Marc Höglinger

Background: The erythropoietic protoporphyrias (EPP) are a group of ultra-rare (1:100.000) inborn errors of the heme biosynthesis characterised by painful phototoxic reactions in tissue exposed to visible light. Afamelanotide is the only approved treatment for EPP and effectively prevents phototoxic reactions and improves the quality of life of the patients. In the past years, several new potential treatment options for EPP have been identified, some of which are currently under investigation in clinical trials. While these developments could improve patient care, it is important to know how safety and efficacy of drug candidates compare to the existing treatment, i.e. afamelanotide. Methods: We identified pharmacotherapies (leaving out, for example, topical applications such as sunscreens or supplements such as iron) which are currently (that is, within the last 5 years) evaluated for EPP from clinical trial registries and investigated whether the trial designs allow a comparison of their treatment effects with each other and with afamelanotide. Therefore, we analysed the clinical trial protocols with emphasis on their trial designs, efficacy outcome measures, inclusion and exclusion criteria, safety aspects and, if available, published results. Results: Our search in the clinical trials registries retrieved 29 trials that included patients with EPP. From these, we identified 16 clinical trials evaluating afamelanotide and three new pharmacotherapies, i.e., dersimelagon, bitopertin and cimetidine. Safety and efficacy of all new pharmacotherapies are currently being investigated against placebo-control groups or against baseline. Because of differences in the outcome measures and included patient populations, the results of the trials cannot be directly compared. Moreover, methodically challenging aspects and ethical issues were identified in some of the trial protocols. Conclusion: Efficacy and safety of currently investigated treatments for EPP are not directly comparable. We wrote this manuscript as a call to action to Principal Investigators, Ethical Review Boards, Regulatory Authorities and the sponsors of trials because we are convinced that trials directly assessing new pharmacotherapies against afamelanotide would be the more informative, and methodological and ethically sounder trial design. Clinical trial number: Not applicable.

Background & Aim: Evidence on long-term effectiveness of diabetes disease management programs (DMPs) remains limited, with mixed findings on sustainability and cost-effectiveness. This study evaluates the long-term impact of a comprehensive DMP on quality of care and healthcare costs over six years (2018–2023). The DMP was implemented in 17 Swiss primary care practices and featured guideline-based individualized treatment plans, continuous process evaluation, interprofessional collaboration, and quality circles. We assessed the program's impact on guideline-adherent diabetes care, hospitalization, and healthcare costs over six years (2018–2023). Methods: A staggered difference-in-differences (DiD) design analyzed claims data from 2,813 patients in 17 DMP practices (treatment group) and 17,906 patients receiving usual care (control group). Outcomes included guideline-adherent diabetes care (HbA₁c monitoring, lipid profiling, nephropathy assessment, ophthalmological examination), hospitalization, and healthcare costs. The staggered DiD approach accounted for variations in implementation timing and controlled for patient- and year-fixed effects. Results: Patients in DMP practices showed a sustained 6 to 11 percentage point improvement in guideline-adherent diabetes care (95% CI for the fifth follow-up year: 8 to 14 percentage points) compared to controls. Hospitalization rates did not differ significantly between groups (95% CI for the fifth year: -0.05 to 0.00). Healthcare cost growth was significantly lower in the DMP group in years three (95% CI: CHF -2353 to -879), four (95% CI: CHF -3023 to -1419), and five (95% CI: CHF -2942 to -796), representing average cost savings exceeding 10% of total healthcare costs per patient. Conclusion: The DMP led to sustained improvements in guideline-adherent diabetes care and reduced healthcare cost growth over six years. The staggered DiD design provides robust evidence across diverse settings and implementation timelines, addressing key gaps in long-term DMP effectiveness research. These findings support broader implementation of structured DMPs for improving quality and efficiency of diabetes care in primary care settings. JEL Classification: I10, I18

Background: As part of the Covid-19-restrictions in Switzerland, a federal ban on non-urgent examinations and treatments was applied to all hospitals during six weeks in spring 2020 (“spring lockdown”). The aim of this study was to comprehensively investigate the consequences of the Covid-19 pandemic on Swiss inpatient admissions based on data of all hospitals, focusing on selected procedures of different medical urgency. Methods: The study includes all acute care inpatient cases (including Covid-19 cases, excluding cases in psychiatry and rehabilitation) according to the Swiss Medical Statistics of Hospitals. Besides the total number of admissions, subdivided by regions, hospital types and age groups, we focused on selected procedures representing different medical urgency: elective surgeries, cancer surgeries, and emergencies. Procedures were selected based on expert interviews. We compared the number of admissions during spring lockdown and for the whole years 2020 and 2021 in absolute numbers and in percentage changes to the corresponding periods in 2019 (baseline year). Results: During spring lockdown, the number of admissions decreased by 47,156 (32.2%) without catch-up effect by the end of 2020 (-72,817 admissions/-5.8%). With procedure-specific decreases of up to 86%, the decline in admissions was largest for elective surgery, a decline that was only fully reversed in the case of a few procedures, such as joint arthroplasty. Strikingly, admissions due to emergencies also substantially decreased during spring lockdown (stroke -14%; acute myocardial infarction STEMI: -9%, NSTEMI: -26%). Results for the selected procedures in cancer surgery showed no consistent pattern. In 2021, admission numbers for most procedures reached or even exceeded those in 2019. Conclusions: The substantial reduction in admissions, particularly in elective procedures, may reflect the impact of the triage in favor of anticipated Covid-19-cases during spring lockdown. By the end of 2020, admissions were still at lower levels relative to the previous, pre-pandemic year. The numbers in 2021 reached the same levels as those in 2019, which suggests that the Covid-19 pandemic only temporarily impacted inpatient health care in Switzerland. Long-term consequences of the observed reduction in admissions for emergencies and cancer surgery need to be investigated at the individual level.

