The Master of Puppets: Pleiotropy of PDGFRB and its Relationship to Multiple Diseases.

The platelet-derived growth factor receptor beta (PDGFRB) gene is involved in proliferative and developmental processes in mammals. Variations in this gene lead to several different syndromic conditions, such as infantile myofibromatosis I, sporadic port-wine stain, primary familial brain calcification, and the Penttinen and overgrowth syndromes. Our objective was to investigate PDGFRB's genetic relationship to clinical conditions and evaluate the protein interactions using GeneNetwork, GeneMANIA, and STRING network databases. We have evidenced the gene's pleiotropy through its many connections and its link to syndromic conditions. Therefore, PDGFRB may be an important therapeutic target for treating such conditions.

New Data from Pdfgb ret/ret Mutant Mice Might Lead to a Paradoxical Association Between Brain Calcification, Pericytes Recruitment and BBB Integrity.

Data of mice with PDGF-B-truncating mutation (Pdgfb ret/ret) from different research groups indicate that the malfunction of this protein leads to reduced pericyte recruitment, loss of Blood-Brain Barrier (BBB) integrity and bilateral brain calcification. This makes these mice important models for Primary Brain Calcification and pericyte-BBB correlation studies. The global brain pericyte count is reduced in Pdgfb ret/ret mice, with higher BBB permeability. We have overlapped the data from other research groups into a figure to further analyze the findings. Calcifications form within midbrain, interbrain, basal forebrain, and pons. Interestingly, these calcification-prone regions have a comparably higher pericyte count and lower BBB leakage in relation to other non-calcifying regions of the Pdgfb ret/ret mouse (such as the cortex and striatum). A comparatively higher BBB integrity in regions prone to calcification seems paradoxical and indicates that other region-specific changes are the cause of the calcifications.

Brain calcifications and PCDH12 variants.

OBJECTIVE: To assess the potential connection between PCDH12 and brain calcifications in a patient carrying a homozygous nonsense variant in PCDH12 and in adult patients with brain calcifications. METHODS: We performed a CT scan in 1 child with a homozygous PCDH12 nonsense variant. We screened DNA samples from 53 patients with primary familial brain calcification (PFBC) and 26 patients with brain calcification of unknown cause (BCUC). RESULTS: We identified brain calcifications in subcortical and perithalamic regions in the patient with a homozygous PCDH12 nonsense variant. The calcification pattern was different from what has been observed in PFBC and more similar to what is described in in utero infections. In patients with PFBC or BCUC, we found no protein-truncating variant and 3 rare (minor allele frequency <0.001) PCDH12 predicted damaging missense heterozygous variants in 3 unrelated patients, albeit with no segregation data available. CONCLUSIONS: Brain calcifications should be added to the phenotypic spectrum associated with PCDH12 biallelic loss of function, in the context of severe cerebral developmental abnormalities. A putative role for PCDH12 variants remains to be determined in PFBC.

Hand hygiene compliance in the critical care setting: a comparative study of 2 different alcohol handrub formulations.

BACKGROUND: Hand hygiene (HH) compliance can be affected by the accessibility of products (alcohol-based products or chlorhexidine) and by the formulations of these products. There are few published studies comparing different alcohol-based hand disinfection formulations. METHODS: This study was conducted in a 41-bed medical-surgical intensive care unit at a private tertiary care hospital. Over a 16-week period, we assessed HH compliance by direct observation of practice using iPods and measurement of the amount of product used [alcohol and chlorhexidine] in two 4-room pods in which an alcohol gel product was used compared with two other 4-room pods in which an alcohol-based foam formulation was used. RESULTS: A total of 3,895 opportunities for HH were observed, and the overall rate of HH compliance was 36.9%. No statistically significant differences were found in overall HH compliance or alcohol-based HH compliance between the alcohol foam unit and the alcohol gel unit. However, there was a statistically significant difference in chlorhexidine HH compliance between the alcohol foam unit and the alcohol gel unit (7.0% [130 of 1,853] vs 3.8% [77 of 2,042]; P < .01). CONCLUSIONS: Alcohol handrub use was greater than chlorhexidine use, but HH compliance was low in both units independent of the alcohol formulation available. The similarity of use of both alcohol formulations suggests that health care workers tend to use whatever product is readily available.

