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Large-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows. This includes extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUSs) are a challenge to personalized medicine. This challenge is further compounded by the complexity and heterogeneity of the standards used to describe genetic variants and the associated phenotypes when searching for relevant information to support clinical decision making. To address this, all five Swiss academic institutions for Medical Genetics joined forces with the Swiss Institute of Bioinformatics (SIB) to create SwissGenVar as a user-friendly nationwide repository and sharing platform for genetic variant data generated during routine diagnostic procedures and research sequencing projects. Its aim is to provide a protected environment for expert evidence sharing about individual variants to harmonize and upscale their significance interpretation at the clinical grade according to international standards. To corroborate the clinical assessment, the variant-related data will be combined with consented high-quality clinical information. Broader visibility will be achieved by interfacing with international databases, thus supporting global initiatives in personalized healthcare. [ABSTRACT FROM AUTHOR]

Introduction/objectives: The ASCORE study on treatment for rheumatoid arthritis (RA) showed better retention and clinical response rates for abatacept as first-line versus later-line therapy. This post hoc analysis of ASCORE assessed 2-year retention, efficacy, and safety of subcutaneous (SC) abatacept in Germany, Austria, and Switzerland. Methods: Adults with RA who initiated SC abatacept 125 mg once weekly were assessed. Primary endpoint was abatacept retention rate at 2 years. Secondary endpoints: proportions of patients with low disease activity (LDA)/remission per Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (≤ 3.2), Simplified Disease Activity Index (≤ 11), and Clinical Disease Activity Index (≤ 10). Outcomes were analyzed by treatment line and serostatus. Results: For the pooled cohort, the 2-year abatacept retention rate was 47.6%; retention was highest in biologic-naïve patients (50.5% [95% confidence interval 44.9, 55.9]). Patients seropositive for both anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF; + / +) at baseline had a higher 2-year abatacept retention rate than patients with single seropositivity for either APCA or RF or double-seronegativity (− / −), irrespective of treatment line. At 2 years, a higher proportion of patients who were biologic-naïve were in LDA/remission than patients with one or ≥ two prior biologics. Conclusion: A higher proportion of patients with + / + RA (compared with − / − RA) had abatacept retention after 2 years. Early identification of patients with seropositive RA may facilitate a precision-medicine approach to RA treatment, leading to a higher proportion of patients in LDA/remission. Trial registration number: NCT02090556; date registered: March 18, 2014 (retrospectively registered). Key Points • This post hoc analysis of a German-speaking subset of European patients with RA from the global ASCORE study (NCT02090556) showed that retention of SC abatacept within this subset was 47.6%, with good clinical outcomes after 2 years. • Patients with double-seropositive RA (ACPA and RF positive) had higher retention of abatacept than patients with double-seronegative RA (ACPA and RF negative). Retention and clinical responses were highest for patients who were biologic-naïve compared with patients who had one or ≥ two prior biologic treatments. • These real-world data may be useful for clinicians in informing individualized treatment pathways for patients with RA, and fostering superior disease control and clinical outcomes. [ABSTRACT FROM AUTHOR]

Despite decreased numbers of sexual partners, the COVID-19 pandemic had limited impact on the prevalence of attending private sex parties, traveling for sex within Switzerland, and practicing chemsex in men with HIV who have sex with men. COVID-19 risk perception was low, and STI-diagnosis incidence rates remained stable over time. [ABSTRACT FROM AUTHOR]

Background: Despite effective prevention approaches, ongoing HIV-1 transmission remains a public health concern indicating a need for identifying its drivers.Methods: We combine a network-based clustering method using evolutionary distances between viral sequences with statistical learning approaches to investigate the dynamics of HIV-1 transmission in the Swiss HIV Cohort Study and to predict the drivers of ongoing transmission.Results: We find that only a minority of clusters and patients acquire links to new infections between 2007 and 2020. While the growth of clusters and the probability of individual patients acquiring new links in the transmission network was associated with epidemiological, behavioral and virological predictors, the strength of these associations decreased substantially when adjusting for network characteristics. Thus, these network characteristics can capture major heterogeneities beyond classical epidemiological parameters. When modeling the probability of a newly diagnosed patient being linked with future infections, we found that the best predictive performance (median AUCROC = 0.77) was achieved by models including characteristics of the network as predictors and that models excluding them performed substantially worse (median AUCROC = 0.54).Conclusions: These results highlight the utility of molecular epidemiology-based network approaches for analysing and predicting ongoing HIV-1-transmission dynamics. This approach may serve for real-time prospective assessment of HIV-1-transmission. [ABSTRACT FROM AUTHOR]

In the Swiss HIV Cohort Study, 61 of 222 (27%) HIV–suppressed persons with chronic hepatitis B virus (HBV) infection had HBV replication after 2 years on tenofovir, of whom 77% were suppressed thereafter. Self-reported adherence to therapy and HBV viral load at tenofovir initiation were predictors of persistent replication. [ABSTRACT FROM AUTHOR]

While there is broad evidence to suggest that individual stress increases, and that high couple relationship quality reduces the risk for psychological distress, our understanding of these associations in couples dealing with infertility remains limited. In this cross-sectional study, we used dyadic data-analysis (Actor-Partner Interdependence Model; APIM) to examine the effects of infertility-related distress (experienced as an individual risk factor) and couple relationship quality (experienced as a couple-based resource), on psychological distress in a sample of 116 infertile couples. 59% of women and 23% of men reported clinical levels of psychological distress, 71% of women and 45% of men reported infertility-related distress, and 3% of participants reported low couple relationship quality. Infertility-related distress predicted psychological distress at the individual level ('actor effects') while men's infertility-related distress predicted women's psychological distress (partner effect'). Women without medically assisted reproduction (MAR) treatment exposure reported significantly higher couple relationship quality than women with MAR exposure, and men without treatment exposure reported significantly lower infertility-related distress than men with exposure. The level of psychological distress depended on whether both or neither of the partners, or only one partner reported infertility-related distress. Couple relationship quality was not associated with distress, which may imply that dyadic dimensions other than overall satisfaction could be relevant in supporting couples facing infertility. [ABSTRACT FROM AUTHOR]

