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While several studies proved the relationship between increasing temperatures and poor mental health, limited evidence exists on the effect of other weather factors, such as precipitation. This study assessed the impact of precipitation on hospital admissions for mental disorders in Switzerland between 2009–2019. We defined different precipitation events based on the duration (daily precipitation ≥1mm for 2, 3, or 4 days; PP.2/PP.3/PP.4) and intensity (≥90th percentile for 2 consecutive days; PEP90.2). First, we conducted aggregated time-stratified case-crossover analysis in eight main Swiss cities with distributed lag models to assess the association up to 3 days after the exposure. Then, we pooled the estimates in each city using a multivariate random effects meta-analysis for all hospital admissions and by subgroups (sex, age, diagnosis). Evidence of an association between precipitation and hospital admission for mental disorders was not found in Switzerland (PP.2: 1.003[0.978–1.029]; PP.3: 1.005[0.985–1.026]; PP.4: 0.994[0.960–1.030]; PEP90.2: 1.000[0.953–1.050]). Although the results were highly uncertain, we found an indication of increasing risks of hospital admission with increasing intensity of precipitation in warmer seasons (PP.2: 1.001[0.971–1.032] vs PEP90.2: 1.014[0.955–1.078]), while the risks of hospital admission slightly increased by the duration in colder season (PP.2: 1.009[0.981–1.039]; PP.3: 1.008[0.980–1.036]; PP.4: 1.017[0.956–1.081]). Overall, risks tend to be higher in people aged < 65 years. Duration of the events may influence more than intensity in females, while opposite patterns were observed in males. Risks tended to be larger but still uncertain for schizophrenia, mood disorders, and adult personality disorders. An indication of a negative association was found in neurotic disorders and null risks in the remaining groups. Although our findings did not show a clear association between precipitation and mental disorders, further research is required to clarify the role of precipitation and the potential implications of climate change and extreme precipitation events on mental health.

Introduction The availability of consumer-facing health technologies for chronic disease management is skyrocketing, yet most are limited by low adoption rates. Improving adoption requires a better understanding of a target population's previous exposure to technology. We propose a low-resource approach of capturing and clustering technology exposure, as a mean to better understand patients and target health technologies. Methods Using Multiple Sclerosis (MS) as a case study, we applied exploratory multivariate factorial analyses to survey data from the Swiss MS Registry. We calculated individual-level factor scorings, aiming to investigate possible technology adoption clusters with similar digital behavior patterns. The resulting clusters were transformed using radar and then compared across sociodemographic and health status characteristics. Results Our analysis included data from 990 respondents, resulting in three clusters, which we defined as the (1) average users, (2) health-interested users, and (3) low frequency users. The average user uses consumer-facing technology regularly, mainly for daily, regular activities and less so for health-related purposes. The health-interested user also uses technology regularly, for daily activities as well as health-related purposes. The low-frequency user uses technology infrequently. Conclusions Only about 10% of our sample has been regularly using (adopting) consumer-facing technology for MS and health-related purposes. That might indicate that many of the current consumer-facing technologies for MS are only attractive to a small proportion of patients. The relatively low-resource exploratory analyses proposed here may allow for a better characterization of prospective user populations and ultimately, future patient-facing technologies that will be targeted to a broader audience., PLoS ONE, 18 (4), ISSN:1932-6203

Background Rapid diagnostics are vital for curving the transmission and control of the COVID-19 pandemic. Although many commercially available antigen-based rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 are recommended by the WHO, their diagnostic performance has not yet been assessed in Ethiopia. So far, the vast majority of studies assessing diagnostic accuracies of rapid antigen tests considered RT-PCR as a reference standard, which inevitably leads to bias when RT-PCR is not 100% sensitive and specific. Thus, this study aimed to evaluate the diagnostic performance of Panbio™ jointly with the RT-PCR for the detection of SARS-CoV-2. Methods A prospective cross-sectional study was done from July to September 2021 in Addis Ababa, Ethiopia, during the third wave of the pandemic involving two health centers and two hospitals. Diagnostic sensitivity and specificity of Panbio™ and RT-PCR were obtained using Bayesian Latent-Class Models (BLCM). Results 438 COVID-19 presumptive clients were enrolled, 239 (54.6%) were females, of whom 196 (44.7%) had a positive RT-PCR and 158 (36.1%) were Panbio™ positive. The Panbio™ and RT-PCR had a sensitivity (95% CrI) of 99.6 (98.4–100) %, 89.3 (83.2–97.6) % and specificity (95% CrI) of 93.4 (82.3–100) %, and 99.1 (97.5–100) %, respectively. Most of the study participants, 318 (72.6%) exhibited COVID-19 symptoms; the most reported was cough 191 (43.6%). Conclusion As expected the RT-PCR performed very well with a near-perfect specificity and a high, but not perfect sensitivity. The diagnostic performance of Panbio™ is coherent with the WHO established criteria of having a sensitivity ≥80% for Ag-RDTs. Both tests displayed high diagnostic accuracies in patients with and without symptoms. Hence, we recommend the use of the Panbio™ for both symptomatic and asymptomatic individuals in clinical settings for screening purposes.

Aims of the study Since 2014, the Swiss Hepatitis Strategy (SHS) has targeted the elimination of Hepatitis C Virus (HCV) in Switzerland. The epidemiology of HCV is diverse across Swiss cantons, therefore cantonal-level screening and treatment strategies should be developed. This study aimed to identify scenarios to achieve HCV elimination in the canton of Bern by 2030. Methods A preexisting Markov disease burden model was populated with data for Bern, and used to forecast the current and future prevalence of HCV, annual liver-related deaths (LRDs), and incidence of hepatocellular carcinoma and decompensated cirrhosis until 2030. Scenarios were developed to assess the current standard of care and potential long-term impact of the COVID-19 crisis on the HCV infected population. Additionally, potential scenarios for achieving the WHO 2030 targets and the SHS 2025 and 2030 targets (reduction of new cases of HCV, HCV-related mortality and viremic HCV cases) were identified. Results In 2019, there were an estimated 4,600 (95% UI: 3,330–4,940) viremic infections in the canton of Bern and 57% (n = 2,600) of viremic cases were diagnosed. This modelling forecasted a 10% increase in LRDs (28 in 2020 to 31 in 2030) with the current standard of care and a 50% increase in LRDs in a scenario assuming long-term delays. To achieve the WHO and SHS targets, the canton of Bern needs to increase the annual number of patients diagnosed (from 90 in 2019 to 250 per year in 2022–2024 [WHO], or 500 per year in 2022–2025 [SHS]) and treated (from 130 in 2019 to 340 per year in 2022–2024 [WHO] or 670 per year in 2022–2025 [SHS]). Conclusions The SHS goals and the WHO targets for HCV elimination can be achieved in the Swiss canton of Bern by 2030; however, not at the current pace of screening, linkage to care and treatment.

Background and objectives Blast-induced lung injury is associated with inflammatory, which are characterised by disruption of the alveolar-capillary barrier, haemorrhage, pulmonary infiltrateration causing oedema formation, pro-inflammatory cytokine and chemokine release, and anti-inflammatory counter-regulation. The objective of the current study was to define sequence of such alterations in with establishing blast-induced lung injury in rats using an advanced blast generator. Methods Rats underwent a standardized blast wave trauma and were euthanised at defined time points. Non-traumatised animals served as sham controls. Obtained samples from bronchoalveolar lavage fluid (BALF) at each time-point were assessed for histology, leukocyte infiltration and cytokine/chemokine profile. Results After blast lung injury, significant haemorrhage and neutrophil infiltration were observed. Similarly, protein accumulation, lactate dehydrogenase activity (LDH), alveolar eicosanoid release, matrix metalloproteinase (MMP)-2 and -9, pro-Inflammatory cytokines, including tumour necrosis factor (TNF) and interleukin (IL) -6 raised up. While declining in the level of anti-inflammatory cytokine IL-10 occurred. Ultimately, pulmonary oedema developed that increased to its maximum level within the first 1.5 h, then recovered within 24 h. Conclusion Using a stablished model, can facilitate the study of inflammatory response to blast lung injury. Following the blast injury, alteration in cytokine/chemokine profile and activity of cells in the alveolar space occurs, which eventuates in alveolar epithelial barrier dysfunction and oedema formation. Most of these parameters exhibit time-dependent return to their basal status that is an indication to resilience of lungs to blast-induced lung injury.

