Cost-effectiveness and budget effect of pre-exposure prophylaxis for HIV-1 prevention in Germany from 2018 to 2058

Background Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy for men-who-have-sex-with-men (MSM). The high cost of PrEP has until recently been a primary barrier to its use. In 2017, generic PrEP became available, reducing the costs by 90%. Aim Our objective was to assess cost-effectiveness and costs of introducing PrEP in Germany. Methods We calibrated a deterministic mathematical model to the human immunodeficiency virus (HIV) epidemic among MSM in Germany. PrEP was targeted to 30% of high-risk MSM. It was assumed that PrEP reduces the risk of HIV infection by 85%. Costs were calculated from a healthcare payer perspective using a 40-year time horizon starting in 2018. Results PrEP can avert 21,000 infections (interquartile range (IQR): 16,000–27,000) in the short run (after 2 years scale-up and 10 years full implementation). HIV care is predicted to cost EUR 36.2 billion (IQR: 32.4–40.4 billion) over the coming 40 years. PrEP can increase costs by at most EUR 150 million within the first decade after introduction. Ten years after introduction, PrEP can become cost-saving, accumulating to savings of HIV-related costs of EUR 5.1 billion (IQR: 3.5–6.9 billion) after 40 years. In a sensitivity analysis, PrEP remained cost-saving even at a 70% price reduction of antiretroviral drug treatment and a lower effectiveness of PrEP. Conclusion Introduction of PrEP in Germany is predicted to result in substantial health benefits because of reductions in HIV infections. Short-term financial investments in providing PrEP will result in substantial cost-savings in the long term

Antivirale Medikamente.Potente Wirkstoffe, Hoffnungsträger bei COVID‑19 und therapeutische Grenzen.

Antivirale Medikamente hemmen die Virusvermehrung durch Interaktion mit spezifischen Angriffspunkten im viralen Replikationszyklus. Direkt antiviraleWirkstoffe haben die therapeutischen Möglichkeiten bei chronischen Infektionen mit dem humanen Immundefizienz- (HIV), Hepatitis-B- (HBV) und Hepatitis-C-Virus (HCV) revolutioniert. Fortlaufende pharmakologische Entwicklungen sorgen auch bei Erkrankungen durch Herpesviren für verbesserte therapeutische und prophylaktische Möglichkeiten, was insbesondere immunsupprimierten Patientenzugutekommt. Während Infektionen mit persistierenden Viren wie HIV, HBV oder Herpesviren vom Grundsatz her bislang nicht heilbar sind, können Erreger von akuten Virusinfektionen vollständig eliminiert werden. Akute Infektionen, wie Influenza oder „coronavirus disease 2019“ (COVID-19) weisen durch ihre pathophysiologische Dynamik jedoch schmale therapeutische Zeitfenster für antivirale Therapieansätze auf. Der ideale Therapiezeitpunkt liegt hier unmittelbar nach der Virusexposition, was die Anwendung in der Praxis häufig limitiert. Eine effektive antivirale Prä- oderPostexpositionsprophylaxe hat sich bei Infektionen mit HIV und Influenza A/B etabliert und gewinnt aktuell auch bei Infektionen mit dem „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV-2) an Bedeutung

Nonmelanoma skin cancer in mountain guides: High prevalence and lack of awareness warrant development of evidence-based prevention tools.

AIMS OF THE STUDY: Nonmelanoma skin cancer (NMSC) is the most common cancer in Switzerland and Europe. The main causative factor is exposure to ultraviolet radiation, which puts outdoor workers in general at a higher risk of developing NMSC than indoor workers. However, few studies have clinically examined the risk of developing NMSC to outdoor workers, especially mountain guides. We aimed to investigate the prevalence of NMSC and corresponding precancerous lesions, and the associated risk behaviour of mountain and ski guides in order to develop future prevention programmes.METHODS: We conducted a cross-sectional study including mountain and ski guides from southern Germany, who underwent a full-body skin check-up by a dermatologist. We assessed their NMSC awareness and risk behaviour using a paper-based questionnaire.RESULTS: Of the 62 state-certified mountain and ski guides (55 men, 7 women; mean age 52.9 ± 13.4 years) included in this study, 27 (43.5%) were diagnosed with NMSC or its premalignant stages. In addition, 59.7% of the participants expressed the opinion that their protection from ultraviolet radiation exposure needs to be improved; 83.6% requested further information on NMSC, and 48.5% had never undergone a skin check-up or consulted a dermatologist before.CONCLUSIONS: Mountain and ski guides are at a high risk for developing NMSC. Their unmet medical needs indicate an underestimation of NMSC prevalence, which is usually based on reports by insurance companies, and offer the chance for developing evidence-based awareness and prevention tools that can be promoted to individuals with other outdoor jobs

A proof of concept study for the differentiation of SARS-CoV-2, hCoV-NL63, and IAV-H1N1 in vitro cultures using ion mobility spectrometry.