Background:Telemedicine health insurance models are highly prevalent in the Swiss health care system. Nevertheless, the potential of telemedicine is only partly being achieved, since current telemedicine health insurance models are limited to an initial contact by telephone and a gatekeeper role that organizes access to health care providers such as general practitioners, specialists, or hospitals. Against this background, a telemedicine device with diverse visual and auscultatory examination functions was made available to 2,000 telemedicine-insured clients. This device allowed diagnostic information to be sent to a medical care provider and used for telemedical consultation. Objective:To determine whether the additional implementation of a multifunctional telemedicine examination device resulted in fewer physical consultations, reduced service utilization, and lower health care expenditures among telemedicine-insured clients. Methods:Our analysis is based on claims data from 135,636 clients insured in a telemedicine call center model covering the years 2019 and 2020. We compare the use of health care and health care costs of clients who received a telemedicine device with those without such a device, using multivariable regression to adjust for group differences due to self-selection. Results:We found lower total health care expenditures of −229 (Swiss Francs) and lower inpatient costs of −160 (Swiss Francs) on the part of clients with the telemedicine device. However, the implementation of the telemedicine device did not lead to a statistically significant reduction in service utilization. Conclusions:The treatment of telemedicine-insured clients was on average more cost-effective when they received the multifunctional telemedicine device. Accordingly, complementing the existing telemedicine model with telemedicine devices that allow for improved telemedical consultations has the potential to increase the cost-saving potential of the existing telemedicine call center models.

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.

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 country-wide digital proximity tracing app effectiveness assessment as guided by the WHO/ECDC framework. Specifically, we performed a descriptive analysis of the digital proximity tracing app in Switzerland for three different time periods where different SARS-CoV-2 variants of concern (i.e., Alpha, Delta, and Omicron, respectively) were most prevalent. METHODS In our study, we refer to the indicator framework for the evaluation of public health effectiveness of digital proximity tracing apps of the World Health Organization / European Center for Disease Control (WHO/ECDC). We applied this framework to compare performance and effectiveness indicators of the SwissCovid app in Switzerland across three time periods that were characterized by the dominance of the Alpha, Delta, and Omicron variants of concern. 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 in the SwissCovid app were 10%, 4%, and 5% during the Alpha, Delta, and Omicron variant phases, respectively. Following receipt of an exposure notification from the SwissCovid app, 58% (Alpha), 44% (Delta), and 73% (Omicron) of app users sought testing or performed self-tests. Test positivity among these exposure-notified individuals was 19% in the Alpha (compared with 6% in the general population), 29% (11%) in the Delta, and 41% (43%) in the Omicron variant phases. In addition, 34% (Alpha), 19% (Delta), and 30% (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. Future implementation of digital proximity tracing apps should place more emphasis on the social, psychological and organizational aspects to reduce bottlenecks and facilitate their use in pandemic situations.

Objective: To evaluate the impact of a DMP for patients with diabetes mellitus in a Swiss primary care setting. Methods: In a prospective observational study, we compared diabetes patients in a DMP (intervention group; N = 538) with diabetes patients receiving usual care (control group; N = 5050) using propensity score matching with entropy balancing. Using a difference-in-difference (DiD) approach, we compared changes in outcomes from baseline (2017) to 1-year (2017/18) and to 2-year follow-up (2017/19). Outcomes included four measures for guideline-adherent diabetes care, hospitalization risk, and health care costs. Results: We identified a positive impact of the DMP on the share of patients fulfilling all measures for guideline-adherent care [DiD 2017/18: 7.2 percentage-points, p < 0.01; 2017/19: 8.4 percentage-points, p < 0.001]. The hospitalization risk was lower in the intervention group in both years, but only statistically significant in the 1-year follow-up [DiD 2017/18: – 5.7 percentage-points, p < 0.05; 2017/19: – 3.9 percentage points, n.s.]. The increase in health care costs was smaller in the intervention than in the control group [DiD 2017/18: CHF – 852; 2017/19: CHF – 909], but this effect was not statistically significant. Conclusion: The DMP under evaluation seems to exert a positive impact on the quality of diabetes care, reflected in the increase in the measures for guideline-adherent care and in a reduction of the hospitalization risk in the intervention group. It also might reduce health care costs, but only a longer follow-up will show whether the observed effect persists over time.

