Reiseassoziierte COVID-19-Fälle im Stadtkreis Offenbach und Deutschland, Juni – November 2020: Erkrankungsbeginne und SARS-CoV-2-Testungen nach Einreise

Um den Einfluss von reiseassoziierten COVID-19-Fällen auf das lokale In¬fektionsgeschehen in Deutschland zu verstehen, ist eine kontinuierliche Bewertung der Fallzahlen unter Berücksichtigung der Reisetätigkeit, Quarantäne- und Teststrategie, notwendig. Quarantäne und Tests nach der Einreise nach Deutschland sollen die Wahrscheinlichkeit einer SARS-CoV-2-Übertragung verringern. Daten aus dem Stadtkreis Offenbach geben Hinweise darauf, dass Personen nach der Einreise häufig erst innerhalb von fünf Tagen Symptome zeigten und das symp¬tombasierte Screenings bei Einreise somit nur ei¬nen kleinen Anteil der Fälle erkennen würde. Es bleibt wichtig zu kommunizieren, dass ein ne¬gativer Test falsche Sicherheit vermitteln kann und dass Personen sich bei Auftreten von mit COVID-19 vereinbaren Symptomen erneut testen und absondern müssen.Peer Reviewe

New instruments of administrative procedure in Germany? : between acceptance and mediation

Disturbance of intestinal wound closure leads to insufficient anastomotic healing and is associated with considerable morbidity following colorectal resections. Matrix metalloproteinases (MMPs) play a crucial role in regulation of wound closure. Here fluorescence endoscopy was evaluated for assessment of MMP-2/-9 expression during failed intestinal anastomotic healing.Distal colonic anastomoses were performed as a model for disturbed healing in 36 Balb/c mice. Healing was evaluated endoscopically, macroscopically, and histologically after 1, 3 and 5 days. For detection of MMP-2/-9 expression fluorescence endoscopy (FE) was used following i.v.-administration of a Cy5.5-labeled MMP-2/-9 specific tracer. FE was complemented by quantification of the fluorescence signal using the MS-FX PRO Optical Imaging System. An overall leakage score was calculated and correlated with the results of FE.With increasing incidence of anastomotic leakage from POD1 (17%) to POD5 (83%) the uptake of the MMP tracer gradually increased (signal-to-noise ratio (SNR), POD1: 17.91 ± 1.251 vs. POD3: 30.56 ± 3.03 vs. POD5: 44.8 ± 4.473, P<0.0001). Mice with defective anastomotic healing showed significantly higher uptake compared to non-defective (SNR: 37.37± 3.63 vs. 26.16± 3.635, P = 0.0369). White light endoscopy and FE allowed evaluation of anastomotic healing and visualization of mucosal MMPs in vivo. Using FE based detection of MMPs in the anastomosis, an overall positive predictive value of 71.4% and negative predictive value of 66.6% was calculated for detection of anastomotic leakage.During disturbed anastomotic healing increased expression of MMP-2/-9 was observed in the anastomotic tissue. Fluorescence endoscopy for detection of MMP-2/-9 during the healing process might be a promising tool for early identification of anastomotic leakage

Two Distinct Coagulase-Dependent Barriers Protect Staphylococcus aureus from Neutrophils in a Three Dimensional in vitro Infection Model