Introduction: In 2018, Switzerland changed its guidelines to support women living with HIV wishing to breastfeed. The exposure of antiretroviral drugs (ARVs) in breastmilk and the ingested daily dose by the breastfed infant are understudied, notably for newer ARVs. This study aimed to quantify ARV concentrations in maternal plasma and breastmilk to determine the milk/plasma ratio, to estimate daily infant ARV dose from breastfeeding and to measure ARV concentrations in infants.Methods: All women wishing to breastfeed were included, regardless of their ARV treatment. Breastmilk and maternal plasma samples were mostly collected at mid-dosing interval.Results: Twenty-one mother/child pairs were enrolled; of those several were on newer ARVs including 10 raltegravir, 1 bictegravir, 2 rilpivirine, 2 darunavir/ritonavir and 3 tenofovir alafenamide. No vertical HIV transmission was detected (one infant still breastfed). The median milk/plasma ratios were 0.96/0.39 for raltegravir once/twice daily, 0.01 for bictegravir, 1.08 for rilpivirine, 0.12 for darunavir/ritonavir and 4.09 for tenofovir alafenamide. The median estimated infant daily dose (mg/kg) from breastfeeding was 0.02/0.25 for raltegravir once/twice daily, 0.01 for bictegravir, 0.02 for rilpivirine, 0.05 for darunavir/ritonavir and 0.007 for tenofovir alafenamide, resulting in relative infant dose <10% exposure index for all ARVs.Conclusions: ARVs were transferred to a variable extent in breastmilk. Nevertheless, the estimated daily ARV dose from breastfeeding remained low. Differential ARV exposure was observed in breastfed infants with some ARVs being below/above their effective concentrations raising the concern of resistance development if HIV infection occurs. More data on this potential risk are warranted to better support breastfeeding. [ABSTRACT FROM AUTHOR]

Objective: In face of disparities in access to cancer care, it has been proposed to measure accessibility and to explore policy strategies for mitigating inequality of access. We aimed to determine the accessibility of Swiss paediatric oncology centres. Methods: We employed spatial accessibility analysis, calculating driving time to nearest facility. Four data types were used: disaggregated population data, administrative data, street network data and addresses of centres. Besides analysing general accessibility, we compared access of urban versus rural areas and of Swiss citizens versus foreign residents and evaluated designating a new centre to improve accessibility. Results: Overall, 97.4% could reach the nearest centre within 120 min (95.0% < 90 min, 86.5% < 60 min, 48.5% < 30 min). Accessibility could most effectively be improved by a new centre in Sion (city in the southwest of Switzerland). Access in urban areas was better than in rural areas. In urban areas, access of European Union/European Free Trade Association (EU/EFTA) and non‐European residents was better than access of Swiss citizens and residents from non‐EU European countries. Conclusion: Access is satisfactory. However, our study presents high‐resolution insights which could serve as points of leverage for policymakers to mitigate inequalities by designating a new centre and to evaluate potential benefits of centralisation. [ABSTRACT FROM AUTHOR]

Background Given the impact of new antiretroviral drugs on weight and metabolic parameters, their potential contribution to the development of liver steatosis is of concern. We investigated the determinants of liver steatosis in patients on antiretroviral therapy (ART) in the Swiss HIV Cohort Study (SHCS). Methods Between 2019 and 2021, we measured liver stiffness and controlled attenuation parameter (CAP) using transient elastography in consecutive SHCS participants at Bern University Hospital. Individuals with viral hepatitis coinfection and pregnant women were excluded. We used multivariable logistic regression to explore factors associated with steatosis. Results Of 416 participants, 113 (27.2%) were female, median age was 51 years (interquartile range [IQR], 43–59), 305 (73.3%) were of European origin, and 212 (51.0%) were overweight/obese (body mass index [BMI] ≥25 kg/m2). Liver steatosis (CAP ≥248 dB/m) was present in 212 (51.0%) participants, 11 (5.2%) of whom had significant fibrosis or cirrhosis. One hundred seventy-nine (43.0%) met the criteria for metabolic-associated fatty liver disease (MAFLD). Among 64 individuals with a BMI <25 kg/m2 and liver steatosis, 31 (48.4%) had MAFLD. In multivariable analyses, BMI ≥25 kg/m2 (adjusted odds ratio, 5.76; 95% confidence interval, 3.57–9.29), age ≥50 years (1.88, 1.14–3.09), European origin (3.16, 1.69–5.89), and current use of tenofovir alafenamide (1.70, 1.08–2.69) were associated with liver steatosis. Exposure to integrase inhibitors was not associated with liver steatosis (0.83, 0.51–1.37). Conclusions Our findings suggest a high prevalence of liver steatosis among people with HIV (PWH) on ART in Switzerland. In addition to established risk factors, the use of tenofovir alafenamide was associated with hepatic steatosis. [ABSTRACT FROM AUTHOR]

Machine learning is increasingly introduced into medical fields, yet there is limited evidence for its benefit over more commonly used statistical methods in epidemiological studies. We introduce an unsupervised machine learning framework for longitudinal features and evaluate it using sexual behaviour data from the last 20 years from over 3'700 participants in the Swiss HIV Cohort Study (SHCS). We use hierarchical clustering to find subgroups of men who have sex with men in the SHCS with similar sexual behaviour up to May 2017, and apply regression to test whether these clusters enhance predictions of sexual behaviour or sexually transmitted diseases (STIs) after May 2017 beyond what can be predicted with conventional parameters. We find that behavioural clusters enhance model performance according to likelihood ratio test, Akaike information criterion and area under the receiver operator characteristic curve for all outcomes studied, and according to Bayesian information criterion for five out of ten outcomes, with particularly good performance for predicting future sexual behaviour and recurrent STIs. We thus assess a methodology that can be used as an alternative means for creating exposure categories from longitudinal data in epidemiological models, and can contribute to the understanding of time-varying risk factors. Author summary: Machine learning tools are becoming increasingly important in medical research. Yet it is not entirely clear whether these tools perform better than conventional ones when it comes to research on a population level. Here we designed and tested a machine learning method which we use to predict sexually transmitted diseases among HIV-positive men who have sex with men in Switzerland. We used a machine learning algorithm to find groups of men with similar sexual behaviour in the last twenty years, and found that considering these groups in addition to conventional risk factors yielded more accurate predictions of who would be diagnosed with an STI. With this we hope to shed some light on how and to what extent machine learning can help predict and prevent infectious diseases. [ABSTRACT FROM AUTHOR]

