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.

     

A hazardous link between malnutrition, inflammation and oxidative stress in renal patients

BackgroundAtherosclerosis is the main cause of mortality in end stage renal disease (ESRD) patients.Design and methodsMalnutrition, inflammation and diminished paraoxonase activity were used to calculate the sum of risk factors for atherosclerosis development in a cohort of 141 chronic renal disease patients. Kaplan–Meier survival analysis was implemented to assess risk of death.ResultsKaplan–Meier analysis (Log rank = 12.06, P = 0.0072) showed higher risk of death with increasing number of risk factors in haemodialysis patients.ConclusionsMalnutrition in combination with inflammation and oxidative stress is associated with higher mortality in patients on long-term haemodialysis.     

Lysyl oxidase-like protein 2 (LOXL2) modulates barrier function in cholangiocytes in cholestasis

1. Download high-res image (278KB)
2. Download full-size image

     

The Emergence of SARS-CoV-2 within the Dog Population in Croatia: Host Factors and Clinical Outcome

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog populations. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralising antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Due to the retrospective nature of this study, samples for viral isolation and PCR were unavailable. Still, seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.     

Successful treatment of hepatitis C virus infection with direct‐acting antivirals during hematopoietic cell transplant

Current guidelines recommend that hepatitis C virus (HCV) infection be treated completely prior to hematopoietic cell transplantation or delayed until immune reconstitution after transplantation to avoid drug‐drug interactions and treatment interruption. However, these recommendations were informed by outcomes using treatment with ribavirin and pegylated interferon. We report the first case of successful treatment of HCV using direct‐acting antivirals during hematopoietic cell transplantation. This case study suggests that treatment of HCV concurrent with hematopoietic cell transplantation for malignancy may be the best option for some patients in whom it is unsafe to delay treatment for either disease.     

Protective effect of interferon-α on the DNA- and RNA-degrading pathway in anti-Fas-antibody induced apoptosis

Aim: Fas membrane-associated polypeptide antigen is a receptor molecule responsible for apoptosis-mediated signals. In animal models of acute viral hepatitis, apoptosis of hepatocytes is mediated by Fas-death receptors; therefore, the aim of this study was to evaluate the effect of interferon (IFN)-alpha on apoptotic markers and nuclease activity against different coding and non-coding single and double stranded RNAs during Fas-induced liver apoptosis. Methods: An in vivo experiment was performed with simultaneous administration of anti-Fas (CD95) antibodies and IFN-alpha, and an in vitro experiment was performed in hepatocyte cultures treated with anti-Fas antibodies and IFN-alpha. Results: Detection of apoptosis using Annexin V-FITC/propidium iodide, Bcl-2 and Bax expression in hepatocyte cultures confirmed the appearance of early apoptotic events and progression toward late apoptosis after anti-Fas antibody treatment. IFN-alpha had a tendency to retard the apoptosis process in Fas-induced apoptosis by increasing the number of viable cells and decreasing the number of cells in late apoptosis, by increasing the percentage of Bcl-2 positive cells, by decreasing the percentage of Bax positive cells, and by decreasing the nuclease activity compared to the anti-Fas antibody treated group. Total DNA and RNA concentration was much reduced in the Fas group and DNA fragmentation assay provided evidence for increased DNA degradation. Enhanced nuclease activity against DNA, rRNA, poly(A), poly(C), poly(U), poly(I:C), and poly(A:U) was manifested in the anti-Fas antibody treated group, except for the inhibitory-bound alkaline RNase. Conclusions: The results demonstrate that the RNA-degrading pathway in Fas-induced apoptosis can accelerate the liberation of the latent enzyme from the inhibitor complex. IFN-alpha prevented enormous, Fas-ligand induced degradation of all the substrates used in this experimental study, most probably due to similarities in the signal transduction pathways. Investigations of death receptor-induced apoptosis may lead to novel treatment combinations for patients with acute or chronic liver diseases.     

Construction and characterization of Listeria monocytogenes mutants with in-frame deletions in the response regulator genes identified in the genome sequence

Two-component systems are widely distributed in prokaryotes where they control gene expression in response to diverse stimuli. To study the role of the sixteen putative two-component systems of Listeria monocytogenes systematically, in frame deletions were introduced into 15 out of the 16 response regulator genes and the resulting mutants were characterized. With one exception the deletion of the individual response regulator genes has only minor effects on in vitro and in vivo growth of the bacteria. The mutant carrying a deletion in the ortholog of the Bacillus subtilis response regulator gene degU showed a clearly reduced virulence in mice, indicating that DegU is involved in the regulation of virulence-associated genes.     

First molecular evidence of Tula hantavirus in Microtus voles in Slovenia

Different Microtus species, present in a worldwide range habitat populating North America, Europe, Asia, and few other species have been recognized previously as a hantavirus reservoir. Tula hantavirus was first reported in Microtus arvalis and Microtus rossiaemeridionalis from Central Russia and later discovered in several European countries. Using molecular techniques we have demonstrated the presence of Tula hantavirus in three different Microtus species in Slovenia. Phylogenetic analyses of partial S segment placed Slovenian strains in the same genetic lineage as Austrian and Croatian strains.     

Eleven consecutive years of respiratory syncytial virus outbreaks in Croatia

Background:  Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infections (LRTI) in infants. The aim of the present study was to analyze the epidemiologic characteristics of RSV outbreaks in Croatian children.
Methods:  Over a period of 11 consecutive years (1994–2005), 3435 inpatients with acute respiratory infections (ARI) aged from birth to 10 years and were residing in Zagreb County were tested for infection with RSV and other respiratory viruses at the Virology Department, Croatian National Institute of Public Health. RSV was identified in nasopharyngeal secretions by isolation on cell culture and/or detection with monoclonal antibodies using a direct fluorescence assay.
Results:  RSV was the most common causative agent of ARI (42.2%; 658/1559) for the infants 0–6 months of age. It was also the etiologic agent of LRTI in 49% (495/1010) of infants of similar age. RSV was demonstrated in 56.5% (382/676) of infants with bronchiolitis, and in 36.5% (49/134) of those with pneumonia in this age group.
Conclusion:  The overall prevalence of RSV infection in Croatian children with acute respiratory illness, and its occurrence in various age groups, has remained stable over the past decade. RSV was found to be the most common cause of bronchiolitis occurring throughout childhood (52.7%; 482/913).     

Clinical and molecular genetic findings in a 6-year-old Bosnian boy with triple A syndrome

The triple A syndrome is a rare autosomal recessive disease that is characterised by the triad of adrenocorticotropin (ACTH)-resistant adrenal insufficiency, achalasia and alacrima. In most patients, neurological and dermatological abnormalities are associated features. We report on the first Bosnian patient with triple A syndrome. Endocrine investigation confirmed primary adrenal insufficiency at the age of 5.8 years. Two months lather, achalasia was diagnosed, and in the presence of alacrima, the patient satisfies the diagnostic criteria of triple A syndrome. In addition, a large number of associated neurological and dermatological features were present in this patient. Moreover, he has dysmorphic facial features, which have not been previously described in triple A syndrome. Triple A syndrome was confirmed by molecular analysis, revealing a nonsense mutation p.W84X in the AAAS gene. The parents are both heterozygous carriers of the mutation. The affected twin brother unfortunately died from hypoglycaemic shock, despite a normal cortisol rise in an ACTH stimulation test. Further, triple A syndrome patients carrying the identical homozygous p.W84X mutation have to be studied to assess a genotype–phenotype relationship for this mutation. Publication of these pictures was granted by the parents of the patient.