Rapid, high-throughput diagnostic tests are essential to decelerate the spread of the novel coronavirus disease 2019 (COVID-19) pandemic. While RT-PCR tests performed in centralized laboratories remain the gold standard, rapid point-of-care antigen tests might provide faster results. However, they are associated with markedly reduced sensitivity. Bedside breath gas analysis of volatile organic compounds detected by ion mobility spectrometry (IMS) may enable a quick and sensitive point-of-care testing alternative. In this proof-of-concept study, we investigated whether gas analysis by IMS can discriminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from other respiratory viruses in an experimental set-up. Repeated gas analyses of air samples collected from the headspace of virus-infected in vitro cultures were performed for 5 days. A three-step decision tree using the intensities of four spectrometry peaks correlating to unidentified volatile organic compounds allowed the correct classification of SARS-CoV-2, human coronavirus-NL63, and influenza A virus H1N1 without misassignment when the calculation was performed with data 3 days post infection. The forward selection assignment model allowed the identification of SARS-CoV-2 with high sensitivity and specificity, with only one of 231 measurements (0.43%) being misclassified. Thus, volatile organic compound analysis by IMS allows highly accurate differentiation of SARS-CoV-2 from other respiratory viruses in an experimental set-up, supporting further research and evaluation in clinical studies

Self-sampling versus health care professional-guided swab collection for SARS-CoV-2 testing.

PURPOSE: To evaluate the diagnostic reliability and practicability of self-collected oropharyngeal swab samples for the detection of SARS-CoV-2 infection as self-sampling could enable broader testing availability and reduce both personal protective equipment and potential exposure. METHODS: Hospitalized SARS-CoV-2-infected patients were asked to collect two oropharyngeal swabs (SC-OPS1/2), and an additional oropharyngeal swab was collected by a health care professional (HCP-OPS). SARS-CoV-2 PCR testing for samples from 58 participants was performed, with a 48-h delay in half of the self-collected samples (SC-OPS2). The sensitivity, probability of concordance, and interrater reliability were calculated. Univariate and multivariate analyses were performed to assess predictive factors. Practicability was evaluated through a questionnaire. RESULTS: The test sensitivity for HCP-OPS, SC-OPS1, and SC-OPS2 was 88%, 78%, and 77%, respectively. Combining both SC-OPS results increased the estimated sensitivity to 88%. The concordance probability between HCP-OPS and SC-OPS1 was 77.6% and 82.5% between SC-OPS1 and SC-OPS2, respectively. Of the participants, 69% affirmed performing future self-sampling at home, and 34% preferred self-sampling over HCP-guided testing. Participants with both positive HCP-OPS1 and SC-OPS1 indicating no challenges during self-sampling had more differences in viral load levels between HCP-OPS1 and SC-OPS1 than those who indicated challenges. Increasing disease duration and the presence of anti-SARS-CoV-2-IgG correlated with negative test results in self-collected samples of previously confirmed SARS-CoV-2 positive individuals. CONCLUSION: Oropharyngeal self-sampling is an applicable testing approach for SARS-CoV-2 diagnostics. Self-sampling tends to be more effective in early versus late infection and symptom onset, and the collection of two distinct samples is recommended to maintain high test sensitivity

Reopening the Bavarian state opera safely: Hygiene strategies and incidence of COVID-19 in artistic staff during theater season 2020/2021.

Due to the drastically rising coronavirus disease (COVID-19) incidence since March 2020, social life was shut down across the globe, and most opera houses were closed. As a result, there are limited data on SARS-CoV-2 infections among artists. The Bavarian State Opera has been reopened in September 2020. This study aimed to identify the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among employees in the Bavarian State Opera. In addition, the various hygiene strategies for the work groups within the institution are described. During the study period from September 1, 2020 to July 31, 2021, 10,061 nasopharyngeal swabs were obtained from 1,460 artistic staff members in a rolling system. During the entire study period, 61 individuals tested positive for SARS-CoV-2. None of the patients had a severe disease course. Compared to the seven-day-incidence per 100,000 German inhabitants, the estimated corresponding incidence among employees was lower at 37 weeks and higher or equal at 9 weeks. Among the infected individuals, 58.3% were symptomatic, 23.3% were presymptomatic, and 18.3% were asymptomatic. Forty-five percent of employees reported that they had been infected in their private environment, 41.7% suspected that their colleagues were the main contact, and 13.3% were unsure about the origin of their infection. Twenty-four diseased employees were ballet dancers, eight from the orchestra, seven from the administration, seven from the choir singers, six from the costume department, 10 from technical support, and one guest solo singer. In the 2020/2021 theater season, increased SARS-CoV-2 infections and large disease outbreaks were avoided at the Bavarian State Opera. Hygiene strategies, that existed since the beginning, was specifically designed for various work areas in the opera. Regular, mandatory PCR testing and follow-up of positive cases with the issuance of quarantine were performed. Using this disease management approach, artistic work at and reopening of the Bavarian State Opera was feasible with a well-controlled risk

Telemedicine-guided self-collection approach for PCR-based SARS-CoV-2 testing: Comparative study.