Stevia rebaudiana (stevia) contains commercially important steviol glycosides, stevioside and rebaudioside A, these compounds have insulinotropic and anti-hyperglycemic effect. Steviol, stevioside and rebaudioside-A have taste modulation and insulin potentiation activity. Stevia leaves are composed of steviol (2–5%), stevioside (4–13%) and rebaudioside-A (1–6%). Stevioside has after-taste bitterness, rebaudioside-A is sweetest in taste among all the glycosides present. Therefore, lower ratio of rebaudioside-A to stevioside has bitter after-taste, which makes stevia plants unpalatable. By over-expressing the genes, SrUGT76G1 and SrKO, we propose to increase the ratio of RebA to stevioside in stevia. Various lines were generated and amongst them, seven lines had both the transgenes present. Co-overxpresion of SrUGT76G1 and SrKO led to the increased concentration of RebA in all the seven transgenic lines (KU1-KU7) than control plant and RebA to stevioside ratio also increased significantly. Steviol, stevioside and RebA showed a differential concentration in all the seven lines, but the pattern was the same in all of them and the ratio of RebA to stevioside increased dramatically. In transgenic line 2 (KU2), RebA showed a steep increase in concentration 52% the rebaudioside-A to stevioside ratio increased from 0.74 (control) to 2.83. In overall all the lines, RebA showed a positive correlation with steviol and stevioside. Overexpression of SrKO led to an increase in steviol which increased the stevioside, overexpression of SrUGT76G1 ultimately increased RebA concentration. In conclusion, concentration of RebA increased significantly with co- overexpression of SrUGT6G1 and SrKO genes. Lines with increased RebA are more palatable and commercially viable.

Background During critical care procedural skills training (e.g., in intubation and pericardiocentesis) the appropriate supervision level is important to ensure correct use of techniques and guarantee patient safety. The appropriate teaching style should be selected to address residents’ learning behavior and foster their competence. The aim of this study was to explore the number of repetitions for given skills needed to achieve a specified supervision level and a specific teaching style. Methods This cross-sectional multicenter survey obtained data from residents and faculty of three multidisciplinary intensive care units (ICU) in Switzerland. Using a 4-point Likert scale, participants were asked to indicate the number of repetitions required to achieve the specified supervision level and teaching style. Results Among 91 physicians, the response rate was 64% (n = 59). Their median estimations of the numbers of skill repetitions needed to achieve the final fourth level of supervision and final fourth stage of teaching style were as follows: arterial catheter insertion: supervision level 32, teaching style 17.5; peritoneal paracentesis: supervision level 27, teaching style 17; central venous catheter insertion: supervision level 38, teaching style 28; lumbar puncture: supervision level 38, teaching style 21; endotracheal intubation: supervision level 100, teaching style 45; chest drain insertion: supervision level 27, teaching style 21.5; temporary pacemaker placement: supervision level 50, teaching style 19.5; percutaneous tracheostomy: supervision level 50, teaching style 29; pericardiocentesis: supervision level 50, teaching style 35. Comparison of repetitions between supervision level and teaching style revealed no difference at the first and second levels, except for endotracheal intubation at level 2 (p = 0.03). Differences were observed at the third and fourth levels of supervision level and teaching style (p≤0.04). Conclusions It appears that the supervision level and teaching style applied by faculty should change according to both the number of repetitions and the difficulty of critical care procedural skills.

During the first year of the COVID-19 pandemic, healthcare facilities worldwide struggled to adequately care for the increasing number of COVID-19 patients while maintaining quality of care for all other patients. The aim of this study was to investigate the displacement and underuse of non-COVID-19 patient care in a medical department of a tertiary hospital in Switzerland. In this retrospective cross-sectional study, internal medicine admissions from 2017 to 2020, emergency outpatient visits from 2019 to 2020 and COVID-19 admissions in 2020 were analyzed and compared using a regression model. Internal medicine admissions were also stratified by diagnosis. A questionnaire was used to assess the pandemic experience of local general practitioners, referring hospitals, and nursing homes. The total number of admissions decreased during the 1st and 2nd waves of the pandemic but increased between the two waves. Elective admissions decreased in 2020 compared to pre-pandemic years: they represented 25% of total admissions in 2020 versus 30% of the total admissions during 2017–2019, p

Background Accurate breath detection is essential for the computation of outcomes in the multiple-breath washout (MBW) technique. This is particularly important in young children, where irregular breathing is common, and the designation of inspirations and expirations can be challenging. Aim To investigate differences between a commercial and a novel breath-detection algorithm and to characterize effects on MBW outcomes in children. Methods We replicated the signal processing and algorithms used in Spiroware software (v3.3.1, Eco Medics AG). We developed a novel breath detection algorithm (custom) and compared it to Spiroware using 2,455 nitrogen (N2) and 325 sulfur hexafluoride (SF6) trials collected in infants, children, and adolescents. Results In 83% of N2 and 32% of SF6 trials, the Spiroware breath detection algorithm rejected breaths and did not use them for the calculation of MBW outcomes. Our custom breath detection algorithm determines inspirations and expirations based on flow reversal and corresponding CO2 elevations, and uses all breaths for data analysis. In trials with regular tidal breathing, there were no differences in outcomes between algorithms. However, in 10% of pre-school children tests the number of breaths detected differed by more than 10% and the commercial algorithm underestimated the lung clearance index by up to 21%. Conclusion Accurate breath detection is challenging in young children. As the MBW technique relies on the cumulative analysis of all washout breaths, the rejection of breaths should be limited. We provide an improved algorithm that accurately detects breaths based on both flow reversal and CO2 concentration.

Aims The Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods and results Using a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE. Conclusions In real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts. ClinicalTrials.gov identifier NCT02241291.

Introduction There is a substantial geographical variation in the rates of pacemaker (PM), implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy (CRT) device implantation across European countries. We assessed the extent of regional variation and potential determinants of such variation. Methods We conducted a population-based analysis using discharge data for PM/ICD/CRT implantations from all Swiss acute care hospitals during 2013–2016. We derived hospital service areas (HSA) by analyzing patient flows. We calculated age- and sex-standardized rates and quantified variation using the extremal quotient (EQ) and the systemic component of variation (SCV). We estimated the reduction in variance of crude implantation rates across HSAs using multilevel regression models, with incremental adjustment for age and sex, language, socioeconomic factors, population health, diabetes mellitus, and the density of cardiologists on the HSA level. Results We analyzed implantations of 8129 PM, 1461 ICD, and 1411 CRT from 25 Swiss HSAs. The mean age- and sex-standardized implantation rate was 29 (range 8–57) per 100,000 persons for PM, 5 (1–9) for ICD, and 5 (2–8) for CRT. There was a very high variation in PM (EQ 7.0; SCV 12.6) and ICD (EQ 7.2; SCV 11.3) and a high variation in CRT implantation rates (EQ 3.9; SCV 7.1) across HSAs. Adjustments for age and sex, language, socioeconomic factors, population health, diabetes mellitus, and density of cardiologists explained 94% of the variance in ICD and 87.5% of the variance in CRT implantation rates, but only 36.3% of the variance in PM implantation rates. Women had substantially lower PM/ICD/CRT implantation rates than men. Conclusion Switzerland has a very high regional variation in PM/ICD implantation and a high variation in CRT implantation rates. Women had substantially lower implantation rates than men. A large share of the variation in PM procedure rates remained unexplained which might reflect variations in physicians’ preferences and practices.

