Previous healthcare exposure is the main antecedent for methicillin-resistant Staphylococcus aureus carriage on hospital admission in Belgium

This study aimed to estimate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage upon hospital admission and to study the molecular epidemiology of MRSA in order to assess the proportion of Panton-Valentine leukocidin (PVL)-positive community-associated (CA) and livestock-associated (LA) MRSA strains. Epidemiological data on MRSA carriage upon hospital admission (2006-2009) were collected in a compulsory, continuous, national MRSA surveillance in Belgian acute-care hospitals. Additionally, 328 MRSA strains in 2005 and 314 strains in 2008 were collected in a separate, multicenter microbiological survey. Spa-typing, SCCmec-typing and MLST were performed; toxin genes were detected by PCR. The overall prevalence of MRSA carriage upon hospital admission was 8.9 cases/1,000 admissions between 2006 and 2009. Of MRSA carriers, 37.5% had a known MRSA history, 39.4% had stayed in a care facility, 12.2% reported no contact with healthcare. Over 90% of MRSA belonged to five healthcare-associated clones. Of these, MRSA spa-CC038-ST45-IV was in decline, mainly in favor of spa-CC008-ST8-IV. MRSA spa-CC002-ST5-IV, spa-CC002-ST5-II and spa-CC032-ST22-IV remained relatively stable. The proportion of PVL-positive CA-MRSA and LA-MRSA ST398 was below 2% of all MRSA. The extra-hospital MRSA reservoir in Belgium mainly consists of persons with previous healthcare exposure. PVL-positive CA-MRSA and LA-MRSA strains remained infrequent among hospitalized patients.     

A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency

Microsatellite instability (MSI) occurs in 10–20% of colorectal tumours and is associated with good prognosis. Here we describe the development and validation of a genomic signature that identifies colorectal cancer patients with MSI caused by DNA mismatch repair deficiency with high accuracy. Microsatellite status for 276 stage II and III colorectal tumours has been determined. Full‐genome expression data was used to identify genes that correlate with MSI status. A subset of these samples (n = 73) had sequencing data for 615 genes available. An MSI gene signature of 64 genes was developed and validated in two independent validation sets: the first consisting of frozen samples from 132 stage II patients; and the second consisting of FFPE samples from the PETACC‐3 trial (n = 625). The 64‐gene MSI signature identified MSI patients in the first validation set with a sensitivity of 90.3% and an overall accuracy of 84.8%, with an AUC of 0.942 (95% CI, 0.888–0.975). In the second validation, the signature also showed excellent performance, with a sensitivity 94.3% and an overall accuracy of 90.6%, with an AUC of 0.965 (95% CI, 0.943–0.988). Besides correct identification of MSI patients, the gene signature identified a group of MSI‐like patients that were MSS by standard assessment but MSI by signature assessment. The MSI‐signature could be linked to a deficient MMR phenotype, as both MSI and MSI‐like patients showed a high mutation frequency (8.2% and 6.4% of 615 genes assayed, respectively) as compared to patients classified as MSS (1.6% mutation frequency). The MSI signature showed prognostic power in stage II patients (n = 215) with a hazard ratio of 0.252 (p = 0.0145). Patients with an MSI‐like phenotype had also an improved survival when compared to MSS patients. The MSI signature was translated to a diagnostic microarray and technically and clinically validated in FFPE and frozen samples. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Use of free-standing filters in an asthma intervention study

This study characterizes the use of HEPA air filters provided to 89 households participating in an intervention study investigating the respiratory health of children with asthma. Free-standing filters were placed in the child's bedroom and monitored continuously for nearly a year in each household. Filter use was significantly affected by study phase, season, and monitoring week. During the “intensive” weeks when a community education worker and a field technician visited the household, the use rate averaged 70?±?33 %. During season-long “non-intensive” periods between seasonal visits, use dropped to 34?±?30 %. Filter use rapidly decreased during the 3 to 4 weeks following each intensive, and was slightly higher in spring, summer, and in the evening and at night when the child was likely to be home, although households did not follow consistent diurnal patterns. While participants expressed an understanding of the benefits of filter use and reported good experiences with them, use rates were low, particularly during unobserved non-intensive periods. The provision of free-standing air filters to individuals or households must be considered an active intervention that requires monitoring and evaluation; otherwise, unknown and unexpected patterns of filter use may alter and possibly bias results due to exposure misclassification.     

