed the geographic variation of colorectal, breast and prostate cancer screening utilization in Switzerland and the influence of available guidelines and different modifiers of access. Colonoscopy, mammography and prostate specific antigen (PSA) testing use in eligible population in 2014 was assessed with administrative claims data. We ran a multilevel multivariable logistic regression model and calculated Moran's I and regional level median odds ratio (MOR) statistics to explore residual geographic variation. In total, an estimated 8.1% of eligible persons received colonoscopy, 22.3% mammography and 31.3% PSA testing. Low deductibles, supplementary health insurance and enrollment in a managed care plan were associated with higher screening utilization. Cantonal breast cancer screening programs were also associated with higher utilization. Spatial clustering was observed in the raw regional utilization of all services, but only for prostate cancer screening in regional residuals of the multilevel model. MOR was highest for prostate cancer screening (1.24) and lowest for colorectal cancer screening (1.16). The reasons for the variation of the prostate cancer screening utilization, not recommended routinely without explicit shared decision-making, could be further investigated by adding provider characteristics and patient preference information. This first cross-comparison of different cancer screening patterns indicates that the strength of recommendations, mediated by specific health policies facilitating screening, may indeed contribute to variation., Competing Interests: MS declares a grant from Helsana Insurance Group, outside the submitted work. CB, EB and BB are employed by the Helsana Group. Helsana Group had no role in the planning, conducting or submission of this manuscript. These authors declare no conflict of interest. Helsana Group shall have no liability to any third party in respect to the contents of this article. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. The remaining authors have declared that no competing interests exist.

Background: Diagnosing multiple sclerosis (MS) early is crucial to avoid future disability. However, potentially preventable delays in the diagnostic cascade from contact with a physician to definite diagnosis still occur and their causes are still unclear., Objective: To identify the possible causes of delays in the diagnostic process., Methods: We analyzed the data of the Swiss MS Registry. With logistic regression, we modeled the time from the first contact to the first consultation (contact-to-evaluation time, ⩽1 month/>1 month) and the evaluation-to-diagnosis time (⩽6 months/>6 months). Potential factors were health system characteristics, sociodemographic variables, first symptoms, and MS type., Results: We included 522 participants. Mostly, general practitioners (67%) were contacted first, without delaying the diagnosis. In contrast, first symptoms and MS type were the major contributors to delays: gait problems were associated with longer contact-to-evaluation times, depression as a concomitant symptom with longer evaluation-to-diagnosis times, and having primary progressive MS prolonged both phases. In addition, living in mountainous areas was associated with longer contact-to-evaluation times, whereas diagnosis after 2000 was associated with faster diagnoses., Conclusion: For a quicker diagnosis, awareness of MS as a differential diagnosis of gait disorders and the co-occurrence of depression at onset should be raised, and these symptoms should be attentively followed.