Socioeconomic conditions across the life course may contribute to differences in multimorbidity and polypharmacy in old age. However, whether the risk of multimorbidity changes during ageing and whether life-course socioeconomic conditions are associated with polypharmacy remain unclear. We investigated whether disadvantaged childhood socioeconomic conditions (CSCs) predict increased odds of multimorbidity and polypharmacy in older adults, whether CSCs remain associated when adjusting for adulthood socioeconomic conditions (ACSs), and whether CSCs and ACSs are associated cumulatively over the life course. We used data for 31,432 participants (multimorbidity cohort, mean [SD] age 66·2[9] years), and 21,794 participants (polypharmacy cohort, mean age 69·0[8.9] years) from the Survey of Health, Ageing, and Retirement in Europe (age range 50–96 years). We used mixed-effects logistic regression to assess the associations of CSCs, ASCs, and a life-course socioeconomic conditions score (0–8; 8, most advantaged) with multimorbidity (≥2 chronic conditions) and polypharmacy (≥5 drugs taken daily). We found an association between CSCs and multimorbidity (reference: most disadvantaged; disadvantaged: odds ratio (OR) = 0·79, 95% confidence interval (CI) 0·70–0·90; middle: OR = 0·60; 95%CI 0·53–0·68; advantaged: OR = 0·52, 95%CI 0·45–0·60, most advantaged: OR = 0·40, 95%CI 0·34–0·48) but not polypharmacy. This multimorbidity association was attenuated but remained significant after adjusting for ASCs. The life-course socioeconomic conditions score was associated with multimorbidity and polypharmacy. We did not find an association between CSCs, life-course socioeconomic conditions, and change in odds of multimorbidity and polypharmacy with ageing. Exposure to disadvantaged socioeconomic conditions in childhood or over the entire life-course could predict multimorbidity in older age.

Cardiolipin is known to interact with bacterial and mitochondrial proteins and protein complexes. Unlike in Escherichia coli and Saccharomyces cerevisiae, the synthesis of cardiolipin is essential for growth of Trypanosoma brucei parasites in culture. Inhibition of cardiolipin production has been shown to result in major changes in the T. brucei proteome and energy metabolism, with CLDP43, a mitochondrial protein containing a StaR-related lipid transfer (START)-like domain, being depleted in a cardiolipin-dependent way. We now show that in T. brucei procyclic forms lacking CLDP43, cardiolipin metabolism and mitochondrial function are affected. Using quantitative and qualitative lipid analyses, we found that while steady-state levels of cardiolipin were elevated in CLDP43 knock-out parasites compared to parental cells, de novo formation of cardiolipin was down-regulated. In addition, depletion of CLDP43 resulted in partial loss of mitochondrial membrane potential and decreased ATP production via substrate level phosphorylation. Recombinant CLDP43 was found to bind cardiolipin and phosphatidic acid in lipid overlay experiments, suggesting that it may be involved in transport or synthesis of cardiolipin or its precursors in T. brucei.

Background The COVID-19 pandemic and associated restrictions have led to abrupt changes in the lives of elite athletes. Objectives The objective of this prospective cohort study was to examine training load, subjective sports performance, physical and mental health among Swiss elite athletes during a 6-month follow-up period starting with the first Swiss lockdown. Methods Swiss elite athletes (n = 203) participated in a repeated online survey evaluating health, training, and performance related metrics. After the first assessment during the first lockdown between April and May 2020, there were monthly follow-ups over 6 months. Results Out of 203 athletes completing the first survey during the first lockdown, 73 athletes (36%) completed all assessments during the entire 6-month follow-up period. Sports performance and training load decreased during the first lockdown and increased again at the beginning of the second lockdown in October 2020, while symptoms of depression and financial fears showed only a transient increase during the first lockdown. Self-reported injuries and illnesses did not change significantly at any timepoint in the study. Stricter COVID-19 restrictions, as measured by the Government Stringency Index (GSI), were associated with reduced subjective sports performance, as well as lower training intensity, increased financial fears, poorer coping with restrictions, and more depressive symptoms, as measured by the 9-item module of the Patient Health Questionnaire-9 (PHQ-9). Conclusion This study revealed a negative impact of the COVID-19 restrictions on sports performance, training load and mental health among Swiss elite athletes, while the rate of self-reported injuries and illnesses remained unaffected.

Brucellosis is one of the main livestock disease risks in Kazakhstan. It’s been endemic there since 1930, accounting for over 1300 human cases per annum. The economic loss was 45 million USD in 2015 alone. Since 1952, Kazakhstan has implemented various control strategies with little success. One Health approaches have been suggested to tackle brucellosis, however, there is a lack of evidence for best practices to operationalise One Health in the literature, and methods for implementation are not established. The intention of this study was to introduce the One Health approach during the evaluation phase of the policy cycle. A two-day workshop was organized by the authors to familiarize participants with the evaluation methodology. Twenty-one specialists representing veterinary and public health sector, together with researchers, took part in this study. For two weeks following the workshop, first author conducted individual interviews with workshop participants to obtain individual scorings to assess knowledge integration capacity (One Health-ness). The evaluation results show that there is a lack of knowledge about the perceived damage caused by brucellosis to animal owners and other stakeholders. There is insufficient data available about farmers’ practices, interests and motivations, and also data is missing for important transmission processes such as the amount of unsafe dairy consumption. The absence of such data illustrates the extent of the uncertainty to which decision-makers are exposed despite well-elaborated transmission models and supports the importance of co-producing solutions with participatory methods. The results suggest the need for broader involvement of stakeholders. Outputs of this study could help navigate the initial stages of One Health operationalization.

During analysis of a prospective multinational observation study of critically ill patients ≥80 years of age, the VIP2 study, we also studied the effects of differences in country consent for study inclusion. This is a post hoc analysis where the ICUs were analyzed according to requirement for study consent. Group A: ICUs in countries with no requirement for consent at admission but with deferred consent in survivors. Group B: ICUs where some form of active consent at admission was necessary either from the patient or surrogates. Patients’ characteristics, the severity of disease and outcome variables were compared. Totally 3098 patients were included from 21 countries. The median age was 84 years (IQR 81-87). England was not included because of changing criteria for consent during the study period. Group A (7 countries, 1220 patients), and group B (15 countries, 1878 patients) were comparable with age distribution, organ failure score, frailty score and activity of daily life. Cognition was better preserved prior to admission in group B. Group A suffered from more organ dysfunction at admission compared to group B with Sequential Organ Failure Assessment score median 8 and 5 respectively. Survival at 30-day was lower in group A, 50.8 % compared to 66.7% in group B (pWe therefore conclude that consent likely is an important confounding factor for outcome evaluation in international studies focusing on old patients.

In recent years, insect husbandry has seen an increased interest in order to supply in the production of raw materials, food, or as biological/environmental control. Unfortunately, large insect rearings are susceptible to pathogens, pests and parasitoids which can spread rapidly due to the confined nature of a rearing system. Thus, it is of interest to monitor the spread of such manifestations and the overall population size quickly and efficiently. Medical imaging techniques could be used for this purpose, as large volumes can be scanned non-invasively. Due to its 3D acquisition nature, computed tomography seems to be the most suitable for this task. This study presents an automated, computed tomography-based, counting method for bee rearings that performs comparable to identifying all Osmia cornuta cocoons manually. The proposed methodology achieves this in an average of 10 seconds per sample, compared to 90 minutes per sample for the manual count over a total of 12 samples collected around lake Zurich in 2020. Such an automated bee population evaluation tool is efficient and valuable in combating environmental influences on bee, and potentially other insect, rearings.

BackgroundInappropriate polypharmacy has been linked with adverse outcomes in older, multimorbid adults. OPERAM is a European cluster-randomized trial aimed at testing the effect of a structured pharmacotherapy optimization intervention on preventable drug-related hospital admissions in multimorbid adults with polypharmacy aged 70 years or older. Clinical results of the trial showed a pattern of reduced drug-related hospital admissions, but without statistical significance. In this study we assessed the cost-effectiveness of the pharmacotherapy optimisation intervention.MethodsWe performed a pre-planned within-trial cost-effectiveness analysis (CEA) of the OPERAM intervention, from a healthcare system perspective. All data were collected within the trial apart from unit costs. QALYs were computed by applying the crosswalk German valuation algorithm to EQ-5D-5L-based quality of life data. Considering the clustered structure of the data and between-country heterogeneity, we applied Generalized Structural Equation Models (GSEMs) on a multiple imputed sample to estimate costs and QALYs. We also performed analyses by country and subgroup analyses by patient and morbidity characteristics.ResultsTrial-wide, the intervention was numerically dominant, with a potential cost-saving of CHF 3’588 (95% confidence interval (CI): -7’716; 540) and gain of 0.025 QALYs (CI: -0.002; 0.052) per patient. Robustness analyses confirmed the validity of the GSEM model. Subgroup analyses suggested stronger effects in people at higher risk.ConclusionWe observed a pattern towards dominance, potentially resulting from an accumulation of multiple small positive intervention effects. Our methodological approaches may inform other CEAs of multi-country, cluster-randomized trials facing presence of missing values and heterogeneity between centres/countries.