Associations of 25-hydroxyvitamin D with fasting glucose, fasting insulin, dementia and depression in European elderly: the SENECA study

Purpose

The classical consequence of vitamin D deficiency is osteomalacia, but recent insights into the function of vitamin D suggest that it may play a role in other body systems as well. The objective of this study was to examine the association between 25-hydroxyvitamin D (25(OH)D) and markers of glucose metabolism (n = 593), global cognitive functioning (n = 116) and depression (n = 118) in European elderly participating in the SENECA study. Moreover, we wanted to explore whether the observed associations of 25(OH)D with depression and global cognitive performance were mediated by fasting plasma glucose (FPG) levels.

Methods

Cross-sectional associations between 25(OH)D and FPG, fasting plasma insulin (FPI) and homeostatic model assessment-insulin resistance (HOMA-IR), a marker of insulin resistance, were estimated from multiple regression analyses. Associations of 25(OH)D with global cognitive functioning (Mini Mental State Examination) and depression (Geriatric Depression Scale) were examined using Poisson regression.

Results

An inverse association was observed between 25(OH)D and FPG (β-0.001), indicating a 1 % decrease in FPG per 10 nmol/L increase in 25(OH)D, but after full adjustment for demographic factors, lifestyle factors and calcium intake, this association was not statistically significant (P = 0.07). Although participants with intermediate and high serum 25(OH)D levels showed a tendency towards a lower depression score after adjustment for demographic and lifestyle factors, RR and 95 % CI: 0.73 (0.51–1.04) and 0.76 (0.52–1.11), respectively, these findings were not statistically significant.

Conclusion

An inverse association of 25(OH)D with depression and FPG was observed, but this association was not statistically significant. There was no association between 25(OH)D with FPI and HOMA-IR or with global cognitive functioning. More studies are needed to further explore the possible role of vitamin D in the various body systems.     

Exploring Multitarget Interactions to Reduce Opiate Withdrawal Syndrome and Psychiatric Comorbidity

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Immunodysregulation of HIV disease at bone marrow level

Hematological abnormalities frequently occur in patients infected with HIV-1. Increasing evidence indicates that bone marrow (BM) suppression results from viral infection of accessory cells, with impaired stromal function and alteration of hematopoietic growth factor network. We investigated the effects of antiretroviral therapy on cytokine and chemokine production by BM cells and stromal cells, in a group of HIV-1-infected subjects before and during treatment. Compared with uninfected controls, an altered cytokine and chemokine production by BM cells has been observed before treatment, characterised by decreased IL-2 and elevated TNF-alpha, MIP-1alpha, MIP-1beta, and RANTES levels, along with a defective BM clonogenic activity. Antiretroviral therapy determined an amelioration of stem cell activity, a restoration of stromal cell pattern and functions, and an increased IL-2 production at BM level and a decrease of Fas expression on progenitor cells, in parallel with the diminution of TNF-alpha levels. HIV-1 protease inhibitors (PIs) may improve hematopoietic functions owing to their direct effects on the BM progenitor cells. Ritonavir and indinavir increased the colony growth of BM obtained either from HIV-1-infected patients or from normal individuals, in parallel with the normalization of functional and morphologic characteristics of stromal cells.     

Growth hormone therapy and hypersensitivity type III reaction: a contraindication for desensitization

Allergic reactions against GH are rare, and usually represented by the hypersensitivity type I (IgE-mediated). This type of reaction can be treated by desensitization. In this case report, we present a patient showing an allergic reaction soon after starting GH therapy mediated by immune complex (hypersensitivity type III reaction). In this condition, the attempt to perform the desensitization procedure can perpetuate immune complex deposition determining a life threatening renal and respiratory insufficiency.