Staphylococcus aureus is a pyogenic abscess-forming facultative pathogenic microorganism expressing a large set of virulence-associated factors. Among these, secreted proteins with binding capacity to plasma proteins (e.g. fibrinogen binding proteins Eap and Emp) and prothrombin activators such as Coagulase (Coa) and vWbp are involved in abscess formation. By using a three-dimensional collagen gel (3D-CoG) supplemented with fibrinogen (Fib) we studied the growth behavior of S. aureus strain Newman and a set of mutants as well as their interaction with mouse neutrophils by real-time confocal microscopy. In 3D-CoG/Fib, S. aureus forms microcolonies which are surrounded by an inner pseudocapsule and an extended outer dense microcolony-associated meshwork (MAM) containing fibrin. Coa is involved in formation of the pseudocapsule whereas MAM formation depends on vWbp. Moreover, agr-dependent dispersal of late stage microcolonies could be observed. Furthermore, we demonstrate that the pseudocapsule and the MAM act as mechanical barriers against neutrophils attracted to the microcolony. The thrombin inhibitor argatroban is able to prevent formation of both pseudocapsule and MAM and supports access of neutrophils to staphylococci. Taken together, this model can simulate specific stages of S. aureus abscess formation by temporal dissection of bacterial growth and recruitment of immune cells. It can complement established animal infection models in the development of new treatment options

The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis

BACKGROUND: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. METHODS: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251. FINDINGS: Between March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (-2·22, -2·98 to -1·45, Cohen's d=0·19; p<0·0001), and hallucinations (-1·58, -1·98 to -1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported. INTERPRETATION: To our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision. FUNDING: Wellcome Trust

Suicide trends in the early months of the COVID-19 pandemic: an interrupted time-series analysis of preliminary data from 21 countries

BackgroundThe COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that at its most extreme, this may manifest itself in increased suicide rates.MethodsWe sourced real-time suicide data from around the world via a systematic internet search and recourse to our networks and the published literature. We used interrupted time series analysis to model the trend in monthly suicides prior to COVID-19 in each country/area-within-country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic. Countries/areas-within countries contributed data from at least 1 January 2019 to 31 July 2020 and potentially from as far back as 1 January 2016 until as recently as 31 October 2020. We conducted a primary analysis in which we treated 1 April to 31 July 2020 as the COVID-19 period, and two sensitivity analyses in which we varied its start and end dates (for those countries/areas-within-countries with data beyond July 2020).OutcomesWe sourced data from 21 countries (high income [n=16], upper-middle income [n=5]; whole country [n=10], area(s)-within-the-country [n=11]). In general, there does not appear to have been a significant increase in suicides since the pandemic began in the countries for which we had data. In fact, in a number of countries/areas-within-countries there appears to have been a decrease.InterpretationThis is the first study to examine suicides occurring in the context of the COVID-19 pandemic in multiple countries. It offers a consistent picture, albeit from high- and upper-middle income countries, of suicide numbers largely remaining unchanged or declining in the early months of the pandemic. We need to remain vigilant and be poised to respond if the situation changes as the longer-term mental health and economic impacts of the pandemic unfold

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Second Survey on Patient-centred Care of Ocular Graft-versus-Host Disease in Germany

Background graft-versus-host disease (GvHD) is a common complication after allogeneic haematopoietic stem cell transplantation (allo-SCT) and causes immunological rejection of host tissues, which can occur both acute or chronically. Approximately 40-80% of patients with the diagnosis of chronic GvHD (cGvHD) also develop ocular GvHD. For these patients, immediate and uncomplicated access to interdisciplinary patient-centred care is important. We performed this survey to improve understanding of the structure of patient-centred care in Germany. Methods The GvHD working party of the Cornea Section of the German Society of Ophthalmology sent the Survey of ocular GvHD 2016 to all university and specialised hospitals in Germany. We evaluated the data and compared the information with survey results from 2014, in order to draw conclusions about the structure and process of patient-centred care in ocular GvHD. Besides the questions from 2014 on the numbers of allo-SCT, frequency of examinations, etc. there were additional questions on the prescription of ciclosporin and autologous serum eye drops. The question on frequency examination was further expanded to include examinations of paediatric patients. Results Of 30 participating hospitals, 22 had already taken part in the first survey. According to the information they provided, approx. 1860 allo-SCTs were performed in the transplantation units of the participating eye hospitals in 2016. This was more than half of the transplantations performed in Germany. Ophthalmologists examined between 2 and 250 Patients per year per centre. Eight clinics provide a specialised outpatient clinic for ocular GvHD. Nearly all the participating clinics prescribe ciclosporin eye drops. About 2/3 provide autologous serum eye drops, seven obtain them from external sources. Overall approx. 125- 140 children were examined in 2016. Conclusions Due to the potential severity of ocular GvHD with immobilisation of the patients and the imminent loss of sight, further improvements in eye care are required. For example, offers such as special consultations, with expertise located close to any transplantation unit are recommended. This requires in particular ophthalmologists to participate in the patient care to enhance quality of life after allo-SCT. In summary, we conclude that the present structures are not sufficient to treat all patients suffering from ocular GvHD in Germany, but the situation has evidently improved