Background Large households/families may create more happiness and offer more comprehensive healthcare among the members. We correlated household size to dementia mortality rate at population level for analysing its protecting role against dementia mortality. Methods This is a retrospective cross-sectional study. Dementia specific mortality rates of the 183 member states of World Health Organization were calculated and matched with the respective country data on household size, Gross Domestic Product (GDP), urban population and ageing. Scatter plots were produced to explore and visualize the correlations between household size and dementia mortality rates. Pearson’s and nonparametric correlations were used to evaluate the strength and direction of the associations between household size and all other variables. Partial correlation of Pearson’s approach was used to identify that household size protects against dementia regardless of the competing effects from ageing, GDP and urbanization. Multiple regression was used to identify significant predictors of dementia mortality. Results Household size was in a negative and moderately strong correlation (r = -0.6034, p < 0.001) with dementia mortality. This relationship was confirmed in both Pearson r (r = - 0.524, p2 = 0.263 while ageing was placed second increasing R2 to 0.259. GDP and urbanization were removed as having no statistically significant influence on dementia mortality. Conclusions While acknowledging ageing, urban lifestyle and greater GDP associated with dementia mortality, this study suggested that, at population level, household size was another risk factor for dementia mortality. As part of dementia prevention, healthcare practitioners should encourage people to increase their positive interactions with persons from their neighbourhood or other fields where large household/family size is hard to achieve.

Introduction Studies on effectiveness of cardiac rehabilitation (CR) in elderly cardiovascular disease patients are rare, and it is unknown, which patients benefit most. We aimed to identify predictors for 1-year outcomes of cardiorespiratory fitness and CV risk factor (CVRF) control in patients after completing CR programs offered across seven European countries. Methods Cardiovascular disease patients with minimal age 65 years who participated in comprehensive CR were included in this observational study. Peak oxygen uptake (VO2), body mass index (BMI), resting systolic blood pressure (BPsys), and low-density lipoprotein-cholesterol (LDL-C) were assessed before CR (T0), at termination of CR (T1), and 12 months after start of CR (T2). Predictors for changes were identified by multivariate regression models. Results Data was available from 1241 out of 1633 EU-CaRE patients. The strongest predictor for improvement in peak VO2 was open chest surgery, with a nearly four-fold increase in surgery compared to non-surgery patients. In patients after surgery, age, female sex, physical inactivity and time from index event to T0 were negative predictors for improvement in peak VO2. In patients without surgery, previous acute coronary syndrome and higher exercise capacity at T0 were the only negative predictors. Neither number of attended training sessions nor duration of CR were significantly associated with change in peak VO2. Non-surgery patients were more likely to achieve risk factor targets (BPsys, LDL-C, BMI) than surgery patients. Conclusions In a previously understudied population of elderly CR patients, time between index event and start of CR in surgery and disease severity in non-surgery patients were the most important predictors for long-term improvement of peak VO2. Non-surgery patients had better CVRF control.

BackgroundSwitzerland 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.MethodsWe 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.ResultsWe 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.DiscussionAs 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.

PurposeTo determine the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) on clinical management in patients with suspected mycotic aortic aneurysms (MAA).Materials and methodsFor this observational cohort study 101 PET/CT were acquired in 50 patients, thereof 50 for the initial diagnosis/baseline scan, 51 for follow-up. Impact on patient management was defined in three categories: PET/CT results were "confirmed" (by clinical follow-up), "suspected" (conclusive, not confirmed), or "misleading" (proven wrong by follow-up). For clinical follow-up patient data were recorded at the time of imaging, and at the latest recorded clinical visit. It included patient demographics, clinical information, laboratory data, results of microbiology and other diagnostic procedures, information about treatment, and patient's general health condition.ResultsIn four patients (8%) no clinical follow-up was feasible, the other 46 patients were clinically followed for a median of 898 days (IQR 320-4105). The combined evaluation of all 101 PET/CT demonstrated an impact on patient management in 78,5% of cases (48,5% confirmed, 30% suspected). Results of 21,5% of the PET/CT examinations were misleading. Respective values at baseline and at follow-up were: impact on patient management in 82% and 74,5% (70% and 27.5% confirmed, and 12% and 47% suspected), misleading cases in 18% and 25.5%.ConclusionIn MAA, PET/CT has a high impact on patient management, which is more pronounced with baseline than with follow-up examinations. However, PET/CT results may be misleading in a smaller proportion of cases.

Background Older adults with chronic conditions are at high risk of complications from influenza and pneumococcal infections. Evidence about factors associated with influenza and pneumococcal vaccination among older multimorbid persons in Europe is limited. The aim of this study was to investigate the prevalence and determinants of these vaccinations in this population. Methods Multimorbid patients aged ≥70 years with polypharmacy were enrolled in 4 European centers in Switzerland, Belgium, the Netherlands, and Ireland. Data on vaccinations, demographics, health care contacts, and comorbidities were obtained from self-report, general practitioners and medical records. The association of comorbidities or medical contacts with vaccination status was assessed using multivariable adjusted log-binomial regression models. Results Among 1956 participants with available influenza vaccination data (median age 79 years, 45% women), 1314 (67%) received an influenza vaccination within the last year. Of 1400 patients with available pneumococcal vaccination data (median age 79 years, 46% women), prevalence of pneumococcal vaccination was 21% (n = 291). The prevalence of vaccination remained low in high-risk populations with chronic respiratory disease (34%) or diabetes (24%), but increased with an increasing number of outpatient medical contacts. Chronic respiratory disease was independently associated with the receipt of both influenza and pneumococcal vaccinations (prevalence ratio [PR] 1.09, 95% confidence interval [CI] 1.03–1.16; and PR 2.03, 95%CI 1.22–3.40, respectively), as was diabetes (PR 1.06, 95%CI 1.03–1.08; PR 1.24, 95%CI 1.16–1.34, respectively). An independent association was found between number of general practitioner visits and higher prevalence of pneumococcal vaccination (p for linear trend Conclusion Uptake of influenza and particularly of pneumococcal vaccination in this population of European multimorbid older inpatients remains insufficient and is determined by comorbidities and number and type of health care contacts, especially outpatient medical visits. Hospitalization may be an opportunity to promote vaccination, particularly targeting patients with few outpatient physician contacts.

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

Background Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity. Methods We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn’s disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design. Results Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients. Conclusion As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma.

Chronic inflammation and blood–brain barrier dysfunction are key pathological hallmarks of neurological disorders such as multiple sclerosis, Alzheimer’s disease and Parkinson’s disease. Major drivers of these pathologies include pro-inflammatory stimuli such as prostaglandins, which are produced in the central nervous system by the oxidation of arachidonic acid in a reaction catalyzed by the cyclooxygenases COX1 and COX2. Monoacylglycerol lipase hydrolyzes the endocannabinoid signaling lipid 2-arachidonyl glycerol, enhancing local pools of arachidonic acid in the brain and leading to cyclooxygenase-mediated prostaglandin production and neuroinflammation. Monoacylglycerol lipase inhibitors were recently shown to act as effective anti-inflammatory modulators, increasing 2-arachidonyl glycerol levels while reducing levels of arachidonic acid and prostaglandins, including PGE2 and PGD2. In this study, we characterized a novel, highly selective, potent and reversible monoacylglycerol lipase inhibitor (MAGLi 432) in a mouse model of lipopolysaccharide-induced blood–brain barrier permeability and in both human and mouse cells of the neurovascular unit: brain microvascular endothelial cells, pericytes and astrocytes. We confirmed the expression of monoacylglycerol lipase in specific neurovascular unit cells in vitro, with pericytes showing the highest expression level and activity. However, MAGLi 432 did not ameliorate lipopolysaccharide-induced blood–brain barrier permeability in vivo or reduce the production of pro-inflammatory cytokines in the brain. Our data confirm monoacylglycerol lipase expression in mouse and human cells of the neurovascular unit and provide the basis for further cell-specific analysis of MAGLi 432 in the context of blood–brain barrier dysfunction caused by inflammatory insults.