Introduction: Four strongly recommended diabetes management measures are biannual glycated hemoglobin (HbA1c) testing, annual eye examination, kidney function examination, and low-density lipoprotein (LDL) testing in patients below 75 years. We aimed to describe regional variation in the utilization of the four measures across small regions in Switzerland and to explore potential influencing factors., Research Design and Methods: We conducted a cross-sectional study of adult patients with drug-treated diabetes in 2014 using claims data. Four binary outcomes represented adherence to the recommendations. Possible influencing factors included sociodemographics, health insurance preferences, and clinical characteristics. We performed multilevel modeling with Medstat regions as the higher level. We calculated the median odds ratio (MOR) and checked spatial autocorrelation in region level residuals using Moran's I statistic. When significant, we further conducted spatial multilevel modeling., Results: Of 49 198 patients with diabetes (33 957 below 75 years), 69.6% had biannual HbA1c testing, 44.3% each had annual eye examination and kidney function examination, and 55.5% of the patients below 75 years had annual LDL testing. The effects of health insurance preferences were substantial and consistent. Having any supplementary insurance (ORs across measures were between 1.08 and 1.28), having supplementary hospital care insurance (1.08-1.30), having chosen a lower deductible level (eg, SFr2500 compared with SFr300: 0.57-0.69), and having chosen a managed care model (1.04-1.17) were positively associated with recommendations adherence. The MORs (1.27-1.33) showed only moderate unexplained variation, and we observed inconsistent spatial patterns of unexplained variation across the four measures., Conclusion: Our findings indicate that the uptake of strongly recommended measures in diabetes management could possibly be optimized by providing further incentives to patients and care providers through insurance scheme design. The absence of marked regional variation implies limited potential for improvement by targeted regional intervention, while provider-specific promotion may be more impactful., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patient satisfaction is predictive of adherence, malpractice litigation and doctor-switching., Objective: To investigate which factors of the first diagnostic consultation (FDC) influence patient satisfaction and which topics persons with multiple sclerosis (PwMS) thought were missing., Methods: Using retrospective patient-reported data of the Swiss Multiple Sclerosis Registry from PwMS with relapsing disease onset, we fitted ordered logistic regression models on satisfaction with FDC, with socio-demographic and FDC features as explanatory factors., Results: 386 PwMS diagnosed after 1995 were included. Good satisfaction with the FDC was associated with a conversation more than 20 min [multivariable odds ratio, 95% confidence interval 3.9 (2.42; 6.27)], covering many topics [1.35 (1.19; 1.54) per additional topic], the presence of a significant others [1.74 (1.03; 2.94) ], and shared decision making [3.39 (1.74; 6.59)]. Not receiving a specific diagnosis was main driver for low satisfaction [0.29 (0.15; 0.55)]. Main missing topics concerned long-term consequences (reported by 6.7%), psychological aspects (6.2%) and how to obtain support and further information (5.2%)., Conclusions: A conversation of more than 20 min covering many MS relevant topics, a clear communication of the diagnosis, the presence of a close relative or significant other, as well as shared decision making enhanced patient satisfaction with the FDC. ClinicalTrials.gov Identifier: NCT02980640.

Objectives: Indicators of guideline adherence are frequently used to examine the appropriateness of healthcare services. Only some potential indicators are actually usable for research with routine administrative claims data, potentially leading to a biased selection of research questions. This study aimed at developing a systematic approach to extract potential indicators from clinical practice guidelines (CPG), evaluate their feasibility for research with claims data and assess how the extracted set reflected different types of healthcare services. Diabetes mellitus (DM), Swiss national guidelines and health insurance claims data were analysed as a model case., Methods: CPG for diabetes patients were retrieved from the Swiss Endocrinology and Diabetes Society website. Recommendation statements involving a specific healthcare intervention for a defined patient population were translated into indicators of guideline adherence. Indicators were classified according to disease stage and healthcare service type. We assessed for all indicators whether they could be analysed with Swiss mandatory health insurance administrative claims data., Results: A total of 93 indicators were derived from 15 CPG, representing all sectors of diabetes care. For 63 indicators, the target population could not be identified using claims data only. For 67 indicators, the intervention could not be identified. Nine (10%) of all indicators were feasible for research with claims data (three addressed gestational diabetes and screening, five screening for complications and one glucose measurement). Some types of healthcare services, eg, management of risk factors, treatment of the disease and secondary prevention, lacked corresponding indicators feasible for research., Conclusions: Our systematic approach could identify a number of indicators of healthcare service utilisation, feasible for DM research with Swiss claims data. Some areas of healthcare were covered less well. The approach could be applied to other diseases and countries, helping to identify the potential bias in the selection of indicators and optimise research., Competing Interests: Competing interests: None declared., (© 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.)

Background: Current guidelines recommend regular neurological MS care in persons diagnosed with MS, but little is known about implementation of this recommendation or potential access barriers. This study examined disease-specific and sociodemographic differences between MS patients in Neurological Care (NeC), General Practitioner Care (GPC), or no Physician Care (NoPC) to identify group differences and characteristics that may suggest care access barriers., Methods: Patient-reported data were analyzed from 1038 Swiss Multiple Sclerosis Registry participants by means of multivariable regression to identify systematic differences across the three care groups. Assessments included comprehensive data on clinical, sociodemographic, and geographic factors., Results: 89% reported being in regular care by a neurologist (56% in private practices, 44% in hospitals), 5% were in GPC, and 6% reported No Physician Care (NoPC). Compared with the NeC group, patients not seeing a neurologist included two subgroups, one consisting of persons with a primary progressive MS (PPMS) and/or an extended MS history. The second subgroup included persons with a recent MS diagnosis within the last 2 years. Within the NeC group, the patients seen in private practices were of older age and more frequently female compared to those at clinics, but no differences were detected with regard to disability status, MS type, or treatment patterns., Conclusions: Access to neurological care is high in Switzerland. Given the emerging paradigm for early treatment and new drugs for progressive MS, regular neurology visits should be promoted among patient groups currently less in neurological care such as persons with PPMS or recently diagnosed., (Copyright © 2018. Published by Elsevier B.V.)