Background: Studying human immunodeficiency virus type 1 (HIV-1) superinfection is important to understand virus transmission, disease progression, and vaccine design. But detection remains challenging, with low sampling frequencies and insufficient longitudinal samples.Methods: Using the Swiss HIV Cohort Study (SHCS), we developed a molecular epidemiology screening for superinfections. A phylogeny built from 22 243 HIV-1 partial polymerase sequences was used to identify potential superinfections among 4575 SHCS participants with longitudinal sequences. A subset of potential superinfections was tested by near-full-length viral genome sequencing (NFVGS) of biobanked plasma samples.Results: Based on phylogenetic and distance criteria, 325 potential HIV-1 superinfections were identified and categorized by their likelihood of being detected as superinfections due to sample misidentification. NFVGS was performed for 128 potential superinfections; of these, 52 were confirmed by NFVGS, 15 were not confirmed, and for 61 sampling did not allow confirming or rejecting superinfection because the sequenced samples did not include the relevant time points causing the superinfection signal in the original screen. Thus, NFVGS could support 52 of 67 adequately sampled potential superinfections.Conclusions: This cohort-based molecular approach identified, to our knowledge, the largest population of confirmed superinfections, showing that, while rare with a prevalence of 1%-7%, superinfections are not negligible events. [ABSTRACT FROM AUTHOR]

SHCS#879 is an ongoing Switzerland-wide multicenter observational study conducted within the Swiss HIV Cohort Study (SHCS) for the prospective follow-up of people living with HIV (PLWH) receiving long-acting injectable cabotegravir-rilpivirine (LAI-CAB/RPV). All adults under LAI-CAB/RPV and part of SHCS are enrolled in the project. The study addresses an integrated strategy of treatment monitoring outside the stringent frame of controlled clinical trials, based on relevant patient characteristics, clinical factors, potential drug-drug interactions, and measurement of circulating blood concentrations. So far, 91 blood samples from 46 PLWH have been collected. Most individuals are less than 50 years old, with relatively few comorbidities and comedications. The observed concentrations are globally in accordance with the available values reported in the randomized clinical trials. Yet, low RPV concentrations not exceeding twice the reported protein-adjusted 90% inhibitory concentration have been observed. Data available at present confirm a considerable between-patient variability overall. Based on the growing amount of PK data accumulated during this ongoing study, population pharmacokinetic analysis will characterize individual concentration-time profiles of LAI-CAB/RPV along with their variability in a real-life setting and their association with treatment response and tolerability, thus bringing key data for therapeutic monitoring and precision dosage adjustment of this novel long-acting therapy. [ABSTRACT FROM AUTHOR]

Over the last decade, syphilis diagnoses among men-who-have-sex-with-men (MSM) have strongly increased in Europe. Understanding the drivers of the ongoing epidemic may aid to curb transmissions. In order to identify the drivers of syphilis transmission in MSM in Switzerland between 2006 and 2017 as well as the effect of potential interventions, we set up an epidemiological model stratified by syphilis stage, HIV-diagnosis, and behavioral factors to account for syphilis infectiousness and risk for transmission. In the main model, we used 'reported non-steady partners' (nsP) as the main proxy for sexual risk. We parameterized the model using data from the Swiss HIV Cohort Study, Swiss Voluntary Counselling and Testing center, cross-sectional surveys among the Swiss MSM population, and published syphilis notifications from the Federal Office of Public Health. The main model reproduced the increase in syphilis diagnoses from 168 cases in 2006 to 418 cases in 2017. It estimated that between 2006 and 2017, MSM with HIV diagnosis had 45.9 times the median syphilis incidence of MSM without HIV diagnosis. Defining risk as condomless anal intercourse with nsP decreased model accuracy (sum of squared weighted residuals, 378.8 vs. 148.3). Counterfactual scenarios suggested that increasing screening of MSM without HIV diagnosis and with nsP from once every two years to twice per year may reduce syphilis incidence (at most 12.8% reduction by 2017). Whereas, increasing screening among MSM with HIV diagnosis and with nsP from once per year to twice per year may substantially reduce syphilis incidence over time (at least 63.5% reduction by 2017). The model suggests that reporting nsP regardless of condom use is suitable for risk stratification when modelling syphilis transmission. More frequent screening of MSM with HIV diagnosis, particularly those with nsP may aid to curb syphilis transmission. Author summary: Syphilis, one of the most common sexually transmitted infections, remains a major public health problem. Over the last decade, a rising number of diagnoses especially in men-who-have-sex-with-men (MSM) was observed in Western Europe and Northern America. In Switzerland, the number of syphilis diagnoses in MSM tripled between 2006 and 2017. In this study, we used a mathematical model to assess the drivers of this increase among MSM in Switzerland. Our model could reproduce the increase in syphilis diagnoses in both MSM with and without HIV diagnosis between 2006 and 2017. Based on this model we found that MSM with HIV diagnosis have an over 45 times higher syphilis incidence than MSM without HIV diagnosis. Furthermore, we found that reported sex with non-steady partners is a useful proxy of behavioral risk. Considering counterfactual scenarios, we showed that increasing the screening frequency for syphilis among MSM with HIV diagnosis and with non-steady partners from once a year to twice per year can reduce syphilis incidence by 63.5% to 99.2%. [ABSTRACT FROM AUTHOR]

Background: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform.Methods: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19").Discussion: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland.Trial Registration: ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021. [ABSTRACT FROM AUTHOR]

Purpose: According to the principle of equivalence of care, health care in prison has to be of the same standard and quality as in the general population. This study aims to determine the geographic accessibility of dialysis services for older prisoners and the older general population in Switzerland and whether accessibility and availability of dialysis care are equivalent.Design/methodology/approach: Spatial accessibility analysis incorporated four different data types: population data, administrative data, street network data and addresses of prisons and hemodialysis services.Findings: Analysis revealed that the average travel time to the nearest dialysis service was better for prisoners (11.5 min) than for the general population (14.8 min). However, dialysis service for prisoners is hampered by the necessary lead-time in correctional settings, which, ultimately, leads to longer overall access times (36.5 min). Accordingly, the equivalence of dialysis care for older Swiss prisoners is not entirely respected for availability and accessibility.Originality/value: The strength of the study lies in the combination of ethical principles and the highly tangible results of a spatial accessibility analysis. The ethics-driven empirical analysis provides arguments for policy-makers to review the current practices. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether data-driven machine learning models, which are trained on large epidemiological cohorts, may improve prediction of comorbidities in people living with human immunodeficiency virus (HIV).Methods: In this proof-of-concept study, we included people living with HIV in the prospective Swiss HIV Cohort Study with a first estimated glomerular filtration rate (eGFR) >60 mL/minute/1.73 m2 after 1 January 2002. Our primary outcome was chronic kidney disease (CKD)-defined as confirmed decrease in eGFR ≤60 mL/minute/1.73 m2 over 3 months apart. We split the cohort data into a training set (80%), validation set (10%), and test set (10%), stratified for CKD status and follow-up length.Results: Of 12 761 eligible individuals (median baseline eGFR, 103 mL/minute/1.73 m2), 1192 (9%) developed a CKD after a median of 8 years. We used 64 static and 502 time-changing variables: Across prediction horizons and algorithms and in contrast to expert-based standard models, most machine learning models achieved state-of-the-art predictive performances with areas under the receiver operating characteristic curve and precision recall curve ranging from 0.926 to 0.996 and from 0.631 to 0.956, respectively.Conclusions: In people living with HIV, we observed state-of-the-art performances in forecasting individual CKD onsets with different machine learning algorithms. [ABSTRACT FROM AUTHOR]