Background Interaction with fish is known to reduce stress and anxiety in humans. Objective This trial evaluated the effect of an aquarium present in a geriatric dental clinic waiting-area (WA) on blood pressure (BP), heart-rate (HR), anxiety, and mood of waiting patients. Methods Participants were recruited into three groups: control (CG): WA without aquarium; partially-stocked aquarium (PSA): aquarium without fish; fully-stocked aquarium (FSA): aquarium with fish. BP and HR of the participants were recorded upon arrival and after 20-minutes of waiting, along with anxiety [State trait anxiety inventory (STAI-6)] and mood [Feeling scale (FS), Felt arousal scale (FAS)] scores. A purpose-built questionnaire evaluated the subjective assessment of the participants’ experience in the WA. ANOVA with repeated measures and nonparametric tests were used for statistical analysis (p Results 392 patients (mean age: 65.07±16.9y) completed this trial. There was an effect of time on the BP [systolic: F(1, 120) = 44.82, p Conclusions There was no influence of the presence of an aquarium on the patients’ blood pressure, heart rate, anxiety, or mood.

BackgroundProton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs.MethodsAmong patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013–2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke.ResultsDuring a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65–0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation.ConclusionIn patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

The British colony of South Australia, established in 1836, offered a fresh start to migrants hoping for a better life. A cohort of settlers buried in a section of St Mary’s Anglican Church Cemetery (1847–1927) allocated for government funded burials was investigated to determine their health, with a focus on skeletal manifestations associated with metabolic deficiencies. Findings of St Mary’s sample were compared with those published for contemporary skeletal samples from two British cemeteries, St Martin’s, Birmingham, and St Peter’s, Wolverhampton, to explore similarities and differences. To investigate the changing economic background of the St Mary’s cohort, which may have influenced the location of their burial within the cemetery, the number and demographic profile of government funded burials and those in privately funded leased plots were compared. The study sample consisted of the skeletal remains of 65 individuals (20 adults, 45 subadults) from St Mary’s Cemetery ‘free ground’ section. The bones and teeth of individuals in this cohort showed evidence of pathological manifestations, including areas of abnormal porosity in bone cortices in 9 adults and 12 subadults and flaring of metaphyses (one subadult) and costochondral junctions of the ribs (one subadult). Porous lesions of orbital roof bones (Types 3 to 4) were seen on three subadults. Macroscopic examination of teeth identified enamel hypoplastic defects and micro-CT scans showed areas of interglobular dentine. Comparison of St Mary’s findings with the British samples revealed that prevalences of manifestations associated with vitamin C deficiency were higher at St Mary’s and manifestations associated with vitamin D deficiency were lower respectively. The location of burial pattern at St Mary’s Cemetery, from the mid-1840s to1860s, showed differences in the economic status of migrants. This pattern changed from the 1870s, which reflected improvements in the local economy and the economic recovery of the colony.

This paper reports survey findings on the Swiss public’s willingness, attitudes, and concerns regarding personalized health research participation by providing health information and biological material. The survey reached a sample of 15,106 Swiss residents, from which we received 5,156 responses (34.1% response rate). The majority of respondents were aware of research using human biological samples (71.0%) and held a positive opinion towards this type of research (62.4%). Of all respondents, 53.6% indicated that they would be willing to participate in a personalized health research project. Willingness to participate was higher in younger, higher educated, non-religious respondents with a background in the health sector. Respondents were more willing to provide ‘traditional’ types of health data, such as health questionnaires, blood or biological samples, as opposed to social media or app-related data. All respondents valued the return of individual research results, including risk for diseases for which no treatment is available. Our findings highlight that alongside general positive attitudes towards personalized health research using data and samples, respondents have concerns about data privacy and re-use. Concerns included potential discrimination, confidentiality breaches, and misuse of data for commercial or marketing purposes. The findings of this large-scale survey can inform Swiss research institutions and assist policymakers with adjusting practices and developing policies to better meet the needs and preferences of the public. Efforts in this direction could focus on research initiatives engaging in transparent communication, education, and engagement activities, to increase public understanding and insight into data sharing activities, and ultimately strengthen personalized health research efforts., PLoS ONE, 16 (4), ISSN:1932-6203

Computational modeling of electrophysiological properties of the rabbit heart is a commonly used way to enhance and/or complement findings from classic lab work on single cell or tissue levels. Yet, thus far, there was no possibility to extend the scope to include the resulting body surface potentials as a way of validation or to investigate the effect of certain pathologies. Based on CT imaging, we developed the first openly available computational geometrical model not only of the whole heart but also the complete torso of the rabbit. Additionally, we fabricated a 32-lead ECG-vest to record body surface potential signals of the aforementioned rabbit. Based on the developed geometrical model and the measured signals, we then optimized the activation sequence of the ventricles, recreating the functionality of the Purkinje network, and we investigated different apico-basal and transmural gradients in action potential duration. Optimization of the activation sequence resulted in an average root mean square error between measured and simulated signal of 0.074 mV/ms for all leads. The best-fit T-Wave, compared to measured data (0.038 mV/ms), resulted from incorporating an action potential duration gradient from base to apex with a respective shortening of 20 ms and a transmural gradient with a shortening of 15 ms from endocardium to epicardium. By making our model and measured data openly available, we hope to give other researchers the opportunity to verify their research, as well as to create the possibility to investigate the impact of electrophysiological alterations on body surface signals for translational research.

Aims of the study Thrombopoietin receptor agonists (TPO-RAs) are approved for immune thrombocytopenia (ITP), but their impact on health-related quality of life (HRQoL) remains poorly investigated in clinical practice. This observational study aimed to gain insight into real-world patient-reported experiences of the burden of ITP and TPO-RAs. Method An online questionnaire of closed questions was used to collect views of patients with primary ITP from Switzerland, Austria, and Belgium, between September 2018 and April 2020. Results Of 46 patients who completed the questionnaire (total cohort), 41% were receiving TPO-RAs. A numerically higher proportion of patients reported being free from symptoms at the time of the questionnaire (54%) than at diagnosis (24%), irrespective of treatment type. Bleeding, the most frequently reported symptom at diagnosis (59%), was reduced at the time of the questionnaire (7%). Conversely, fatigue was reported by approximately 40% of patients at both diagnosis and the time of the questionnaire. Having a normal life and their disease under control was reported by 83% and 76%, respectively, but 41% were worried/anxious about their condition. Nearly 50% reported that ITP impaired their engagement in hobbies/sport or energy levels and 63% reported no impact on employment. When stratified by TPO-RA use, bleeding was better controlled in those receiving TPO-RAs than not (0% vs 11%). A numerically lower proportion receiving TPO-RAs than not reported worry/anxiety about their condition (16% vs 59%) and shifting from full-time to part-time employment (11% vs 22%). Similar proportions were satisfied with their therapy whether they were receiving TPO-RAs or not (89% vs 85%). Conclusions Many factors affect HRQoL in patients with ITP. Of patients receiving TPO-RAs, none experienced bleeding at the time of the questionnaire; they also showed a more positive perspective for some outcomes than those not using TPO-RAs. However, fatigue was not reduced by any treatment.

Background Neonatal mortality in Guinea accounts for about 30% of all fatalities in children younger than five years. Countrywide, specialized neonatal intensive care is provided in one single clinic with markedly limited resources. To implement targeted measures, prospective data on patient characteristics and factors of neonatal death are needed. Objective To determine the rates of morbidity and mortality, to describe clinical characteristics of admitted newborns requiring intensive care, to assess the quality of disease management, and to identify factors contributing to neonatal mortality. Methods Prospective observational cohort study of newborns admitted to the hospital between mid-February and mid-March 2019 after birth in other institutions. Data were collected on maternal/prenatal history, delivery, and in-hospital care via convenience sampling. Associations of patient characteristics with in-hospital death were assessed using cause-specific Cox proportional-hazards models. Results Half of the 168 admitted newborns underwent postnatal cardiopulmonary resuscitation. Reasons for admission included respiratory distress (49.4%), poor postnatal adaptation (45.8%), prematurity (46.2%), and infections (37.1%). 101 newborns (61.2%) arrived in serious/critical general condition; 90 children (53.9%) showed clinical signs of neurological damage. Quality of care was poor: Only 59.4% of the 64 newborns admitted with hypothermia were externally heated; likewise, 57.1% of 45 jaundiced infants did not receive phototherapy. Death occurred in 56 children (33.3%) due to birth asphyxia (42.9%), prematurity (33.9%), and sepsis (12.5%). Newborns in serious/critical general condition at admission had about a fivefold higher hazard to die than those admitted in good condition (HR 5.21 95%-CI 2.42–11.25, p = Conclusion Neonatal mortality was strikingly high. Birth asphyxia, prematurity, and infection accounted for 89.3% of death, aggravated by poor quality of in-hospital care. Children with serious general condition at admission had poor chances of survival. The whole concept of perinatal care in Guinea requires reconsideration.