Background: Mitigation of the spread of infection relies on targeted approaches aimed at preventing nonhousehold interactions. Contact tracing in the form of digital proximity tracing apps has been widely adopted in multiple countries due to its perceived added benefits of tracing speed and breadth in comparison to traditional manual contact tracing. Assessments of user responses to exposure notifications through a guided approach can provide insights into the effect of digital proximity tracing app use on managing the spread of SARS-CoV-2. Objective: The aim of this study was to demonstrate the use of Venn diagrams to investigate the contributions of digital proximity tracing app exposure notifications and subsequent mitigative actions in curbing the spread of SARS-CoV-2 in Switzerland. Methods: We assessed data from 4 survey waves (December 2020 to March 2021) from a nationwide panel study (COVID-19 Social Monitor) of Swiss residents who were (1) nonusers of the SwissCovid app, (2) users of the SwissCovid app, or (3) users of the SwissCovid app who received exposure notifications. A Venn diagram approach was applied to describe the overlap or nonoverlap of these subpopulations and to assess digital proximity tracing app use and its associated key performance indicators, including actions taken to prevent SARS-CoV-2 transmission. Results: We included 12,525 assessments from 2403 participants, of whom 50.9% (1222/2403) reported not using the SwissCovid digital proximity tracing app, 49.1% (1181/2403) reported using the SwissCovid digital proximity tracing app and 2.5% (29/1181) of the digital proximity tracing app users reported having received an exposure notification. Most digital proximity tracing app users (75.9%, 22/29) revealed taking at least one recommended action after receiving an exposure notification, such as seeking SARS-CoV-2 testing (17/29, 58.6%) or calling a federal information hotline (7/29, 24.1%). An assessment of key indicators of mitigative actions through a Venn diagram approach reveals that 30% of digital proximity tracing app users (95% CI 11.9%-54.3%) also tested positive for SARS-CoV-2 after having received exposure notifications, which is more than 3 times that of digital proximity tracing app users who did not receive exposure notifications (8%, 95% CI 5%-11.9%). Conclusions: Responses in the form of mitigative actions taken by 3 out of 4 individuals who received exposure notifications reveal a possible contribution of digital proximity tracing apps in mitigating the spread of SARS-CoV-2. The application of a Venn diagram approach demonstrates its value as a foundation for researchers and health authorities to assess population-level digital proximity tracing app effectiveness by providing an intuitive approach for calculating key performance indicators.

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.

BACKGROUND Mitigation of the spread of infection relies on targeted approaches aimed at preventing nonhousehold interactions. Contact tracing in the form of digital proximity tracing apps has been widely adopted in multiple countries due to its perceived added benefits of tracing speed and breadth in comparison to traditional manual contact tracing. Assessments of user responses to exposure notifications through a guided approach can provide insights into the effect of digital proximity tracing app use on managing the spread of SARS-CoV-2. OBJECTIVE The aim of this study was to demonstrate the use of Venn diagrams to investigate the contributions of digital proximity tracing app exposure notifications and subsequent mitigative actions in curbing the spread of SARS-CoV-2 in Switzerland. METHODS We assessed data from 4 survey waves (December 2020 to March 2021) from a nationwide panel study (COVID-19 Social Monitor) of Swiss residents who were (1) nonusers of the SwissCovid app, (2) users of the SwissCovid app, or (3) users of the SwissCovid app who received exposure notifications. A Venn diagram approach was applied to describe the overlap or nonoverlap of these subpopulations and to assess digital proximity tracing app use and its associated key performance indicators, including actions taken to prevent SARS-CoV-2 transmission. RESULTS We included 12,525 assessments from 2403 participants, of whom 50.9% (1222/2403) reported not using the SwissCovid digital proximity tracing app, 49.1% (1181/2403) reported using the SwissCovid digital proximity tracing app and 2.5% (29/1181) of the digital proximity tracing app users reported having received an exposure notification. Most digital proximity tracing app users (75.9%, 22/29) revealed taking at least one recommended action after receiving an exposure notification, such as seeking SARS-CoV-2 testing (17/29, 58.6%) or calling a federal information hotline (7/29, 24.1%). An assessment of key indicators of mitigative actions through a Venn diagram approach reveals that 30% of digital proximity tracing app users (95% CI 11.9%-54.3%) also tested positive for SARS-CoV-2 after having received exposure notifications, which is more than 3 times that of digital proximity tracing app users who did not receive exposure notifications (8%, 95% CI 5%-11.9%). CONCLUSIONS Responses in the form of mitigative actions taken by 3 out of 4 individuals who received exposure notifications reveal a possible contribution of digital proximity tracing apps in mitigating the spread of SARS-CoV-2. The application of a Venn diagram approach demonstrates its value as a foundation for researchers and health authorities to assess population-level digital proximity tracing app effectiveness by providing an intuitive approach for calculating key performance indicators.