Objectives: We previously demonstrated an association between tenofovir disoproxil fumarate (TDF) and chronic liver enzyme elevation in the D:A:D study. The objective of the study was to assess changes in alanine aminotransferase (ALT) levels after switching from TDF to tenofovir alafenamide (TAF). Methods: We included Swiss HIV Cohort Study participants who switched from TDF to TAF with two or more ALT values in the 24 months before and two or more values in the 24 months after replacing TDF with TAF. Individuals with replicating viral hepatitis were excluded. Uni‐ and multivariable linear mixed models were used to explore changes in ALT values associated with switching from TDF to TAF, and to assess potential modifying effects. Results: A total of 1712 participants were included, contributing 6169 ALT values before and 5482 after switching. Median (interquartile range, IQR) age was 50 (42–57) years, and 75% were male. Median (IQR) ALT was 28 (22–38) U/L before and 24 (19–32) U/L after replacing TDF with TAF. ALT values decreased by 3.7 U/L (95% confidence interval: 3.2–4.2) after the switch. The median drop was larger in patients with chronic ALT elevation (defined as two or more elevated values for ≥ 6 months) compared with patients with normal ALT values (17.8 vs. 3.3 U/L, P < 0.001). We did not identify any major effect modifications of the ALT change with any of the potential variables studied. Conclusions: Replacing TDF with TAF in HIV‐monoinfected people led to a significant decrease in ALT values. Findings were not significantly affected by known risk factors for hepatotoxicity. [ABSTRACT FROM AUTHOR]

Background Identifying local outbreaks and their drivers is a key step toward curbing human immunodeficiency virus (HIV) transmission and potentially achieving HIV elimination. Such outbreaks can be identified as transmission clusters extracted from phylogenetic trees constructed of densely sampled viral sequences. In this study, we combined phylogenetic transmission clusters with extensive data on virological suppression and behavioral risk of cluster members to quantify the drivers of ongoing transmission over 10 years. Methods Using the comprehensive Swiss HIV Cohort Study and its drug-resistance database, we reconstructed phylogenetic trees for each year between 2007 and 2017. We identified HIV transmission clusters dominated by men who have sex with men (MSM) and determined their annual growth. We used Poisson regression to assess if cluster growth was associated with a per-cluster infectivity and behavioral risk score. Results Both infectivity and behavioral risk scores were significantly higher in growing MSM transmission clusters compared to nongrowing clusters (P  ≤ .01). The fraction of transmission clusters without infectious members acquiring new infections increased significantly over the study period. The infectivity score was significantly associated with per-capita incidence of MSM transmission clusters in 8 years, while the behavioral risk score was significantly associated with per-capita incidence of MSM transmission clusters in 3 years. Conclusions We present a phylogenetic method to identify hotspots of ongoing transmission among MSM. Our results demonstrate the effectiveness of treatment as prevention at the population level. However, the significantly increasing number of new infections among transmission clusters without infectious members highlights a relative shift from diagnosed to undiagnosed individuals as drivers of HIV transmission in Swiss MSM. [ABSTRACT FROM AUTHOR]

Background: Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain.Objective: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF.Design: Cohort study.Setting: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland.Participants: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer.Measurements: Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions Z tests.Results: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months.Limitation: Short follow-up, small subgroup analyses, and potential residual confounding.Conclusion: Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels.Primary Funding Source: Swiss National Science Foundation. [ABSTRACT FROM AUTHOR]

Background: Replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) improves renal tubular markers in HIV-infected individuals but the impact on estimated glomerular filtration rate (eGFR) remains unclear.Methods: In all participants from the Swiss HIV Cohort Study who switched from TDF to TAF-containing antiretroviral regimen or continued TDF, we estimated changes in eGFR and urine protein-to-creatinine ratio (UPCR) after 18 months using mixed-effect models.Results: Of 3520 participants (26.6% women, median age 50 years), 2404 (68.5%) switched to TAF. Overall, 1664 (47.3%) had an eGFR <90 mL/min and 1087 (30.9%) an UPCR ≥15 mg/mmol. In patients with baseline eGFR ≥90 mL/min, eGFR decreased with the use of TDF and TAF (-1.7 mL/min). Switching to TAF was associated with increases in eGFR of 1.5 mL/min (95% confidence interval [CI], .5-2.5) if the baseline eGFR was 60-89 mL/min, and 4.1 mL/min (95% CI, 1.6-6.6) if <60 mL/min. In contrast, eGFR decreased by 5.8 mL/min (95% CI, 2.3-9.3) with continued use of TDF in individuals with baseline eGFR <60 mL/min. UPCR decreased after replacing TDF by TAF, independent of baseline eGFR.Conclusions: Switching from TDF to TAF improves eGFR and proteinuria in patients with renal dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: Chemsex refers to the use of sex‐enhancing drugs among men who have sex with men (MSM) in combination with specific sexual and social behaviours. Longitudinal data on this development and the associated health risks are scarce. Methods: Data on all recreational drugs reported in the Swiss HIV Cohort Study (SHCS) from 2007 to 2017 were collected. Drug use was analysed longitudinally for all drug classes. In addition, potential associations between patient characteristics and the consumption of methamphetamine, γ‐hydroxybutric acid/γ‐butyrolactone (GHB/GBL), 3,4‐methylenedioxymethamphetamine (MDMA/XTC), cocaine and amphetamine were analysed. Results: We analysed 166 167 follow‐up entries for 12 527 SHCS participants, including 7101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, we observed a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P < 0.001) and GHB/GBL (from 1.0 to 3.4%; P < 0.001). The use of each of the potentially sex‐enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with nonsteady partners, and higher prevalences of depression, syphilis and hepatitis C. Conclusions: The significant increase in the use of chemsex drugs among MSM in the SHCS and the strong association with coinfections and depression highlights the need for harm reduction programmes tailored to MSM. According to our results, improving knowledge about recreational drugs is important for all health care professionals working with people living with HIV. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to investigate strategies to prevent and treat cetuximab-induced skin reactions and their perceived effectiveness in patients with metastatic colorectal cancer (mCRC) and recurrent/metastatic squamous cell cancer of the head and neck (SCCHN).Methods: This open-label, prospective observational study was conducted in Switzerland.Results: A total of 125 patients were included (n = 91 mCRC, n = 34 SCCHN; mean age 63.3 years; 73.6% males). The frequency of acneiform rash grade ≥ 2 increased from 12.6% at week 2 to 21.7% at week 16. The proportion of patients who reported no skin reaction decreased from 75.6% at week 2 to 43.3% at week 16. The most frequently used skin products at any time of observation were moisturizing (77.6%), lipid-regenerating (56.8%) or urea-containing products (52%), systemic antibiotics (49.6%), and vitamin K1 cream (43.2%). There was no clear effectiveness pattern for all product classes: in given patients, either the product showed no effect at all or a moderate/strong effect, consistently over time.Conclusions: A great variety of low-cost general skin care products were commonly used. According to physician's preference, systemic antibiotics and vitamin K1 cream are an appropriate approach to prevent or treat cetuximab-related skin toxicity. [ABSTRACT FROM AUTHOR]