The key to evolution is reproduction. Pathogens can either kill the human host or can invade the host without causing death, thus ensuring their own survival, reproduction and spread. Tuberculosis, treponematoses and leprosy are widespread chronic infectious diseases whereby the host is not immediately killed. These diseases are examples of the co-evolution of host and pathogen. They can be well studied as the paleopathological record is extensive, spanning over 200 human generations. The paleopathology of each disease has been well documented in the form of published synthetic analyses recording each known case and case frequencies in the samples they were derived from. Here the data from these synthetic analyses were re-analysed to show changes in the prevalence of each disease over time. A total of 69,379 skeletons are included in this study. There was ultimately a decline in the prevalence of each disease over time, this decline was statistically significant (Chi-squared, p

RationaleThe COVID-19 pandemic induces considerable strain on intensive care unit resources.ObjectivesWe aim to provide early predictions of individual patients’ intensive care unit length of stay, which might improve resource allocation and patient care during the on-going pandemic.MethodsWe developed a new semiparametric distributional index model depending on covariates which are available within 24h after intensive care unit admission. The model was trained on a large cohort of acute respiratory distress syndrome patients out of the Minimal Dataset of the Swiss Society of Intensive Care Medicine. Then, we predict individual length of stay of patients in the RISC-19-ICU registry.MeasurementsThe RISC-19-ICU Investigators for Switzerland collected data of 557 critically ill patients with COVID-19.Main ResultsThe model gives probabilistically and marginally calibrated predictions which are more informative than the empirical length of stay distribution of the training data. However, marginal calibration was worse after approximately 20 days in the whole cohort and in different subgroups. Long staying COVID-19 patients have shorter length of stay than regular acute respiratory distress syndrome patients. We found differences in LoS with respect to age categories and gender but not in regions of Switzerland with different stress of intensive care unit resources.ConclusionA new probabilistic model permits calibrated and informative probabilistic prediction of LoS of individual patients with COVID-19. Long staying patients could be discovered early. The model may be the basis to simulate stochastic models for bed occupation in intensive care units under different casemix scenarios.

Introduction Polytrauma and traumatic brain injury (TBI) patients are among the most vulnerable patients in trauma care and exhibit increased morbidity and mortality. Timely care is essential for their outcome. Severe TBI with initially high scores on the Glasgow Coma (GCS) scores is difficult to recognise on scene and referral to a Major Trauma Center (MTC) might be delayed. Therefore, we examined current referral practice, injury patterns and mortality in these patients. Materials and methods Retrospective, nationwide cohort study with Swiss Trauma Register (STR) data between 01/012015 and 31/12/2018. STR includes patients ≥16 years with an Injury Severity Score (ISS) >15 and/or an Abbreviated Injury Scale (AIS) for head >2. We performed Cox proportional hazard models with injury type as the primary outcome and mortality as the dependent variable. Secondary outcomes were inter-hospital transfer and age. Results 9,595 patients were included. Mortality was 12%. 2,800 patients suffered from isolated TBI. 69% were men. Median age was 61 years and median ISS 21. Two thirds of TBI patients had a GCS of 13–15 on admission to the Emergency Department (ED). 26% of patients were secondarily transferred to an MTC. Patients with isolated TBI and those aged ≥65 years were transferred more often. Crude analysis showed a significantly elevated hazard for death of 1.48 (95%CI 1.28–1.70) for polytrauma patients with severe TBI and a hazard ratio (HR) of 1.82 (95%CI 1.58–2.09) for isolated severe TBI, compared to polytrauma patients without TBI. Patients directly admitted to the MTC had a significantly elevated HR for death of 1.63 (95%CI 1.40–1.89), compared to those with secondary transfer. Conclusions A high initial GCS does not exclude the presence of severe TBI and triage to an MTC should be seriously considered for elderly TBI patients.

Facial appearance expresses numerous cues about physical qualities as well as psychosocial and personality traits. Attractive faces are recognized clearly when seen and are often viewed advantageously in professional, social and romantic relationships. On the other hand, self-perceived attractiveness is not well understood and has been mainly attributed to psychological and cognitive factors. Here we use 3-dimensional facial surface data of a large young adult population (n = 601) to thoroughly assess the effect of facial shape on self-perceived facial attractiveness. Our results show that facial shape had a measurable effect on self-perception of facial attractiveness in both sexes. In females, self-perceived facial attractiveness was linked to decreased facial width, fuller anterior part of the lower facial third and more pronounced middle forehead and root of the nose. Males favored a well-defined chin, flatter cheeks and zygomas, and more pronounced eyebrow ridges, nose and middle forehead. The findings of this study support the notion that self-perceived facial attractiveness is not only motivated by psychological traits, but objectively measured phenotypic traits also contribute significantly. The role of social stereotypes for facial attractiveness in modern society is also inferred and discussed.

SARS-CoV-2 has clearly shown that efficient management of infectious diseases requires a top-down approach which must be complemented with a bottom-up response to be effective. Here we investigate a novel approach to surveillance for transboundary animal diseases using African Swine (ASF) fever as a model. We collected data both at a population level and at the local level on information-seeking behavior respectively through digital data and targeted questionnaire-based surveys to relevant stakeholders such as pig farmers and veterinary authorities. Our study shows how information-seeking behavior and resulting public attention during an epidemic, can be identified through novel data streams from digital platforms such as Wikipedia. Leveraging attention in a critical moment can be key to providing the correct information at the right moment, especially to an interested cohort of people. We also bring evidence on how field surveys aimed at local workers and veterinary authorities remain a crucial tool to assess more in-depth preparedness and awareness among front-line actors. We conclude that these two tools should be used in combination to maximize the outcome of surveillance and prevention activities for selected transboundary animal diseases such as ASF.

The cortical bone trajectory (CBT) has been introduced with the aim of better screw hold, however, screw-rod constructs with this trajectory might provide less rigidity in lateral bending (LB) and axial rotation (AR) compared to the constructs with the traditional trajectory (TT). Therefore, the addition of a horizontal cross-connector could be beneficial in counteracting this possible inferiority. The aim of this study was to compare the primary rigidity of TT with CBT screw-rod constructs and to quantify the effect of cross-connector-augmentation in both. Spines of four human cadavers (T9 –L5) were cropped into 15 functional spine units (FSU). Eight FSUs were instrumented with TT and seven FSUs with CBT pedicle screws. The segments were tested in six loading directions in three configurations: uninstrumented, instrumented with and without cross-connector. The motion between the cranial and caudal vertebra was recorded. The range of motion (ROM) between the CBT and the TT group did not differ significantly in either configuration. Cross-connector -augmentation did reduce the ROM in AR (16.3%, 0.27°, p = 0.02), LB (2.9%, 0.07°, p = 0.03) and flexion-extension FE (2.3%, 0.04°, p = 0.02) for the TT group and in AR (20.6%, 0.31°, p = 0.01) for the CBT-group. The primary rigidity of TT and CBT single level screw-rod constructs did not show significant difference. The minimal reduction of ROM due to cross-connector-augmentation seems clinically not relevant. Based on the findings of these study there is no increased necessity to use a cross-connector in a CBT-construct., PLoS ONE, 16 (6), ISSN:1932-6203

