Entwicklung eines instationären Prognosewerkzeuges zur Berechnung der Klimawandelbedingten Veränderungen der Grundwasserneubildung

Im Forschungs- und Netzwerkprojekt dynaklim untersucht die Emschergenossenschaft u. a. die wasserwirtschaftlichen Auswirkungen von klimabedingten Veränderungen des Grundwasserhaushalts in den urbanen Siedlungsgebieten. Dazu sollen mit Hilfe der vorliegenden numerischen Grundwassermodelle unter Berücksichtigung der Realisationsergebnisse des regionalen Klimamodells COSMOCLM realistische Auswirkungsszenarien und Anpassungsstrategien für die Siedlungsentwässerung abgeleitet werden. Zur Abbildung der innerjährlichen Verschiebungen der Niederschläge ist es erforderlich, die Grundwasserneubildung als ausschlaggebende Wasserhaushaltsgröße für die Modellierung instationär und flächendifferenziert zu berechnen. Da bislang keine verifizierten instationären Wasserhaushaltsmodellansätze verfügbar sind, wurde in Anlehnung an die bisher bekannten Verfahren ein geeignetes Werkzeug entwickelt, dass bei der instationären Erweiterung der stationär kalibrierten Grundwassermodelle die Massenbilanz erhält. Die damit durchgeführten stationären und instationären Nachkalibrierungen der Grundwassermodelle weisen eine gute Anpassung auf. Aus der klimatischen Bodenwasserbilanz wurden Trends bis zu den Jahren 2050 und 2100 im Emschergebiet berechnet. Im Ergebnis ist zu erwarten, dass die Grundwasserstände größeren innerjährlichen Schwankungen unterliegen werden als heute

Inconsistencies and ambiguities in liver-disease-related contraindications: a systematic analysis of SmPCs/PI of Major Drug Markets

Liver disease is a common condition worldwide that can cause alterations in drug disposition and susceptibility to drug toxicities, with increased risk of adverse drug reactions. European Summaries of Product Characteristics (SmPCs) and United States Prescribing Information (US PI) should therefore be comprehensible to prescribers regarding their liver-associated contraindications to ensure safe prescribing. This study aimed to evaluate the ambiguity of terminology used in communicating liver-associated absolute contraindications in SmPCs/PI of commonly prescribed drugs in four major drug markets (Germany, Switzerland, the United Kingdom, and the United States) by assigning wordings to different categories and analyzing their clinical comprehensibility. For US PI, 79% did not contain liver-related contraindications, compared to 2, 13, and 6% of German, Swiss, and British SmPCs, respectively. Study findings indicate that out of 228 examined SmPCs/PI containing liver-related contraindications, 77, 79, 76, and 52% contained unclear wording in the German, Swiss, British, and American drug market, respectively. Only 40% (German), 52% (Swiss), 39% (British), and 29% (American) of SmPCs/PI included terms with explicit wording. Including more precise statements in SmPCs/PI based on laboratory parameters (such as albumin) or scores (e.g., the Child–Pugh score) to objectify the severity of liver disease may improve the clarity of SmPCs/PI and the safety of drug prescription

Evidence for West Nile Virus and Usutu Virus Infections in Wild and Resident Birds in Germany, 2017 and 2018

Wild birds play an important role as reservoir hosts and vectors for zoonotic arboviruses and foster their spread. Usutu virus (USUV) has been circulating endemically in Germany since 2011, while West Nile virus (WNV) was first diagnosed in several bird species and horses in 2018. In 2017 and 2018, we screened 1709 live wild and zoo birds with real-time polymerase chain reaction and serological assays. Moreover, organ samples from bird carcasses submitted in 2017 were investigated. Overall, 57 blood samples of the live birds (2017 and 2018), and 100 organ samples of dead birds (2017) were positive for USUV-RNA, while no WNV-RNA-positive sample was found. Phylogenetic analysis revealed the first detection of USUV lineage Europe 2 in Germany and the spread of USUV lineages Europe 3 and Africa 3 towards Northern Germany. USUV antibody prevalence rates were high in Eastern Germany in both years. On the contrary, in Northern Germany, high seroprevalence rates were first detected in 2018, with the first emergence of USUV in this region. Interestingly, high WNV-specific neutralizing antibody titers were observed in resident and short-distance migratory birds in Eastern Germany in 2018, indicating the first signs of a local WNV circulation

ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

ERR articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.Peer reviewedPublisher PD

International travel-related control measures to contain the COVID-19 pandemic: a rapid review

BACKGROUND: In late 2019, the first cases of coronavirus disease 2019 (COVID‐19) were reported in Wuhan, China, followed by a worldwide spread. Numerous countries have implemented control measures related to international travel, including border closures, travel restrictions, screening at borders, and quarantine of travellers. OBJECTIVES: To assess the effectiveness of international travel‐related control measures during the COVID‐19 pandemic on infectious disease transmission and screening‐related outcomes. SEARCH METHODS: We searched MEDLINE, Embase and COVID‐19‐specific databases, including the Cochrane COVID‐19 Study Register and the WHO Global Database on COVID‐19 Research to 13 November 2020. SELECTION CRITERIA: We considered experimental, quasi‐experimental, observational and modelling studies assessing the effects of travel‐related control measures affecting human travel across international borders during the COVID‐19 pandemic. In the original review, we also considered evidence on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In this version we decided to focus on COVID‐19 evidence only. Primary outcome categories were (i) cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and subsequently full texts. For studies included in the analysis, one review author extracted data and appraised the study. At least one additional review author checked for correctness of data. To assess the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool for observational studies concerned with screening, and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed the certainty of evidence with GRADE, and several review authors discussed these GRADE judgements. MAIN RESULTS: Overall, we included 62 unique studies in the analysis; 49 were modelling studies and 13 were observational studies. Studies covered a variety of settings and levels of community transmission. Most studies compared travel‐related control measures against a counterfactual scenario in which the measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of stringency of the measures (including relaxation of restrictions), or a combination of measures. Concerns with the quality of modelling studies related to potentially inappropriate assumptions about the structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to the selection of travellers and the reference test, and unclear reporting of certain methodological aspects. Below we outline the results for each intervention category by illustrating the findings from selected outcomes. Travel restrictions reducing or stopping cross‐border travel (31 modelling studies) The studies assessed cases avoided and shift in epidemic development. We found very low‐certainty evidence for a reduction in COVID‐19 cases in the community (13 studies) and cases exported or imported (9 studies). Most studies reported positive effects, with effect sizes varying widely; only a few studies showed no effect. There was very low‐certainty evidence that cross‐border travel controls can slow the spread of COVID‐19. Most studies predicted positive effects, however, results from individual studies varied from a delay of less than one day to a delay of 85 days; very few studies predicted no effect of the measure. Screening at borders (13 modelling studies; 13 observational studies) Screening measures covered symptom/exposure‐based screening or test‐based screening (commonly specifying polymerase chain reaction (PCR) testing), or both, before departure or upon or within a few days of arrival. Studies assessed cases avoided, shift in epidemic development and cases detected. Studies generally predicted or observed some benefit from screening at borders, however these varied widely. For symptom/exposure‐based screening, one modelling study reported that global implementation of screening measures would reduce the number of cases exported per day from another country by 82% (95% confidence interval (CI) 72% to 95%) (moderate‐certainty evidence). Four modelling studies predicted delays in epidemic development, although there was wide variation in the results between the studies (very low‐certainty evidence). Four modelling studies predicted that the proportion of cases detected would range from 1% to 53% (very low‐certainty evidence). Nine observational studies observed the detected proportion to range from 0% to 100% (very low‐certainty evidence), although all but one study observed this proportion to be less than 54%. For test‐based screening, one modelling study provided very low‐certainty evidence for the number of cases avoided. It reported that testing travellers reduced imported or exported cases as well as secondary cases. Five observational studies observed that the proportion of cases detected varied from 58% to 90% (very low‐certainty evidence). Quarantine (12 modelling studies) The studies assessed cases avoided, shift in epidemic development and cases detected. All studies suggested some benefit of quarantine, however the magnitude of the effect ranged from small to large across the different outcomes (very low‐ to low‐certainty evidence). Three modelling studies predicted that the reduction in the number of cases in the community ranged from 450 to over 64,000 fewer cases (very low‐certainty evidence). The variation in effect was possibly related to the duration of quarantine and compliance. Quarantine and screening at borders (7 modelling studies; 4 observational studies) The studies assessed shift in epidemic development and cases detected. Most studies predicted positive effects for the combined measures with varying magnitudes (very low‐ to low‐certainty evidence). Four observational studies observed that the proportion of cases detected for quarantine and screening at borders ranged from 68% to 92% (low‐certainty evidence). The variation may depend on how the measures were combined, including the length of the quarantine period and days when the test was conducted in quarantine. AUTHORS' CONCLUSIONS: With much of the evidence derived from modelling studies, notably for travel restrictions reducing or stopping cross‐border travel and quarantine of travellers, there is a lack of 'real‐world' evidence. The certainty of the evidence for most travel‐related control measures and outcomes is very low and the true effects are likely to be substantially different from those reported here. Broadly, travel restrictions may limit the spread of disease across national borders. Symptom/exposure‐based screening measures at borders on their own are likely not effective; PCR testing at borders as a screening measure likely detects more cases than symptom/exposure‐based screening at borders, although if performed only upon arrival this will likely also miss a meaningful proportion of cases. Quarantine, based on a sufficiently long quarantine period and high compliance is likely to largely avoid further transmission from travellers. Combining quarantine with PCR testing at borders will likely improve effectiveness. Many studies suggest that effects depend on factors, such as levels of community transmission, travel volumes and duration, other public health measures in place, and the exact specification and timing of the measure. Future research should be better reported, employ a range of designs beyond modelling and assess potential benefits and harms of the travel‐related control measures from a societal perspective

