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In September 2018, monkeypox virus was transmitted from a patient to a healthcare worker in the United Kingdom. Transmission was probably through contact with contaminated bedding. Infection control precautions for contacts (vaccination, daily monitoring, staying home from work) were implemented. Of 134 potential contacts, 4 became ill; all patients survived.

Anticorrosive organic coatings are usually tested with accelerated weathering methods to assess their anticorrosive performance. The results of lab testing often do not correlate well with results from field testing, which resembles the conditions of actual use more closely. We tested the correlation of the neutral salt spray test (NSS, ISO 9227) and tests for mechanical properties and a 5-year field exposure in four different locations in the atmospheric zone, splash zone and immersion zone using 19 organic coatings for hydraulic steelwork. No correlation was found between the anticorrosive performance under outdoor exposure and the mechanical properties of a coating. The NSS test showed a positive correlation with the results in the field in 6 of 12 cases. For the fresh water testing location in Trier, the correlation proved to be very good. The biggest difference between lab and field testing was observed for zinc-primer-free coatings, which passed in the lab testing and failed in the outdoor testing. This study shows that the NSS test correlates with outdoor exposure only in some cases on a statistically significant level, but the results of NSS testing can be useful in approval testing for protective coating systems using predefined pass/fail criteria.

Risk assessment before interventions in elderly patients becomes more and more vital due to an increasing number of elderly patients requiring surgery. Existing risk scores are often not tailored to marginalized groups such as patients aged 80 years or older. We aimed to develop an easy-to-use and readily applicable risk assessment tool that implements pre-interventional predictors of 30-day mortality in elderly patients (≥80 years) undergoing interventions under anesthesia. Using Cox regression analysis, we compared different sets of predictors by taking into account their ease of availability and by evaluating predictive accuracy. Coefficient estimates were utilized to set up a scoring system that was internally validated. Model building and evaluation were based on data from the Peri-Interventional Outcome Study in the Elderly (POSE), which was conducted as a European multicenter, observational prospective cohort study. Our risk assessment tool, named PIRATE, contains three predictors assessable at admission (urgency , severity and living conditions ). Discriminatory power, as measured by the concordance index, was 0.75. The estimated prediction error, as measured by the Brier score, was 0.036 (covariate-free reference model: 0.043). PIRATE is an easy-to-use risk assessment tool that helps stratifying elderly patients undergoing interventions with anesthesia at increased risk of mortality. PIRATE is readily available and applies to a wide variety of settings. In particular, it covers patients needing elective or emergency surgery and undergoing in-hospital or day-case surgery. Also, it applies to all types of interventions, from minor to major. It may serve as a basis for multidisciplinary and informed shared decision-making.

Background With progress on both the theoretical and the computational fronts the use of spline modelling has become an established tool in statistical regression analysis. An important issue in spline modelling is the availability of user friendly, well documented software packages. Following the idea of the STRengthening Analytical Thinking for Observational Studies initiative to provide users with guidance documents on the application of statistical methods in observational research, the aim of this article is to provide an overview of the most widely used spline-based techniques and their implementation in R. Methods In this work, we focus on the R Language for Statistical Computing which has become a hugely popular statistics software. We identified a set of packages that include functions for spline modelling within a regression framework. Using simulated and real data we provide an introduction to spline modelling and an overview of the most popular spline functions. Results We present a series of simple scenarios of univariate data, where different basis functions are used to identify the correct functional form of an independent variable. Even in simple data, using routines from different packages would lead to different results. Conclusions This work illustrate challenges that an analyst faces when working with data. Most differences can be attributed to the choice of hyper-parameters rather than the basis used. In fact an experienced user will know how to obtain a reasonable outcome, regardless of the type of spline used. However, many analysts do not have sufficient knowledge to use these powerful tools adequately and will need more guidance.

Background/AimsAge-related macular degeneration (AMD) is the main cause of visual impairment and blindness in Europe. A further increase in the number of affected persons is expected and current European data are needed for healthcare resource planning.MethodsWe performed a systematic review on the prevalence and incidence of AMD based on the meta-analysis of observational studies in epidemiology guideline. Meta-analysis and meta-regression on time-trends, age, countries, regions, sex and classification systems for AMD were performed. Based on Eurostat population projections, the pooled prevalence estimates were extrapolated to the year 2050.ResultsTwenty-two prevalence and four incidence studies published since 1996 were included. Our pooled prevalence estimate of early or intermediate AMD and any late AMD in those 60 years and older was 25.3% (95% CI 18.0% to 34.4%) and 2.4% (95% CI 1.8% to 3.3%), respectively. A significant increase in prevalence was seen in older populations. In the meta-analysis of incidence, the pooled annual incidence of any late AMD was 1.4 per 1 000 individuals (95% CI 0.8 to 2.6). Overall, the number of EU inhabitants with any AMD is expected to increase from 67 to 77 million until 2050. Incident late AMD is estimated to increase from 400 000 per year today to 700 000 per year in 2050.ConclusionsApproximately 67 million people in the EU are currently affected by any AMD and, due to population ageing, this number is expected to increase by 15% until 2050. Monitoring and treatment of people with advanced disease stages will require additional healthcare resources and thorough healthcare planning in the years and decades to come.

