Prevention of hospital infections by intervention and training (PROHIBIT): results of a pan-European cluster-randomized multicentre study to reduce central venous catheter-related bloodstream infections

Purpose

To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators.

Methods

Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance.

Results

Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions.

Conclusions

This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.

     

Accurate detection of stent-graft migration in a pulsatile aortic model using Roentgen stereophotogrammetric analysis.

PURPOSE: To evaluate the feasibility and accuracy of Roentgen stereophotogrammetric analysis (RSA) versus computed tomography (CT) for detecting stent-graft migration in an in vitro pulsatile circulation model and to study the feasibility of a nitinol endovascular clip (NEC) as an aortic wall reference marker for RSA. METHODS: An aortic model with stent-graft was constructed and connected to an artificial circulation with a physiological flow and pressure profile. Tantalum markers and NECs were used as aortic reference markers for RSA analysis. Stent-graft migrations were measured during pulsatile circulation with RSA and CT. CT images acquired with 64 x 0.5-mm beam collimation were analyzed with Vitrea postprocessing software using a standard clinical protocol and central lumen line reconstruction. RSA in the model with the circulation switched off was used as the reference standard to determine stent-graft migration. The measurement errors of RSA and CT were determined during pulsatile circulation. RESULTS: The mean measurement error +/- standard deviation (maximum) of RSA during pulsatile circulation using the tantalum markers was -0.5+/-0.16 (0.7) mm. Using the NEC, the mean (maximum) measurement error was -0.4+/-0.25 (1.1) mm. The mean (maximum) measurement error of CT was -1.1+/-1.17 (2.8) mm. CONCLUSION: RSA is an accurate and feasible tool to measure stent-graft migration in a pulsatile environment. Migration measurement with RSA was more accurate than CT in this experimental setup. The nitinol clip tested in this study is potentially feasible as an aortic reference marker in patients after endovascular repair.     

Das Gehen ist der Weg

Zusammenfassung In diesem Beitrag wird der Unterschied zwischen Selbsterfahrung und Selbstreflexion anhand konstruktivistischer Überlegungen diskutiert. Weiter wird die Bedeutung und Entwicklung der Familienrekonstruktion im Rahmen der Ausbildung am Institut für Familientherapie, Ausbildung und Entwicklung e.V., Weinheim, beschrieben. Systemisches Denken und Handeln in und mit Gruppen sowie das “Leitungsverständnis" des Lehrtherapeuten werden thematisiert. Summary In this article the author discusses the differences between self-encounter and self-reflection by using constructivist ideas. Further on, the significance and development of family reconstruction in the context of training at the "Institut für Familientherapie, Ausbildung und Entwicklung e.V., Weinheim," are described. Systemic thinking and acting in and with groups as well as the concept of leading a group are pointed out.     

The significance of angiogenesis in malignant pheochromocytomas

The purpose of this study was to investigate tumor angiogenesis in a series of benign and malignant pheochromocytomas and to determine whether there is a correlation between angiogenesis and the presence of distant metastases. In this study, the CD31 monoclonal antibody was selected to measure intratumoral microvessel density. Nineteen patients with malignant pheochromocytomas and nineteen patients with benign pheochromocytomas who underwent operation were studied. In order to quantify intratumoral microvessel density, the total number of pixels of CD31-positive reactivity was assessed and expressed as a percentage of the total tissue area in the analyzed field. Analysis of variance revealed a statistically significant correlation between malignancy and intratumoral microvessel density (p=0.0009). Although there was a considerable variability in the intratumoral microvessel density from tumor to tumor within both the benign and the malignant group, a percentage of more than 28.5% anti-CD31 stained area was found only in malignant tumors. In conclusion, this study shows that the mean intratumoral microvessel density in malignant pheochromocytomas is increased approximately two-fold as compared with benign tumors. However, the clinical significance of this prognostic marker is rather weak, because only 4 of the 19 malignant pheochromocytomas had microvesel density higher than this threshold of 28.5%.     

Hypoplastic left heart syndrome with intact atrial septum associated with deletion of the short arm of chromosome 18.

We report on a female newborn with deletion of the short arm of the chromosome 18 (del 18p) and hypoplastic left heart syndrome (HLHS) with intact atrial septum. Several forms of congenital heart disease (CHD) are found in 10% of patients with this chromosomal abnormality, although HLHS has not been reported yet. Interesting coronary artery anomalies, as well as the presence of pulmonary lymphangiectasia, were found in our patient and were contributors to her fatal outcome. Del 18 p must be considered when evaluating a patient with characteristic phenotypical anomalies and HLHS with intact atrial septum.     