Background The proportion of undiagnosed hepatitis C virus (HCV) infections in high-risk populations, such as human immunodeficiency virus (HIV)–infected men who have sex with men (MSM) is unclear. Identification of potential HCV transmitters is important to reach World Health Organization HCV elimination targets. Methods Between October 2015 and May 2016, we performed a systematic HCV RNA–based screening among HIV-infected MSM participating in the Swiss HIV Cohort Study (SHCS). HCV antibodies were measured from all HCV RNA–positive samples. Results Of 4257 MSM recorded in the SHCS database, we screened 3722 (87%) by HCV polymerase chain reaction, and 177 (4.8%) harbored a replicating HCV infection. We identified 24 individuals (14%) with incident HCV infection; one-third of them had a negative HCV antibody result at the time of HCV RNA positivity. In a multivariable model, elevated liver enzyme values (odds ratio, 14.52; 95% confidence interval, 9.92–21.26), unprotected sex with occasional partners (2.01; 1.36–2.98), intravenous drug use (7.13; 4.36–11.64), noninjectable drug use (1.94; 1.3–2.88), and previous syphilis diagnosis (2.56; 1.74–3.76) were associated with HCV RNA positivity. Conclusions A systematic HCV RNA–based screening among HIV-infected MSM revealed a high number of potential transmitters. A substantial subpopulation of MSM had incident infection, one-third of whom had a negative HCV antibody test result at the time of the HCV RNA positivity. These data reveal that one-time RNA testing of a high-risk population for HCV RNA might identify more infected persons than routine testing for HCV antibodies and liver enzymes. Clinical Trials Registration NCT02785666 [ABSTRACT FROM AUTHOR]

Objectives: Despite the huge success of antiretroviral therapy (ART), there is an ongoing HIV epidemic among men who have sex with men (MSM) in resource‐rich countries. Understanding the driving factors underlying this process is important for curbing the epidemic. Methods: We simulated the HIV epidemic in MSM in Switzerland by stratifying a mathematical model by CD4 count, the care cascade and condom use. The model was parametrised with clinical, epidemiological and behavioural data from the Swiss HIV Cohort Study and surveys in the HIV‐negative population. Results: According to our model, 3.4% of the cases that would otherwise have occurred in 2008–2015 were prevented by early initiation of ART. Only 0.6% of the cases were attributable to a change in condom use in the HIV‐positive population, as less usage is mainly seen in virally suppressed MSM. Most new infections were attributable to transmission from recently infected undiagnosed individuals. It was estimated that doubling the diagnosis rate would have resulted in 11.8% fewer cases in 2001–2015. Moreover, it was estimated that introducing pre‐exposure prophylaxis (PrEP) for 50% of those MSM not using condoms with occasional partners would have resulted in 22.6% fewer cases in 2012–2015. Conclusions: By combining observational data on the relevant epidemiological and clinical processes with a mathematical model, we showed that the 'test and treat' approach is most effective in reducing the number of new cases. Only a moderate population‐level effect was estimated for early initiation of ART and a weak effect for the change in condom use of diagnosed MSM. Protecting HIV‐negative individuals who are not using condoms with PrEP was shown to have a major impact. [ABSTRACT FROM AUTHOR]

To investigate the association between a wide set of baseline characteristics (age, sex, rehabilitation discipline), functional scores [Functional Independence Measure (FIM), cumulative Illness Rating Scale (CIRS)], diseases, and administered drugs and incident delirium in rehabilitation inpatients and, furthermore, to assess clinical implications of developing delirium during rehabilitation. Matched case-control study based on electronic health record data. We studied rehabilitation stays of inpatients admitted between January 1, 2015, and December 31, 2018, to ZURZACH Care, Rehaklinik Bad Zurzach, an inpatient rehabilitation clinic in Switzerland. We conducted unconditional logistic regression analyses to estimate adjusted odds ratios (AORs) with 95% CIs of exposures that were recorded in ≥5 cases and controls. Among a total of 10,503 rehabilitation stays, we identified 125 validated cases. Older age, undergoing neurologic rehabilitation, a low FIM, and a high CIRS were associated with an increased risk of incident delirium. Being diagnosed with a bacterial infection (AOR 2.62, 95% CI 1.06-6.49), a disorder of fluid, electrolyte, or acid-base balance (AOR 2.76, 95% CI 1.19-6.38), Parkinson's disease (AOR 5.68, 95% CI 2.54-12.68), and administration of antipsychotic drugs (AOR 8.06, 95% CI 4.26-15.22), antiparkinson drugs (AOR 2.86, 95% CI 1.42-5.77), drugs for constipation (AOR 2.11, 95% CI 1.25-3.58), heparins (AOR 2.04, 95% CI 1.29-3.24), or antidepressant drugs (AOR 1.88, 95% CI 1.14-3.10) during rehabilitation, or an increased anticholinergic burden (ACB ≥ 3) (AOR 2.59, 95% CI 1.41-4.73) were also associated with an increased risk of incident delirium. We identified a set of factors associated with an increased risk of incident delirium during inpatient rehabilitation. Our findings contribute to detect patients at risk of delirium during inpatient rehabilitation. [ABSTRACT FROM AUTHOR]