The development of molecular signatures for the prediction of time-to-event outcomes is a methodologically challenging task in bioinformatics and biostatistics. Although there are numerous approaches for the derivation of marker combinations and their evaluation, the underlying methodology often suffers from the problem that different optimization criteria are mixed during the feature selection, estimation and evaluation steps. This might result in marker combinations that are suboptimal regarding the evaluation criterion of interest. To address this issue, we propose a unified framework to derive and evaluate biomarker combinations. Our approach is based on the concordance index for time-to-event data, which is a non-parametric measure to quantify the discriminatory power of a prediction rule. Specifically, we propose a gradient boosting algorithm that results in linear biomarker combinations that are optimal with respect to a smoothed version of the concordance index. We investigate the performance of our algorithm in a large-scale simulation study and in two molecular data sets for the prediction of survival in breast cancer patients. Our numerical results show that the new approach is not only methodologically sound but can also lead to a higher discriminatory power than traditional approaches for the derivation of gene signatures.

Background There is growing evidence that antibody responses play a role in the resolution of SARS-CoV-2 infection. Patients with primary or secondary antibody deficiency are at increased risk of persistent infection. This challenging clinical scenario is associated with adverse patient outcome and potentially creates an ecological niche for the evolution of novel SARS-CoV-2 variants with immune evasion capacity. Case reports and/or series have implied a therapeutic role for convalescent plasma (CP) to secure virological clearance, although concerns have been raised about the effectiveness of CP and its potential to drive viral evolution, and it has largely been withdrawn from clinical use in the UK. Case presentation We report two cases in which persistent SARS-CoV-2 infection was cleared following administration of the monoclonal antibody combination casirivimab and imdevimab (REGN-COV2, Ronapreve). A 55-year-old male with follicular lymphoma, treated with B cell depleting therapy, developed SARS-CoV-2 infection in September 2020 which then persisted for over 200 days. He was hospitalised on four occasions with COVID-19 and suffered debilitating fatigue and malaise throughout. There was no clinical response to antiviral therapy with remdesivir or CP, and SARS-CoV-2 was consistently detected in nasopharyngeal swabs. Intrahost evolution of several spike variants of uncertain significance was identified by viral sequence analysis. Delivery of REGN-COV2, in combination with remdesivir, was associated with clinical improvement and viral clearance within 6 days, which was sustained for over 150 days despite immunotherapy for relapsed follicular lymphoma. The second case, a 68-year-old female with chronic lymphocytic leukaemia on ibrutinib, also developed persistent SARS-CoV-2 infection. Despite a lack of response to remdesivir, infection promptly cleared following REGN-COV2 in combination with remdesivir, accompanied by resolution of inflammation and full clinical recovery that has been maintained for over 290 days. Conclusions These cases highlight the potential benefit of REGN-COV2 as therapy for persistent SARS-CoV-2 infection in antibody deficient individuals, including after failure of CP treatment. Formal clinical studies are warranted to assess the effectiveness of REGN-COV2 in antibody-deficient patients, especially in light of the emergence of variants of concern, such as Omicron, that appear to evade REGN-COV2 neutralisation.

Over the past 25 years, numerous studies have evaluated triage system performance, but longitudinal data are limited. This study is the first to assess the Manchester Triage System (MTS) over a decade to determine the accuracy of initial patient assessments and system stability under external influences such as staff turnover, health policy changes, demographic shifts, and the COVID-19 pandemic. We conducted a large-scale, monocentric, retrospective observational study at a tertiary care hospital. Between 2014 and 2023 a total of 355,135 emergency patients were included. Average age increased from 48.1 to 52.1 years. The distribution of the five MTS urgency levels remained stable. Prediction of hospital admission (AUC 0.719-0.756) and ICU admission (AUC 0.831-0.862) was consistent throughout the period. Twelve-hour survival probabilities were above 0.99 for \"blue\" to \"orange\" patients and above 0.89 for \"red\" patients. Short-term mortality prediction (AUC) ranged from 0.845 to 0.894. Thirty-day survival remained >0.8 for \"blue\" to \"orange\" stages, while the \"red\" stage declined from 0.63 (2014) to 0.44 (2023). The AUC for 30-day mortality increased from 0.672 to 0.750 over the decade. Construct validity assessment demonstrates that the MTS reliably assigns appropriate urgency levels to incoming emergency patients. Longitudinal evaluation shows that its accuracy remained stable over ten years despite high staff turnover, health policy and demographic changes, and the COVID-19 pandemic. These findings confirm the robustness and reliability of the MTS in a high-volume tertiary care setting and support its continued use for emergency patient prioritization.

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values >0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials. Plasma extracellular vesicles contain quantifiable amounts of TDP-43 and full-length tau, allowing the accurate assessment of pathology in frontotemporal dementia, frontotemporal dementia spectrum disorders and amyotrophic lateral sclerosis.