Clinical recommendations discourage routine use of preoperative chest radiography (POCR). However, there remains much uncertainty about its utilization, especially variation across small areas. We aimed to assess the variation of POCR use across small regions, and to explore its influencing factors. Patients undergoing inpatient surgery during 2013 to 2015 were identified from insurance claims data. Possible influencing factors of POCR included socio-demographics, health insurance choices, and clinical characteristics. We performed multilevel modelling with region and hospital as random effects. We calculated 80% interval odds ratios (IOR-80) to describe the effect of hospital type, and median odds ratios (MOR) to assess the degree of higher level variation. Utilization rates of POCR varied from 2.5% to 44.4% across regions. Higher age, intrathoracic pathology, and multi-morbidity were positively associated with the use of POCR. Female gender, choice of high franchise and supplementary hospital insurance showed a negative association. MOR was 1.25 and 1.69 for region and hospital levels, respectively. IOR-80s for hospital type were wide and covered the value of one. We observed substantial variation of POCR utilization across small regions in Switzerland. Even after controlling for multiple factors, variation across small regions and hospitals remained. Underlying mechanisms need to be studied further.

Background: MS symptoms affect many functional domains. Knowing the specific impact of symptoms on health-related quality of life (HRQoL) is vital for successful disease and symptom management in MS. We aimed at investigating how specific MS symptoms contribute to the disease burden in individuals and from a population perspective., Methods: We included 855 Swiss Multiple Sclerosis Registry participants with a relapsing-remitting form (RRMS) or a progressive form (PMS). HRQoL was measured with the EuroQol 5-Dimension EQ-5D-index and EQ-Visual Analogue Scale (EQ-VAS) on 0-100% scales. Their associations with 20 symptoms, socio-demographic and clinical information were explored in median regression models, stratified by RRMS and PMS., Results: We included 611 participants with RRMS and 244 with PMS. In RRMS, gait (-6.5%) and balance problems (-5.1%) had the largest EQ-5D-index reductions, and were also important at the population level (frequencies 45% and 52%). Fatigue, depression, and spasticity (frequencies 74.1%, 31%, 38%) also contributed to the population disease burden. In PMS, spasticity, paralysis, and bowel problems had the largest impact on EQ-5D-index, both at the individual and population levels. The largest impact on EQ-VAS at population level was associated in RRMS with balance problems, depression, dizziness, and spasticity, while in PMS with weakness, pain, and paralysis., Conclusions: While HRQoL at population level is most affected by balance problems, spasticity, and depression in RRMS, the biggest HRQoL losses in PMS are caused by spasticity, paralysis, weakness, and pain. Many symptoms with the largest effects in individuals substantially contribute to the population disease burden., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Exploration of healthcare utilisation patterns in the final life year to assess palliative care potential., Methods: Retrospective cluster analyses (k-means) of anonymised healthcare expenditure (HCE) trajectories, derived from health insurance claims of a representative sample of Swiss decedents who died between 2008 and 2010 (2 age classes: 4818 <66 years, 22 691 elderly)., Results: 3 (<66 years) and 5 (elderly) trajectory groups were identified, whose shapes were dominated by HCE from inpatient care in hospitals and at nursing homes. In each age class, the most expensive group (average cumulative HCE for <66 years: SFr 84 295; elderly: SFr 84 941) also had the largest abundance of cancers (<66 years: 55%; elderly: 32%) and showed signs of continued treatment intensification until shortly before death. Although sizes of these high-cost groups were comparatively small (26% in younger; 6% in elderly), they contributed substantially to the end-of-life HCE in each age class (62% and 18%, respectively).As age increased, these potential target groups for palliative care gained in share among <66-year olds (from 9% in children to 28% in 60-65-year olds), but decreased from 17% (66-70-year olds) to 1% (>90-year olds) among elderly., Conclusions: Cost trajectory clustering is well suited for first-pass population screenings of groups that warrant closer inspection to improve end-of-life healthcare allocation. The Swiss data suggest that many decedents undergo intensive medical treatment until shortly before death. Investigations into the clinical circumstances and motives of patients and physicians may help to guide palliative care., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Outcomes of very preterm infants vary considerably between health care facilities. Our objective was to compare outcome and practices between the Swiss Neonatal Network (SNN) and US members of the Vermont Oxford Network (US-VON)., Methods: Retrospective observational study including all live-born infants with a birth weight between 501 and 1500 g as registered by SNN and US-VON between 2012 and 2014. We performed multivariable and propensity score-matched analyses of neonatal outcome by adjusting for case-mix, race, prenatal care, and unit-level factors, and compared indirectly standardized practices., Results: A total of 123 689 infants were born alive in 696 US-VON units and 2209 infants were born alive in 13 SNN units. Adjusted risk ratios (aRRs) for the composite "death or major morbidity" (aRR: 0.56, 95% confidence interval: 0.51-0.62) and all other outcomes were either comparable or lower in SNN except for mortality, for which aRR was higher (aRR: 1.28, 95% confidence interval: 1.09-1.50). Propensity score matching and restricting the analysis to infants for which we expect no survival bias, because both networks routinely initiate intensive care at birth, revealed comparable aRR. Variations in observed practices between SNN and US-VON were large., Conclusions: The SNN units had a significantly lower risk ratio for death or major morbidity. Despite higher mortality, this difference is independent of survival bias. The higher delivery room mortality reflects the SNN practice to favor primary nonintervention for infants born <24 completed gestational weeks. We propose further research into which practice differences have the strongest beneficial impact., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Mr Adams receives a salary as network coordinator for the Swiss Neonatal Network. Dr Soll receives a salary as president of the Vermont Oxford Network. Dr Edwards receives a salary from the University of Vermont through a position funded by Vermont Oxford Network; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background: Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR., Methods: ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates., Results: One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F., Conclusions: Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.

Background: Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)-naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven., Methods: MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters., Results: Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1-infected patients (8.2% vs 2.5%; P = .004)., Conclusions: Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin-transmission vs sporadic appearance-of these variants determines their impact on ART needs to be further explored.

Background: We hypothesized that polymorphic mutations exist that are associated with the emergence of the multinucleoside resistance mutations (MNR), 69 insertion and Q151M., Methods: The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), ≥2 thymidine analogue mutations (TAM) 1 (n = 400) or ≥2 TAM 2 (n = 249). Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR., Results: The 69 insertion and TAM 1 were strongly associated and occurred in 94.1% (16 of 17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared with 4.4 for ≥2 TAM 1, P Wilcoxon = 0.009). Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. S68G, T165I, and I202V were associated with Q151M instead of TAM 2., Conclusions: Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations.

Background: Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important., Methods: The effect of HIV-1 subtype B and non-B on the time to virological failure while taking combination antiretroviral therapy (cART) was analyzed. Other studies that have addressed this question were limited by the strong correlation between subtype and ethnicity. Our analysis was restricted to white patients from the Swiss HIV Cohort Study who started cART between 1996 and 2009. Cox regression models were performed; adjusted for age, sex, transmission category, first cART, baseline CD4 cell counts, and HIV RNA levels; and stratified for previous mono/dual nucleoside reverse-transcriptase inhibitor treatment., Results: Included in our study were 4729 patients infected with subtype B and 539 with non-B subtypes. The most prevalent non-B subtypes were CRF02&#95;AG (23.8%), A (23.4%), C (12.8%), and CRF01&#95;AE (12.6%). The incidence of virological failure was higher in patients with subtype B (4.3 failures/100 person-years; 95% confidence interval [CI], 4.0-4.5]) compared with non-B (1.8 failures/100 person-years; 95% CI, 1.4-2.4). Cox regression models confirmed that patients infected with non-B subtypes had a lower risk of virological failure than those infected with subtype B (univariable hazard ratio [HR], 0.39 [95% CI, .30-.52; P < .001]; multivariable HR, 0.68 [95% CI, .51-.91; P = .009]). In particular, subtypes A and CRF02&#95;AG revealed improved outcomes (multivariable HR, 0.54 [95% CI, .29-.98] and 0.39 [95% CI, .19-.79], respectively)., Conclusions: Improved virological outcomes among patients infected with non-B subtypes invalidate concerns that these individuals are at a disadvantage because drugs have been designed primarily for subtype B infections.