Messung von schmerzbezogener Erlebensvermeidung: Analyse des Acceptance and Action Questionnaire-II-Pain bei Patienten mit chronischem Schmerz

Einleitung und Fragestellung: Erlebensvermeidung ('experiential avoidance') stellt einen zentralen störungsrelevanten Prozess im Rahmen der Akzeptanz- und Commitment-Therapie (ACT) dar. Zur Erfassung wurde der 'Acceptance and Action Questionnaire II' (AAQ-II) entwickelt und in den Niederlanden für eine Patientengruppe mit chronischem Schmerz adaptiert und validiert (AAQ-II-P). Hohe Werte im AAQ-II-P bedeuten hohe schmerzbezogene Erlebensvermeidung. Ziel der vorgestellten Untersuchung ist die Erfassung von schmerzbezogener Erlebensvermeidung mit einer deutschen Version des AAQ-II-P bei chronischen Schmerzpatienten und die Prüfung psychometrischer Merkmale des Messverfahrens. Methodik: Der AAQ-II wurde mittels eines Vorwärts-Rückwärts-Verfahrens ins Deutsche übersetzt, für chronischen Schmerz adaptiert (AAQ-II-P) und von 168 Patienten einer universitären Schmerzambulanz beantwortet. Zusätzlich wurden Daten zu schmerzbedingter Beeinträchtigung (CPG: Schweregrad nach von Korff) und Schmerzkatastrophisieren (PCS) erhoben sowie zu gesundheitsbezogener Lebensqualität (SF-12), Angst und Depressivität (HADS-D). Ebenfalls erfasst wurden allgemeine Persönlichkeitsmerkmale (BFI-K) und habituelle Achtsamkeit (KIMSS). Ausgewertet wurden Reliabilität und faktorielle Validität des AAQ-II-P sowie seine Beziehung zu den anderen psychometrischen Verfahren. Ergebnisse: Der AAQ-II-P erzielte eine hohe interne Konsistenz mit alpha= 0,89 sowie eine eindimensionale Faktorenstruktur mit 61 % aufgeklärter Varianz. Geringe Korrelationen ergaben sich zu Persönlichkeitsdimensionen (maximal r= 0,44 zu Neurotizismus) und Achtsamkeit (maximal r= -0,43 zu Akzeptanz). Ein hoher Zusammenhang fand sich zu Schmerzkatastrophisieren (r= 0,75), Depression (r= 0,73) und Angst (r= 0,66). Die Beziehung zu Lebensqualität war am stärksten ausgeprägt auf der Psychischen Summenskala (r= -0,58). Diskussion und Schlussfolgerung: Die deutsche Version des AAQ-II-P hat eine gute Reliabilität und weist hinsichtlich Zuverlässigkeit und Faktorenstruktur hohe Vergleichbarkeit mit der Originalversion auf. Die Beziehungen zu den Skalen der psychometrischen Verfahren sind zumeist in erwarteter Richtung und Höhe. Patienten mit chronischem Schmerz und hoher schmerzbezogener Erlebensvermeidung tendieren deutlich zum Schmerzkatastrophisieren und zeichnen sich durch schlechtere psychische Lebensqualität aus. Dies spricht für die Relevanz des Konstrukts hinsichtlich therapeutischer Zielvariablen