Epidemiologische Ansätze zur Klärung wichtiger Forschungsfragen zu COVID-19 – eine Übersicht

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Epidemiologie als wissenschaftliche Disziplin ist prädestiniert dafür, Kernfragen der COVID-19-Pandemie zu...     

Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland

The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a United Kingdom MRSA database containing over 1000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland, and the Republic of Ireland over a decade. We sequenced 1013 MRSA submitted to the British Society for Antimicrobial Chemotherapy by 46 laboratories between 2001 and 2010. Each isolate was assigned to a regional healthcare referral network in England and was otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualize MRSA outbreak investigations and to detect the spread of resistance. The majority of isolates (n = 783, 77%) belonged to CC22, which contains the dominant United Kingdom epidemic clone (EMRSA-15). There was marked geographic structuring of EMRSA-15, consistent with widespread dissemination prior to the sampling decade followed by local diversification. The addition of MRSA genomes from two outbreaks and one pseudo-outbreak demonstrated the certainty with which outbreaks could be confirmed or refuted. We identified local and regional differences in antibiotic resistance profiles, with examples of local expansion, as well as widespread circulation of mobile genetic elements across the bacterial population. We have generated a resource for the future surveillance and outbreak investigation of MRSA in the United Kingdom and Ireland and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance.Methicillin-resistant Staphylococcus aureus (MRSA) was first isolated in 1961 in the United Kingdom (UK), 1 yr after methicillin was introduced into clinical practice (Jevons 1961). The prevalence of MRSA gradually increased thereafter, and by 1971, 5% of S. aureus isolates referred to the National Staphylococcal Reference Laboratory were MRSA (Marples and Reith 1992). Outbreaks of gentamicin-resistant MRSA in several hospitals during the late 1970s (Shanson 1981) were followed by the emergence of MRSA with potential for epidemic spread (Johnson et al. 2005). By the mid-1980s, MRSA had spread across the UK, and the majority were epidemic (E)MRSA-1, later assigned as sequence type (ST) 239 by multilocus sequence typing (MLST) (Kerr et al. 1990; Johnson et al. 2005). A decline in EMRSA-1 in the late 1980s and early 1990s was associated with an increase in EMRSA-3 (ST 5) (Marples and Reith 1992; Richardson and Reith 1993; Cox et al. 1995; Enright et al. 2002). This dynamic process continued with the emergence in the early 1990s of EMRSA-15 (ST 22) and EMRSA-16 (ST 36) (Richardson and Reith 1993; Cox et al. 1995; Enright et al. 2002), which disseminated across the UK. These two clones continue to predominate, with EMRSA-15 accounting for ∼85% of MRSA bloodstream infections in the UK in 2007 and with trends suggesting that EMRSA-16 is in decline (Ellington et al. 2010; McAdam et al. 2012). Antimicrobial resistance is known to differ between EMRSA-15 and -16, with EMRSA-16 being the more resistant lineage of the two. However, for both lineages, the acquisition of the SCCmec element conferring methicillin resistance and the presence of mutations in gyrA and grlA conferring fluoroquinolone resistance are considered to be major contributors to the success of these epidemic lineages (Knight et al. 2012; McAdam et al. 2012; Holden et al. 2013).Bacterial genotyping using pulsed-field gel electrophoresis (PFGE), MLST, and spa typing has been used to identify epidemic clones and to give insights into the microevolutionary dynamics of predominant MRSA lineages in the UK. However, these methods have limited resolution and lack discriminatory power when one or a small number of clones predominate (McAdam et al. 2012; Miller et al. 2014; Bartels et al. 2015). This means that once widely established, the subsequent dynamics of clonal MRSA spread within and between healthcare facilities cannot be fully elucidated. As a result, bacterial typing does not form a central component of MRSA transmission and outbreak investigation. Several recent publications have confirmed the ability of whole-genome sequencing (WGS) to define transmission dynamics of a single clone at different geographic and temporal scales. This has identified global and local transmission routes and, when combined with epidemiological data, can confirm or refute putative MRSA outbreaks (Köser et al. 2012; Harris et al. 2013; Nubel et al. 2013; Miller et al. 2014; Török et al. 2014; Bartels et al. 2015). Similarly, while surveillance of MRSA has been carried over several years and a limited number of point prevalence studies of variable methodology have been undertaken in different settings, serial systematic prevalence studies of individual epidemic lineages are lacking (Johnson et al. 2012; Afshinnekoo et al. 2015; Bartels et al. 2015; Peng et al. 2015). WGS could potentially be used for national and local surveillance of MRSA lineages and to enhance the investigation of suspected outbreaks, but comprehensive genomic databases are required to provide the context that would allow robust epidemiological interferences. Here, we describe the analysis of over 1000 MRSA genomes drawn from across the UK and Ireland over a period of a decade and the first evaluation of this rich data set to describe the macroepidemiology of MRSA.     