BackgroundThe effect of vegan diets on metabolic processes in the body is still controversial in ultra endurance athletes. The study aims to determine gut microbiome adaptation to extreme exercise according to vegan or omnivore diet consumed in ultra-marathoners. We also seek to evaluate long-term vegan diets’ effects on redox homeostasis, and muscle fatigue, and assess energy availability.MethodsSeventy participants will be assigned to the study, including 35 vegan ultra-marathoners and 35 omnivores competing in the Sri-Chinmoy ultra marathon race. Research data will be collected from the participants at four steps (three visits to the research laboratory and the race day) throughout the study. At the first visit (seven days before the race), fecal samples, and anthropometric measurements will be collected. Body composition will be measured using DXA. Participants will be informed about keeping detailed food records and will be asked to record their diet data and activity logs during the entire study period. At second visit, maximum oxygen consumption will be measured on treadmill. On race day, blood samples will be collected immediately before, and 0. min, 2 hours, and 24 hours after the race. Body weight will be measured before and after the race. The blood and fecal samples will be stored at -80 C until analysis. Plasma malondialdehyde, reactive oxygen metabolites, total antioxidant capacity, Heatshockprotein-70, and serum Orosomucoid-1 will be analyzed in blood samples. Fecal samples will be analyzed with shotgun metagenomic analysis and interpreted using bioinformatics pipeline (HumanN2). Statistical tests will be analyzed using SPSS version 23.0 and R Software.DiscussionStudy findings will determine the effects of the vegan diet on sports performance, revealing the multiple interactions between host and gut microbiome at the whole metagenomic level. Additionally, results will show the possible adaptation throughout the race by analyzing blood and fecal samples. Furthermore, by assessing energy availability and determining host-metabolite crosstalk for ultra-endurance athletes, possible nutritional deficiencies can be identified. Thus, advanced nutritional strategies can be developed based on metabolic needs.Trial registrationCurrent controlled trials, ISRCTN registry 69541705. Registered on 8 December 2019.

In this paper we analyze panel data (N = 400) to investigate the change in attitudes towards the Covid-19 measures and the change in compliance behavior between the first and second lockdowns in a sample of young adults from the University of Bern, Switzerland. We find considerable fatigue. While respondents expressed high acceptance of and compliance with the Covid-19 measures during the first lockdown, both acceptance and compliance behavior decreased substantially during the second lockdown. Moreover, we show via a structural equation model that respondents’ compliance behavior is largely driven by the perception of how others behave and by the acceptance of the Covid-19 measures. All other effects scrutinized e.g., individual and social risk perception, trust in politics, and pro-social orientations affect compliance behavior via the acceptance of Covid-19 measures. We also conduct two tests of causality of the estimated relation between attitudes towards the measures and social distancing behavior. The first test incorporates the effect of compliance behavior reported during the first lockdown on attitudes during the second lockdown. The second test involves estimating a first difference panel regression model of attitudes on compliance behavior. The results of both tests suggest that the effect of Covid-19 attitudes on social distancing behavior can be interpreted causally.

Background Apoptotic pathways in platelets are important for their survival and function. Platelet apoptosis may be involved in the pathogenesis of immune thrombocytopenia (ITP), an autoimmune-mediated disease. In contrast to the intrinsic apoptosis pathway, not much is known about the extrinsic pathway mechanisms in platelets. Objectives To investigate the expression of proteins involved in the extrinsic apoptosis pathway, including the death receptors, adaptor and regulator proteins in human platelets. To determine a possible trigger of the extrinsic apoptosis pathway in platelets. Methods To investigate the expression of key markers of the extrinsic pathway we used targeted immunofluorescence and flow cytometry assays. To study their expression and interaction we performed Western blotting and co-immunoprecipitation. Treated platelets with different apoptosis triggers were subjected to flow cytometry. Results We could identify the protein expression of the pro-apoptotic proteins TRADD (Tumor Necrosis Factor Receptor type 1- Associated DEATH Domain protein), TRAF2/5, (TNF Associated Factor) and DEDAF (Death Effector Domain- Associated Factor), FADD (Fas-Associated protein with death domain) as well as the anti-apoptotic proteins DJ-1 (Deglycase 1) and c-FLIP in human platelets. ABT-737 treatment induced a disruption in the co-localization of DJ-1 with FADD. Platelets treated with ABT-737 showed an activation in caspase-3 and -8. The exposure to TNF (Tumor Necrosis Factor), FasL (Fas ligand), and TWEAK or to plasma derived from ITP patients, did not lead to changes in caspase-3 and -8 activation in platelets. Conclusions Human platelets express some proteins of the extrinsic apoptosis pathway which can be modulated only by ABT-737 treatment. However so far, no other apoptosis trigger or interaction with an external receptor have been yet identified.

Background We have recently reported reduced physical activity (PA) in people with cystic fibrosis (pwCF) with and without lung transplantation (LTX) during a 6-week stringent lockdown in Switzerland. This follow-up study explores the impact of coronavirus-2019 disease (COVID-19) related pandemic restrictions on individuals’ therapy regimens and health-related aspects in pwCF. Methods We conducted a cross-sectional web-based national survey in Spring 2021. The survey included questions on daily PA, airway clearance and inhalation therapy, questions on COVID-19-compatible symptoms, diagnostic tests and vaccination status, and enquired health-related aspects covering the pandemic period between March 2020 to April 2021. Results 193 individuals with CF (53% female; 25% LTX recipients) participated. Among pwCF, 10 reported COVID-19 (n = 2 LTX recipients), two subjects were hospitalized, no invasive ventilation required, no deaths. The clinical course was generally mild. Overall, 46% reported less PA during the pandemic, mostly due to closed fitness facilities (85%), lack of motivation (34%), and changes in daily structures (21%). In contrast, 32/193 (17%) pwCF were able to increase their PA levels: 12 (38%) and 11 (34%) reported undertaking home-based training and outdoor activities more frequently; 6 (19%) reported an increase in routine PA, and another 3 (9%) started new activities. Among pwCF without LTX, 5% and 4% reported to undertake less airway clearance and inhalation therapy, respectively. Conclusions Our study reveals unfavorable consequences of COVID-19 pandemic restrictions on PA of pwCF with unknown long-term consequences for their overall physical fitness and lung health. Strategies to overcome this undesirable situation are needed; increased uptake of telehealth PA programs and virtual exercise classes to promote PA participation might be one promising approach along with vaccination of pwCF and their close contacts.

The cellular prion protein (PrP) is essential to the long-term maintenance of myelin sheaths in peripheral nerves. PrP activates the adhesion G-protein coupled receptor Adgrg6 on Schwann cells and initiates a pro-myelination cascade of molecular signals. Because Adgrg6 is crucial for peripheral myelin development and regeneration after nerve injury, we investigated the role of PrP in peripheral nerve repair. We performed experimental sciatic nerve crush injuries in co-isogenic wild-type and PrP-deficient mice, and examined peripheral nerve repair processes. Generation of repair Schwann cells, macrophage recruitment and remyelination were similar in PrP-deficient and wild-type mice. We conclude that PrP is dispensable for sciatic nerve de- and remyelination after crush injury. Adgrg6 may sustain its function in peripheral nerve repair independently of its activation by PrP.

Objectives To assess the feasibility of radiologic measurements and find out whether hearing outcome could be predicted based on computer tomography (CT) scan evaluation in patients with temporal bone fractures and suspected ossicular joint dislocation. Methods We assessed 4002 temporal bone CT scans and identified 34 patients with reported ossicular joint dislocation due to trauma. We excluded those with no proven traumatic ossicular dislocation in CT scan and patients with bilateral temporal bone fractures. We measured four parameters such as malleus-incus axis distance, malleus-incus angle at midpoints, malleus- incus axis angle and ossicular joint space. The contralateral healthy side served as its own control. Hearing outcome 1–3 months after the index visit was analyzed. We assessed diagnostic accuracy and performed a logistic regression using radiologic measurement parameters for outcome prediction of conductive hearing loss (defined as >20dB air-bone gap). Results We found excellent inter-rater agreement on the measurement of axis deviation between incus and malleus in CT scans (interclass correlation coefficient 0.81). The larger the deviation of incus and malleus axis, the higher probability of poor hearing outcome (odds ratio (OR) 2.67 per 0.1mm, p = .006). A cut-off value for the axis deviation of 0.25mm showed a sensitivity of 0.778 and a specificity of 0.94 (p < .001) for discrimination between poor and good hearing outcome in terms of conductive hearing loss. Conclusion Adequate assessment of high resolution CT scans of temporal bone in which ossicular chain dislocation had occurred after trauma was feasible. Axis deviations of the incus and the malleus were strongly predictive for poor hearing outcome in terms of air conduction 1–3 months after trauma. We propose a 3-level classification system for hearing outcome prediction based on radiologic measures.