Objectives Direct-acting antiviral agents ( DAAs) have become the standard of care for the treatment of chronic hepatitis C virus ( HCV) infection. We aimed to assess treatment uptake and efficacy in routine clinical settings among HIV/HCV coinfected patients after the introduction of the first generation DAAs. Methods Data on all Swiss HIV Cohort Study ( SHCS) participants starting HCV protease inhibitor ( PI) treatment between September 2011 and August 2013 were collected prospectively. The uptake and efficacy of HCV therapy were compared with those in the time period before the availability of PIs. Results Upon approval of PI treatment in Switzerland in September 2011, 516 SHCS participants had chronic HCV genotype 1 infection. Of these, 57 (11%) started HCV treatment during the following 2 years with either telaprevir, faldaprevir or boceprevir. Twenty-seven (47%) patients were treatment-naïve, nine (16%) were patients with relapse and 21 (37%) were partial or null responders. Twenty-nine (57%) had advanced fibrosis and 15 (29%) had cirrhosis. End-of-treatment virological response was 84% in treatment-naïve patients, 88% in patients with relapse and 62% in previous nonresponders. Sustained virological response was 78%, 86% and 40% in treatment-naïve patients, patients with relapse and nonresponders, respectively. Treatment uptake was similar before (3.8 per 100 patient-years) and after (6.1 per 100 patient-years) the introduction of PIs, while treatment efficacy increased considerably after the introduction of PIs. Conclusions The introduction of PI-based HCV treatment in HIV/HCV-coinfected patients improved virological response rates, while treatment uptake remained low. Therefore, the introduction of PIs into the clinical routine was beneficial at the individual level, but had only a modest effect on the burden of HCV infection at the population level. [ABSTRACT FROM AUTHOR]

Study design:Secondary data analysis of a questionnaire-based, cross-sectional survey in persons with spinal cord injury (SCI) in Switzerland.Objective:To describe the frequency of participation in sport (PiS) and to identify correlates for PiS in persons with SCI in Switzerland.Setting:Community sampleMethods:Frequency of PiS was assessed retrospectively for the time before the onset of SCI and the time of the survey using a single-item question. A comprehensive set of independent variables was selected from the original questionnaire. Descriptive statistics, bivariate analyses and ordinal regressions were carried out.Results:Data from 505 participants were analyzed. Twenty independent variables were selected for analyses. PiS decreased significantly from the time before the onset of SCI to the time of the survey (P<0.001). Sport levels were significantly lower in women than men for the time of the survey (P<0.001), whereas no difference was observed before onset of SCI (P=0.446). Persons with tetraplegia participated significantly less often in sport than persons with paraplegia (P<0.001). Lesion level, active membership in a club, frequency of PiS before the onset of SCI and the subjective evaluation of the importance of sport correlate with PiS. When controlling for gender differences, only the subjective importance of sport for persons with SCI determines PiS, particularly among women.Conclusions:Persons with tetraplegia and women need special attention when planning interventions to improve PiS. Furthermore, the subjective importance of sport is important for PiS, particularly among women, whereas most other factors were only weakly associated with PiS. [ABSTRACT FROM AUTHOR]

Switzerland has a complex human immunodeficiency virus (HIV) epidemic involving several populations. We examined transmission of HIV type 1 (HIV-1) in a national cohort study. Latent class analysis was used to identify socioeconomic and behavioral groups among 6,027 patients enrolled in the Swiss HIV Cohort Study between 2000 and 2011. Phylogenetic analysis of sequence data, available for 4,013 patients, was used to identify transmission clusters. Concordance between sociobehavioral groups and transmission clusters was assessed in correlation and multiple correspondence analyses. A total of 2,696 patients were infected with subtype B, 203 with subtype C, 196 with subtype A, and 733 with recombinant subtypes (mainly CRF02_AG and CRF01_AE). Latent class analysis identified 8 patient groups. Most transmission clusters of subtype B were shared between groups of gay men (groups 1–3) or between the heterosexual groups “heterosexual people of lower socioeconomic position” (group 4) and “injection drug users” (group 8). Clusters linking homosexual and heterosexual groups were associated with “older heterosexual and gay people on welfare” (group 5). “Migrant women in heterosexual partnerships” (group 6) and “heterosexual migrants on welfare” (group 7) shared non-B clusters with groups 4 and 5. Combining approaches from social and molecular epidemiology can provide insights into HIV-1 transmission and inform the design of prevention strategies. [ABSTRACT FROM PUBLISHER]

Background Three-dimensional transesophageal echocardiography (3D TEE) has been demonstrated to provide more accurate information than two-dimensional transesophageal echocardiography (2D TEE) in the localization of mitral valve prolapse ( MVP). However, most studies have been single-rater studies. Few results were tested for inter-observer variability with a single second rater. This multicenter study aimed to determine reliability of 2D and 3D TEE mitral valve evaluations by calculating inter-observer agreement between various echocardiographers. Methods Fifteen observers from 4 institutions in Germany and Switzerland interpreted 2D and 3D TEE images from 6 patients selected to represent a large spectrum of MVP diversity. Surgical findings served as reference. Individual assessments of MVP and ruptured chordae tendineae (ChR) pathology were compared by calculating Randolph's free-marginal multirater kappa coefficient. Results Accuracy of MVP evaluation with 3D TEE was 83.9%, CI [81.0%; 86.8%] and 78.7% CI [76.6% 80.8%] with 2D TEE. Flail leaflets with chordal ruptures were described correctly in 91.1%, CI [85.8, 96.4] with 3D compared to 71.1%, CI [65.0, 77.2] with 2D TEE. The multirater kappa coefficient of inter-observer agreement among all 15 observers was κ = 0.65/0.58 for 3D/2D evaluation of MVP and κ = 0.70/0.54 for detection of ChR. Conclusion Three-dimensional assessment of MVP was superior to 2D TEE, although the accuracy of both 3D TEE and 2D TEE was found to be lower than previously published. 3D MVP assessment is less operator dependent than 2D TEE evaluation. Although validity has been demonstrated before, we provide evidence that 3D TEE is reproducible among 15 observers and is a reliable method for MVP evaluation. [ABSTRACT FROM AUTHOR]

Objectives Antiretroviral therapy ( ART) suppresses HIV viraemia, thereby reducing the antigenic drive for T cells to proliferate. Accordingly, selected HIV-specific T-cell responses have been described to contract within weeks of ART initiation. Here, we sought to investigate whether these findings apply to the entire repertoire of HIV-specific T cells. Methods Using interferon ( IFN)-γ enzyme linked immuno spot ( ELISpot), we performed retrospective 2-year proteome-wide monitoring of HIV-specific T cells in 17 individuals with undetectable viral loads during ART. The sample pool for each study subject consisted of one pre- ART time-point and at least two time-points after initiation of therapy. Results Peripheral pools of HIV-specific T cells decreased nonsignificantly within the first 2 years under ART in our cohort of patients, in terms of both breadth and magnitude. However, in most cases, the seeming decrease masked ongoing expansion of individual HIV-specific T-cell responses. We detected synchronous contraction and expansion of T-cell responses - with different peptide specificities - in 12 out of 17 study participants during follow-up. Importantly, the observed expansions and contractions of individual HIV-specific T-cell responses reached similar ranges, supporting the biological relevance of our findings. Conclusions We conclude that successful ART enables both contraction and expansion of HIV-specific T-cell responses. Our results should prompt a renewed interest in HIV-specific T-cell dynamics under ART, in particular to elucidate the mechanisms that uncouple, to some extent, particular HIV-specific T-cell responses from variations in circulating antigen load and functionally characterize expanding/contracting T-cell populations beyond IFN-γ secretion. Assuming that expanding HIV-specific T-cell responses under ART are protective and functional, harnessing those mechanisms may provide novel opportunities for assisting viral control in chronically infected individuals. [ABSTRACT FROM AUTHOR]