Ethylmercury and Hg2+ induce the formation of neutrophil extracellular traps (NETs) by human neutrophil granulocytes

Humans are exposed to different mercurial compounds from various sources, most frequently from dental fillings, preservatives in vaccines, or consumption of fish. Among other toxic effects, these substances interact with the immune system. In high doses, mercurials are immunosuppressive. However, lower doses of some mercurials stimulate the immune system, inducing different forms of autoimmunity, autoantibodies, and glomerulonephritis in rodents. Furthermore, some studies suggest a connection between mercury exposure and the occurrence of autoantibodies against nuclear components and granulocyte cytoplasmic proteins in humans. Still, the underlying mechanisms need to be clarified. The present study investigates the formation of neutrophil extracellular traps (NETs) in response to thimerosal and its metabolites ethyl mercury (EtHg), thiosalicylic acid, and mercuric ions (Hg²⁺). Only EtHg and Hg²⁺ triggered NETosis. It was independent of PKC, ERK1/2, p38, and zinc signals and not affected by the NADPH oxidase inhibitor DPI. Instead, EtHg and Hg²⁺ triggered NADPH oxidase-independent production of ROS, which are likely to be involved in mercurial-induced NET formation. This finding might help understanding the autoimmune potential of mercurial compounds. Some diseases, to which a connection with mercurials has been shown, such as Wegener’s granulomatosis and systemic lupus erythematosus, are characterized by high prevalence of autoantibodies against neutrophil-specific auto-antigens. Externalization in the form of NETs may be a source for exposure to these self-antigens. In genetically susceptible individuals, this could be one step in the series of events leading to autoimmunity.     

Methicillin-resistant Staphylococcus aureus in a teaching hospital: investigation of nosocomial transmission using a matched case-control study

In early 1996 a hospital-wide methicillin-resistant Staphylococcus aureus (MRSA) epidemic was recognized in a 900-bed university hospital. In order to investigate hospital-specific transmission routes, a case-control study was carried out. Cases and controls were matched for age (± 10 years), sex, admission date (± 10 days) and clinical department on admission. Data on potential risk factors, were retrieved by chart review. Between June 1996 and February 1997, 67 patients with hospital-acquired MRSA were identified. Molecular typing showed that 85% of the cases carried an indistinguishable strain. The average time at risk for cases and controls was 17.3 and 23.7 days, respectively (P= 0.01). Seventeen patients (25.4%) developed infection. Conditional multivariate regression analysis showed that intensity of care (P= 0.002), number of transfers (P= 0.019), and fluoroquinolone therapy (P= 0.025) were independently associated with acquisition of MRSA. Intensity of care can be considered as a surrogate marker for a number of manipulations which represent the main risk factors for MRSA transmission. Frequent transfers within the hospital hinder, not only the epidemiological analyses, but also efforts to bring an outbreak under control. Our findings give epidemiological support to recent molecular studies which suggest that fluoroquinolone use may increase the transmissibility of MRSA in hospitals.     

Epidemiological investigations of aircrew: an occupational group with low-level cosmic radiation exposure

Aircrew and passengers are exposed to low-level cosmic ionising radiation. Annual effective doses for flight crew have been estimated to be in the order of 2-5 mSv and can attain 75 mSv at career end. Epidemiological studies in this occupational group have been conducted over the last 15-20 years, usually with a focus on radiation-associated cancer. These studies are summarised in this note. Overall cancer risk was not elevated in most studies and subpopulations analysed, while malignant melanoma, other skin cancers and breast cancer in female aircrew have shown elevated incidence, with lesser risk elevations in terms of mortality. In some studies, including the large German cohort, brain cancer risk appears elevated. Cardiovascular mortality risks were generally very low. Dose information for pilots was usually derived from calculation procedures based on routine licence information, types of aircraft and routes/hours flown, but not on direct measurements. However, dose estimates have shown high validity when compared with measured values. No clear-cut dose-response patterns pointing to a higher risk for those with higher cumulative doses were found. Studies on other health outcomes have shown mixed results. Overall, aircrew are a highly selected group with many specific characteristics and exposures that might also influence cancers or other health outcomes. Radiation-associated health effects have not been clearly established in the studies available so far.