When applying survival analysis, such as Cox regression, to data from major clinical trials or other studies, often only baseline covariates are used. This is typically the case even if updated covariates are available throughout the observation period, which leaves large amounts of information unused. The main reason for this is that such time-dependent covariates often are internal to the disease process, as they are influenced by treatment, and therefore lead to confounded estimates of the treatment effect. There are, however, methods to exploit such covariate information in a useful way. We study the method of dynamic path analysis applied to data from the Swiss HIV Cohort Study. To adjust for time-dependent confounding between treatment and the outcome 'AIDS or death', we carried out the analysis on a sequence of mimicked randomized trials constructed from the original cohort data. To analyze these trials together, regular dynamic path analysis is extended to a composite analysis of weighted dynamic path models. Results using a simple path model, with one indirect effect mediated through current HIV-1 RNA level, show that most or all of the total effect go through HIV-1 RNA for the first 4 years. A similar model, but with CD4 level as mediating variable, shows a weaker indirect effect, but the results are in the same direction. There are many reasons to be cautious when drawing conclusions from estimates of direct and indirect effects. Dynamic path analysis is however a useful tool to explore underlying processes, which are ignored in regular analyses., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: By analyzing human immunodeficiency virus type 1 (HIV-1) pol sequences from the Swiss HIV Cohort Study (SHCS), we explored whether the prevalence of non-B subtypes reflects domestic transmission or migration patterns., Methods: Swiss non-B sequences and sequences collected abroad were pooled to construct maximum likelihood trees, which were analyzed for Swiss-specific subepidemics, (subtrees including ≥80% Swiss sequences, bootstrap >70%; macroscale analysis) or evidence for domestic transmission (sequence pairs with genetic distance <1.5%, bootstrap ≥98%; microscale analysis)., Results: Of 8287 SHCS participants, 1732 (21%) were infected with non-B subtypes, of which A (n = 328), C (n = 272), CRF01&#95;AE (n = 258), and CRF02&#95;AG (n = 285) were studied further. The macroscale analysis revealed that 21% (A), 16% (C), 24% (CRF01&#95;AE), and 28% (CRF02&#95;AG) belonged to Swiss-specific subepidemics. The microscale analysis identified 26 possible transmission pairs: 3 (12%) including only homosexual Swiss men of white ethnicity; 3 (12%) including homosexual white men from Switzerland and partners from foreign countries; and 10 (38%) involving heterosexual white Swiss men and females of different nationality and predominantly nonwhite ethnicity., Conclusions: Of all non-B infections diagnosed in Switzerland, <25% could be prevented by domestic interventions. Awareness should be raised among immigrants and Swiss individuals with partners from high prevalence countries to contain the spread of non-B subtypes.

The 69 insertion and Q151M mutations are multi-nucleoside/nucleotide resistance mutations (MNR). The prevalence among 4078 antiretroviral therapy (ART)-experienced individuals was <1.3%. Combined ART fully prevented MNR in subtype B infections. Case-control studies were performed to identify risk factors. Control subjects were patients with ≥ 3 thymidine-analogue mutations. The 69 insertion study (27 control subjects, 14 case patients) identified didanosine exposure as a risk (odds ratio, 5.0 per year; P = .019), whereas the Q151M study (which included 44 control subjects and 25 case patients) detected no associations. Following detection, individuals with Q151M tended to have lower suppression rates and higher mortality rates, relative to control subjects. Additional studies are needed to verify these findings in non-subtype B infections.