Objectives: Vocational rehabilitation (VR) plays a key role in bringing persons with acquired disabilities back to work, while encouraging employment participation. The purpose of this case study is to illustrate the systematic application of International Classification of Functioning, Disability, and Health (ICF)-based documentation tools by using ICF Core Sets in VR shown with a case example of a client with traumatic spinal cord injury (SCI). Participant: The client was a 26-year-old male with paraplegia (7th thoracic level), working in the past as a mover. Methods: This case study describes the integration of the ICF Core Sets for VR into an interdisciplinary rehabilitation program by using ICF-based documentation tools. Results: Improvements in the client's impairments, activity limitations, and participation restrictions were observed following rehabilitation. Goals in different areas of functioning were achieved. Conclusion: The use of the ICF Core Sets in VR allows a comprehensive assessment of the client's level of functioning and intervention planning. Specifically, the Brief ICF Core Set in VR can provide domains for intervention relevant to each member of an interdisciplinary team and hence, can facilitate the VR management process in a SCI center in Switzerland. [ABSTRACT FROM AUTHOR]

An in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted interventions. [ABSTRACT FROM AUTHOR]

Background. Estimates of the decrease in CD4+ cell counts in untreated patients with human immunodeficiency virus (HIV) infection are important for patient care and public health. We analyzed CD4+ cell count decreases in the Cape Town AIDS Cohort and the Swiss HIV Cohort Study. Methods. We used mixed-effects models and joint models that allowed for the correlation between CD4+ cell count decreases and survival and stratified analyses by the initial cell count (50-199, 200-349, 350-499, and 500- 750 cells/μL). Results are presented as the mean decrease in CD4+ cell count with 95% confidence intervals (CIs) during the first year after the initial CD4+ cell count. Results. A total of 784 South African (629 nonwhite) and 2030 Swiss (218 nonwhite) patients with HIV infection contributed 13,388 CD4+ cell counts. Decreases in CD4+ cell count were steeper in white patients, patients with higher initial CD4+ cell counts, and older patients. Decreases ranged from a mean of 38 cells/μL (95% CI, 24-54 cells/μL) in nonwhite patients from the Swiss HIV Cohort Study 15-39 years of age with an initial CD4+ cell count of 200-349 cells/μL to a mean of 210 cells/μL (95% CI, 143-268 cells/μL) in white patients in the Cape Town AIDS Cohort ⩾40 years of age with an initial CD4+ cell count of 500-750 cells/μL. Conclusions. Among both patients from Switzerland and patients from South Africa, CD4+ cell count decreases were greater in white patients with HIV infection than they were in nonwhite patients with HIV infection. [ABSTRACT FROM AUTHOR]

Features the 1st European Seminar on Environmental Engineering Education slated in August 1999 in Zurich, Switzerland. Educational needs of environmental engineers; Compatibility and comparability of the systems of environmental engineering education; Accreditation.

Introduction: The clinical spectrum of injuries in crevasse accidents can range from benign to life-threatening, even including death. To date, little is known about incidence and causes.Methods: We retrospectively analyzed mountain rescue missions that included crevasse accidents and took place in Switzerland from 2010 to 2020. Demographic and epidemiological data were collected. Injury severity was graded according to the National Advisory Committee for Aeronautics (NACA) score. Winter season was defined as December to May, and summer season as June to November.Results: A total of 321 victims of crevasse falls were included in the study. The median age of victims was 41.2 years (interqauartile range [IQR] 31.3 to 51.6), with 82% (n=260) being male and 59% (n=186) foreigners. The typical altitude range at which rescue missions were performed was between 3000 and 3499m (44% of all cases). The median depth of the fall was 15 meters (IQR 8 to 20) during the winter season compared to 8 meters (IQR 5 to 10) during the summer, p<0.001. Overall mortality was 6.5%. The NACA score was ≥4 for 9.4% (n=30) of the victims. 55% (n=177) had a NACA score of 0 or 1. There was a significant positive correlation between the depth of fall and the injury severity (Pearson`s correlation r=0.35, 95%- confidence interval: 0.18 to 0.51), p<0.001.Conclusion: More than half of victims fallen into a crevasse are uninjured or sustain mild injury. Life-threathening injuries were found in about 10% of victims and the crevasse fall was fatal in 6.5% of cases. Injury severity positively correlates with the depth of fall, which is higher during winter season. [ABSTRACT FROM AUTHOR]

Background: Tenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or impaired renal function.Methods: We included all participants of the Swiss HIV Cohort Study on TDF-containing antiretroviral therapy with follow-up visits after January 2016. We determined the proportion of switches from TDF to TAF overall, and among patients with risk factors for TDF toxicity, including osteoporosis, impaired renal function or marked proteinuria. We used multivariable logistic regression to explore predictors of switching from TDF to TAF.Results: We included 5'012 patients, of whom 652 (13.0%) had risk factors for TDF toxicity. A switch from TDF to TAF was undertaken in 2'796 (55.8%) individuals overall, and in 465 (71.3%) with risk factors. Predictors of switching to TAF were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.07-1.50), age > 50 years (1.43, 1.23-1.66) and the presence of risk factors for TDF toxicity (2.21, 1.77-2.75). In contrast, patients with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-pill regimen (0.11, 0.09-0.13), those treated in non-tertiary care centers (0.56, 0.46-0.70), as well as those with CD4 cell counts below 500/μL (0.77, 0.66-0.90) and with chronic hepatitis C infection (0.66, 0.54-0.80) were most likely to stay on TDF.Conclusions: Over 50% of patients on TDF-containing therapy, including the majority of patients at risk for TDF toxicity, were switched to TAF within two years of its introduction in Switzerland. Individuals on NNRTI-based single-pill regimens were most likely to remain on TDF. [ABSTRACT FROM AUTHOR]