Germline Polymorphisms in MGMT Associated With Temozolomide-Related Myelotoxicity Risk in Patients With Glioblastoma Treated on NRG Oncology/RTOG 0825

Background: We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma. Methods: Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity. Results: 23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; 30 stopped treatment due to toxicity. Among those who continued therapy (n = 26), 11 experienced myelotoxicity again. The final multivariable clinical factor model included treatment arm, gender, and anticonvulsant status and had low prediction accuracy (area under the curve [AUC] = 0.672). The final extended risk prediction model including four polymorphisms in MGMT had better prediction (AUC = 0.827). Receiving combination chemotherapy (OR, 1.82; 95% CI, 1.02-3.27) and being female (OR, 4.45; 95% CI, 2.45-8.08) significantly increased myelotoxicity risk. For each additional minor allele in the polymorphisms, the risk increased by 64% (OR, 1.64; 95% CI, 1.43-1.89). Conclusions: Myelotoxicity during concurrent chemoradiation with temozolomide is an uncommon but serious event, often leading to treatment cessation. Successful prediction of toxicity may lead to more cost-effective individualized monitoring of at-risk subjects. The addition of genetic factors greatly enhanced our ability to predict toxicity among a group of similarly treated glioblastoma patients

Klimawandel-bedingte Veränderungen der Grundwasserneubildung im urbanen Raum am Beispiel des Emschergebietes

Im Forschungs- und Netzwerkprojekt dynaklim untersucht die Emschergenossenschaft u. a. die wasserwirtschaftlichen Auswirkungen von klimabedingten Veränderungen des Grundwasserhaushalts in den urbanen Siedlungsgebieten. Dazu sollen mit Hilfe der vorliegenden numerischen Grundwassermodelle unter Berücksichtigung der Realisationsergebnisse des regionalen Klimamodells COSMOCLM realistische Auswirkungsszenarien und Anpassungsstrategien für die Siedlungsentwässerung abgeleitet werden. Zur Abbildung der innerjährlichen Verschiebungen der Niederschläge ist es erforderlich, die Grundwasserneubildung als ausschlaggebende Wasserhaushaltsgröße für die Modellierung instationär und flächendifferenziert zu berechnen. Da bislang keine verifizierten instationären Wasserhaushaltsmodellansätze verfügbar sind, wurde in Anlehnung an die bisher bekannten Verfahren ein geeignetes Werkzeug entwickelt, dass bei der instationären Erweiterung der stationär kalibrierten Grundwassermodelle die Massenbilanz erhält. Die flächendifferenzierte Grundwasserneubildung für das Einzugsgebiet der Emscher für die Zeitschnitte 1961-1990, 2021-2050 und 2071-2100 wurde berechnet und die Ergebnisse auf Teileinzugsgebietsebene analysiert. Aus der klimatischen Bodenwasserbilanz wurden Trends bis zu den Jahren 2050 und 2100 im Emschergebiet berechnet