BACKGROUND: Large-scale PCR-based SARS-CoV-2 testing is expensive, resource-intensive, and time-consuming. A self-collection approach is a probable alternative; however, it requires evaluating the feasibility, expenses, and the ability to prevent infections. OBJECTIVE: This study aims to compare an innovative self-collection approach with a regular SARS-CoV-2 testing strategy in a large European industrial manufacturing site. METHODS: The feasibility of a telemedical PCR-based self-collection approach was assessed for 150 employees (intervention group) and compared with a regular SARS-CoV-2 testing approach (n=143, control group). Acceptance, ergonomics, and efficacy were evaluated using a software application. A simulation model was implemented to evaluate the effectiveness. An interactive R shiny app was created to enable customized simulations. RESULTS: The test results were successfully communicated and interpreted without uncertainty by 76% and 77% of the participants in the intervention and control groups, respectively (P=.96). The ratings for the acceptability, ergonomics, and efficacy of the intervention group were noninferior when compared with those of the control group (acceptability: 71.6% versus 37.6%; ergonomics: 88.1% versus 74.5%; efficacy: 86.4% versus 77.5%). The self-collection approach was found to be less time consuming (23 min versus 38 min, P<0.001). The simulation model indicated that both testing approaches reduce the risk of infection and the self-collection approach tends to be slightly less effective owing to the lower sensitivity. CONCLUSIONS: The self-collection approach for SARS-CoV-2 diagnosis is technically feasible and is well rated in terms of acceptance, ergonomics, and efficacy. The simulation model facilitates the evaluation of the test effectiveness; nonetheless, considering the context specificity, appropriate adaption by the companies is required

Early reduction of SARS-CoV-2-replication in bronchial epithelium by kinin B₂ receptor antagonism.

SARS-CoV-2 has evolved to enter the host via the ACE2 receptor which is part of the kinin-kallikrein pathway. This complex pathway is only poorly understood in context of immune regulation but critical to control infection. This study examines SARS-CoV-2-infection and epithelial mechanisms of the kinin-kallikrein-system at the kinin B2 receptor level in SARS-CoV-2-infection that is of direct translational relevance. From acute SARS-CoV-2-positive study participants and -negative controls, transcriptomes of nasal curettages were analyzed. Primary airway epithelial cells (NHBEs) were infected with SARS-CoV-2 and treated with the approved B2R-antagonist icatibant. SARS-CoV-2 RNA RT-qPCR, cytotoxicity assays, plaque assays, and transcriptome analyses were performed. The treatment effect was further studied in a murine airway inflammation model in vivo. Here, we report a broad and strong upregulation of kallikreins and the kinin B2 receptor (B2R) in the nasal mucosa of acutely symptomatic SARS-CoV-2-positive study participants. A B2R-antagonist impeded SARS-CoV-2 replication and spread in NHBEs, as determined in plaque assays on Vero-E6 cells. B2R-antagonism reduced the expression of SARS-CoV-2 entry receptor ACE2, G protein-coupled receptor signaling, and ion transport in vitro and in a murine airway inflammation in vivo model. In summary, this study provides evidence that treatment with B2R-antagonists protects airway epithelial cells from SARS-CoV-2 by inhibiting its replication and spread, through the reduction of ACE2 levels and the interference with several cellular signaling processes. Future clinical studies need to shed light on the airway protection potential of approved B2R-antagonists, like icatibant, in the treatment of early-stage COVID-19. KEY MESSAGES: Induction of kinin B2 receptor in the nose of SARS-CoV-2-positive patients. Treatment with B2R-antagonist protects airway epithelial cells from SARS-CoV-2. B2R-antagonist reduces ACE2 levels in vivo and ex vivo. Protection by B2R-antagonist is mediated by inhibiting viral replication and spread

Infection control measures and prevalence of SARS-CoV-2 IgG among 4,554 University Hospital Employees, Munich, Germany.

Hospital staff are at high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the coronavirus disease (COVID-19) pandemic. This cross-sectional study aimed to determine the prevalence of SARS-CoV-2 infection in hospital staff at the University Hospital rechts der Isar in Munich, Germany, and identify modulating factors. Overall seroprevalence of SARS-CoV-2-IgG in 4,554 participants was 2.4%. Staff engaged in direct patient care, including those working in COVID-19 units, had a similar probability of being seropositive as non–patient-facing staff. Increased probability of infection was observed in staff reporting interactions with SARS-CoV-2-infected coworkers or private contacts or exposure to COVID-19 patients without appropriate personal protective equipment. Analysis of spatiotemporal trajectories identified that distinct hotspots for SARS-CoV-2-positive staff and patients only partially overlap. Patient-facing work in a healthcare facility during the SARS-CoV-2 pandemic might be safe as long as adequate personal protective equipment is used and infection prevention practices are followed inside and outside the hospital