Background Chronic Chagas Cardiomyopathy (CCM) is a unique form of cardiomyopathy compared to other etiologies of heart failure. In CCM, risk prediction based on biomarkers has not been well-studied. We assessed the prognostic value of a biomarker panel to predict a composite outcome (CO), including the need for heart transplantation, use of left ventricular assist devices, and mortality. Methods Prospective cohort study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Survival analyses were performed using Cox proportional hazard models. Results During a median follow-up of 52 months, the mortality rate was 20%, while the CO was observed in 25% of the patients. Four biomarkers (NT-proBNP, hs-cTnT, sST2, and Cys-C) were associated with the CO; concentrations of NT-proBNP and hs-cTnT were associated with the highest AUC (85.1 and 85.8, respectively). Combining these two biomarkers above their selected cut-off values significantly increased risk for the CO (HR 3.18; 95%CI 1.31–7.79). No events were reported in the patients in whom the two biomarkers were under the cut-off values, and when both levels were above cut-off values, the CO was observed in 60.71%. Conclusion The combination of NT-proBNP and hs-TnT above their selected cut-off values is associated with a 3-fold increase in the risk of the composite outcome among CCM patients. The use of cardiac biomarkers may improve prognostic evaluation of patients with CCM.

Objective We aimed 1) to test the applicability of the previously suggested prognostic value of CPET to elderly cardiac rehabilitation patients and 2) to explore the underlying mechanism of the greater improvement in exercise capacity (peak oxygen consumption, VO2) after CR in surgical compared to non-surgical cardiac patients. Methods Elderly patients (≥65 years) commencing CR after coronary artery bypass grafting, surgical valve replacement (surgery-group), percutaneous coronary intervention, percutaneous valve replacement or without revascularisation (non-surgery group) were included in the prospective multi-center EU-CaRE study. CPETs were performed at start of CR, end of CR and 1-year-follow-up. Logistic models and receiver operating characteristics were used to determine prognostic values of CPET parameters for major adverse cardiac events (MACE). Linear models were performed for change in peak VO2 (start to follow-up) and parameters accounting for the difference between surgery and non-surgery patients were sought. Results 1421 out of 1633 EU-CaRE patients performed a valid CPET at start of CR (age 73±5.4, 81% male). No CPET parameter further improved the receiver operation characteristics significantly beyond the model with only clinical parameters. The higher improvement in peak VO2 (25% vs. 7%) in the surgical group disappeared when adjusted for changes in peak tidal volume and haemoglobin. Conclusion CPET did not improve the prediction of MACE in elderly CR patients. The higher improvement of exercise capacity in surgery patients was mainly driven by restoration of haemoglobin levels and improvement in respiratory function after sternotomy. Trial registration Netherlands Trial Register, Trial NL5166.

Pulmonary acini represent the functional gas-exchanging units of the lung and are defined as the airways distal of the terminal bronchioles. Due to technical limitations, it was not possible to identify individual acini on microscopic lung sections. Recently, X-ray tomographic microscopy has been adapted to lung imaging to overcome these limitations. This study aimed to follow the acinar development and to gain insight into changes of the acinar structures during postnatal development. Rat lungs were fixed by instillation at postnatal days P4, P10, P21, and P60. Right lower lobes were imaged at the TOMCAT beamline of the Swiss Light Source synchrotron facility at a voxel size of 1.48 μ m. Individual acini were segmented out of the obtained 3D data sets by closing the airways at the acinar entrance which is the transition point from conducting to gas exchanging airways happens. Acinar development was followed by estimating the individual acinar volume, complexity, and number of alveoli (N=268). We observed that the mean volume of the acini increases 10 times between days 4 and 60 which corresponds to a 10 times increase of the total lung volume. During the same time, the coefficients of variation dropped from 1.26 to 0.49 and the difference between the mean volumes of the fraction of the 20 % smallest and 20 % largest acini decreased from a factor of 27.26 (day 4) to a factor of 4.07 (day 60). This indicates that the dispersion of the value is based on an entirely different pattern of distribution of acinar sizes. Methodologically, we conclude that our approach is well suited to follow acinar development and to acquire large amounts of data comparable to classical stereology in a time-efficient manner. Biologically, we conclude that the newly formed acini show a large size distribution which is reduced by a factor of 7 until adulthood. Most likely the latter leads to a more homogeneous ventilation of the lung.

The health risk of the coronavirus pandemic is age-specific. The symptoms of a COVID-19 infection are usually mild in the healthy population below the age of 65; however, the measures laid down to prevent the spread of the virus apply typically to the whole population. Hence, those who have a low risk of severe symptoms face a social dilemma in cooperating and complying with the safety measures: Cooperating in preventing the spread of the disease is good for society but comes with individual costs. These costs provide an incentive not to cooperate with the safety measures. In this paper we analyze via structural equation modelling a sample of young adults (N = 510) who were surveyed right after the end of the first lockdown period in Switzerland. We investigate why and to what extent they cooperated in preventing the epidemic by following the recommendation to stay at home as much as possible. We hypothesize that those respondents who perceive themselves to be personally at risk, or who have relatives belonging to the risk group, complied more often with the safety measures as compared to those without severe risks. Cooperating should also be linked to individuals’ pro-social orientation. Furthermore, we hypothesize that those who believe that the virus is dangerous for society or who have a personal interest in protection show higher support for the general safety measures. Our empirical results show that compliance with the coronavirus social distancing measures was generally very high during the first lockdown. Although young adults perceived themselves to be at low personal risk, they still believed that the virus is dangerous for society. Those who had a personal interest in staying at home because they had relatives belonging to the risk group complied more often with the safety measures. Overall, the results suggest that the support of the preventive measures is the most important promoter of cooperation to prevent the spread of COVID-19.

Objective Postoperative acute kidney injury (po-AKI) is frequently observed after major vascular surgery and impacts on mortality rates. Early identification of po-AKI patients using the novel urinary biomarkers insulin-like growth factor-binding-protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) might help in early identification of individuals at risk of AKI and enable timely introduction of preventative or therapeutic interventions with the aim of reducing the incidence of po-AKI. We investigated whether biomarker-based monitoring would allow for early detection of po-AKI in patients undergoing abdominal aortic interventions. Methods In an investigator-initiated prospective single-center observational study in a tertiary care academic center, adult patients with emergency/ elective abdominal aortic repair were included. Patients were tested for concentrations of urinary (TIMP-2) x (IGFBP7) at baseline, after surgical interventions (PO), and in the mornings of the first postoperative day (POD1). The primary endpoint was a difference in urinary (TIMP-2) x (IGFBP7) levels at POD1 in patients with/ without po-AKI (all KDIGO stages, po-AKI until seven days after surgery). Secondary endpoints included sensitivity/ specificity analyses of previously proposed cut-off levels and clinical outcome measures (e.g. need for renal replacement therapy). Results 93 patients (n = 71 open surgery) were included. Po-AKI was observed in 33% (31/93) of patients. Urinary (TIMP-2) x (IGFBP7) levels at POD1 did not differ between patients with/ without AKI (median 0.39, interquartile range [IQR] 0.13–1.05 and median 0.23, IQR 0.14–0.53, p = .11, respectively) and PO (median 0.2, IQR 0.08–0.42, 0.18, IQR 0.09–0.46; p = .79). Higher median (TIMP-2) x (IGFBP7) levels were noted in KDIGO stage 3 pAKI patients at POD1 (3.75, IQR 1.97–6.92; p = .003). Previously proposed cutoff levels (0.3, 2) showed moderate sensitivity/ specificity (0.58/0.58 and 0.16/0.98, respectively). Conclusion In a prospective monocentric observational study in patients after abdominal aortic repair, early assessment of urinary (TIMP-2) x (IGFBP7) did not appear to have adequate sensitivity/ specificity to identify patients that later developed postoperative AKI. Clinicaltrials.gov NCT03469765, registered March 19, 2018.