Swiss national recommendations advise, since end of 2018, supporting women with HIV who wish to breastfeed. Our objective is to describe the motivational factors and the outcome of these women and of their infants. mothers included in MoCHiV with a delivery between January 2019 and February 2021 who fulfilled the criteria of the "optimal scenario" (adherence to cART, regular clinical care, and suppressed HIV plasma viral load (pVL) of <50 RNA copies/ml) and who decided to breastfeed after a shared decision-making process, were approached to participate in this nested study and asked to fill-in a questionnaire exploring the main motivating factors for breastfeeding. Between January 9, 2019 and February 7, 2021, 41 women gave birth, and 25 decided to breastfeed of which 20 accepted to participate in the nested study. The three main motivational factors of these women were bonding, neonatal and maternal health benefits. They breastfed for a median duration of 6.3 months (range 0.7–25.7, IQR 2.5–11.1). None of the breastfed neonates received HIV post-exposure prophylaxis. There was no HIV transmission: 24 infants tested negative for HIV at least 3 months after weaning; one mother was still breastfeeding when we analyzed the data. As a result of a shared decision-making process, a high proportion of mothers expressed a desire to breastfeed. No breastfed infant acquired HIV. The surveillance of breastfeeding mother-infant pairs in high resource settings should be continued to help update guidelines and recommendations. [ABSTRACT FROM AUTHOR]

Supersymmetry with heavy scalars is a model where, at the LHC we have to rely on rate measurements to determine the parameters of the underlying new physics. For this example we show how to combine rate measurements with kinematic endpoints properly, taking into account statistical, systematic and theoretical uncertainties. Provided we observe a sizeable number of events, the LHC should be able to determine many model parameters with small enough error bars to, for example, test unification patterns. [ABSTRACT FROM AUTHOR]

Abstract: Interpretations of Higgs searches critically involve production cross sections and decay probabilities for different analysis channels. Mixing effects can reduce production rates, while invisible decays can reduce decay probabilities. Both effects may transparently be quantified in Higgs systems where a visible Higgs boson is mixed with a hidden sector Higgs boson. Recent experimental exclusion bounds can be re-interpreted in this context as a sign for non-standard Higgs properties. Should a light Higgs boson be discovered, then our analysis will quantify how closely it may coincide with the Standard Model. [Copyright &y& Elsevier]

Abstract: In this Letter we report on a calculation of jet production at next-to-leading order QCD. We include the leptonic decays of the W and take into account all off-shell and finite width effects. This is the first computation which falls into the category of triboson+jet production at next-to-leading order QCD. In total we find sizable corrections with non-trivial phase space dependencies. Therefore, our results are important for phenomenological analyses such as the extraction of anomalous electroweak quartic couplings from inclusive hadron collider data. [Copyright &y& Elsevier]

Abstract: We present a computation of the QCD corrections to production at the Large Hadron Collider. The photon is considered as real, and we include full leptonic decays for the W- and Z-bosons. Based on the structure of the VBFNLO program package, we obtain numerical results via a Monte Carlo program, which allows to implement general cuts and distributions of the final-state particles. The NLO QCD corrections are sizable and strongly exceed the theory error obtained by a scale variation of the leading-order result. Also, the shapes of relevant observables are significantly altered. [ABSTRACT FROM AUTHOR]

Among people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants. We included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability. Of the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm3 (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72–1.91]). Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3–2.6] vs. 0.8/100 PY [95 % CI = 0.7–0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0–1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15–2.61]). Post-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era. [ABSTRACT FROM AUTHOR]

Background KRAS mutation occurs in ∼40% of locally advanced rectal cancers (LARCs). The multitarget tyrosine kinase inhibitor sorafenib has radiosensitising effects and might improve outcomes for standard preoperative chemoradiotherapy in patients with KRAS -mutated LARC. Methods Adult patients with KRAS -mutated T3/4 and/or N1/2M0 LARC were included in this phase I/II study. The phase I dose-escalation study of capecitabine plus sorafenib and radiotherapy was followed by a phase II study assessing efficacy and safety. Primary end-points were to: establish the maximum tolerated dose of the regimen in phase I; determine the pathologic complete response (pCR) rate in phase II defined as Dworak regression grade 3 and 4. Results Fifty-four patients were treated at 18 centres in Switzerland and Hungary; 40 patients were included in the single-arm phase II study. Recommended doses from phase I comprised radiotherapy (45 Gy in 25 fractions over 5 weeks) with capecitabine 825 mg/m 2 twice daily × 33 plus sorafenib 400 mg/d. Median daily dose intensity in phase II was radiotherapy 100%, capecitabine 98.6%, and sorafenib 100%. The pCR rate (Dworak 3/4) was 60% (95% CI, 43.3–75.1%) by central independent pathologic review. Sphincter preservation was achieved in 89.5%, R0 resection in 94.7%, and downstaging in 81.6%. The most common grade 3 toxicities during phase II included diarrhoea (15.0%), skin toxicity outside radiotherapy field (12.5%), pain (7.5%), skin toxicity in radiotherapy field, proctitis, fatigue and cardiac ischaemia (each 5%). Conclusions Combining sorafenib and standard chemoradiotherapy with capecitabine is highly active in patients with KRAS -mutated LARC with acceptable toxicity and deserves further investigation. www.clinicaltrials.gov : NCT00869570 . [ABSTRACT FROM AUTHOR]

Summary Objective To examine the association between hepatitis B virus (HBV) infection and liver fibrosis in HIV-infected patients in Zambia and Switzerland. Methods HIV-infected adults starting antiretroviral therapy in two clinics in Zambia and Switzerland were included. Liver fibrosis was evaluated using the aspartate aminotransferase-to-platelet-ratio index (APRI), with a ratio >1.5 defining significant fibrosis and a ratio >2.0 indicating cirrhosis. The association between hepatitis B surface antigen (HBsAg) positivity, HBV replication, and liver fibrosis was examined using logistic regression. Results In Zambia, 96 (13.0%) of 739 patients were HBsAg-positive compared to 93 (4.5%) of 2058 in Switzerland. HBsAg-positive patients were more likely to have significant liver fibrosis than HBsAg-negative ones: the adjusted odds ratio (aOR) was 3.25 (95% confidence interval (CI) 1.44–7.33) in Zambia and 2.50 (95% CI 1.19–5.25) in Switzerland. Patients with a high HBV viral load (≥20 000 IU/ml) were more likely to have significant liver fibrosis compared to HBsAg-negative patients or patients with an undetectable viral load: aOR 3.85 (95% CI 1.29–11.44) in Zambia and 4.20 (95% CI 1.64–10.76) in Switzerland. In both settings, male sex was a strong risk factor for significant liver fibrosis. Conclusions Despite the differences in HBV natural history between Sub-Saharan Africa and Europe, the degree of liver fibrosis and the association with important risk factors were similar. [ABSTRACT FROM AUTHOR]