Preventing catheter-associated urinary tract infection in the zero-tolerance era.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is one of the most common health care‒associated infections in the critical care setting. METHODS: A quasi-experimental study involving multiple interventions to reduce the incidence of CAUTI was conducted in a medical-surgical intensive care unit (ICU) and in 2 step-down units (SDUs). Between June 2005 and December 2007 (phase 1), we implemented some Centers for Disease Control and Prevention‒recommended evidence-based practices. Between January 2008 and July 2010 (phase 2), we intervened to improve compliance with these practices at the same time that performance monitoring was being done at the bedside, and we implemented the Institute for Healthcare Improvement's bladder bundle for all ICU and SDU patients requiring urinary catheters. RESULTS: There was a statistically significant reduction in the rate of CAUTI in the ICU, from 7.6 per 1,000 catheter-days (95% confidence interval [CI], 6.6-8.6) before the intervention to 5.0 per 1,000 catheter-days (95% CI, 4.2-5.8; P < .001) after the intervention. There also was a statistically significant reduction in the rate of CAUTI in the SDUs, from 15.3 per 1,000 catheter-days (95% CI, 13.9-16.6) before the intervention to 12.9 per 1,000 catheter-days (95% CI, 11.6-14.2) after the intervention (P = .014). CONCLUSION: Our findings suggest that reducing CAUTI rates in the ICU setting is a complex process that involves multiple performance measures and interventions that can be applied to SDU settings as well.

Measuring rates of hand hygiene adherence in the intensive care setting: a comparative study of direct observation, product usage, and electronic counting devices.

OBJECTIVE: To compare 3 measures of hand hygiene adherence-direct observation, product usage, and electronic counting devices-in an intensive care unit. DESIGN: A 12-week observational study. SETTING: A 40-bed medical-surgical intensive care unit at a private tertiary care hospital. METHODS. Over a 12-week period, we assessed hand hygiene adherence by 3 different methods: direct observation of practice, collection of data from electronic counters for dispensers of alcohol-based hand rub, and measurement of the amount of product used (alcohol-based hand rub and chlorhexidine). RESULTS: There were 2,249 opportunities for hand hygiene observed, and the overall rate of hand hygiene adherence was 62.3% (representing 1,402 cleansing episodes). A total of 76,389 dispensing episodes were recorded by the electronic devices. The mean number of dispensing episodes per patient-day was 53.8. There was 64.1 mL of alcohol-based hand rub used per patient-day (representing 65.5% of total product used) and 33.8 mL of chlorhexidine used per patient-day (representing 34.5%). There was no significant correlation between observed hand hygiene adherence and total product used per patient-day (r=0.18; P=.59). CONCLUSIONS: Direct observation cannot be considered the gold standard for assessing hand hygiene, because there was no relationship between the observed adherence and the number of dispensing episodes or the volume of product used. Other means to monitor hand hygiene adherence, such as electronic devices and measurement of product usage, should be considered.

Impact of a program to prevent central line-associated bloodstream infection in the zero tolerance era.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) is one of the most important health care-associated infections in the critical care setting. METHODS: A quasiexperimental study involving multiple interventions to reduce the incidence of CLABSI was conducted in a medical-surgical intensive care unit (ICU) and in 2 step-down units (SDUs). From March 2005 to March 2007 (phase 1 [P1]), some Centers for Disease Control and Prevention evidence-based practices were implemented. From April 2007 to April 2009 (P2), we intervened in these processes at the same time that performance monitoring was occurring at the bedside, and we implemented the Institute for Healthcare Improvement central line bundle for all ICU and SDU patients requiring central venous lines. RESULTS: The mean incidence density of CLABSI per 1000 catheter-days in the ICU was 6.4 in phase 1 and 3.2 in phase 2, P < .001. The mean incidence density of CLABSI per 1000 catheter-days in the SDUs was 4.1 in phase 1 and 1.6 in phase 2, P = .005. CONCLUSION: These results suggest that reducing CLABSI rates in an ICU setting is a complex process that involves multiple performance measures and interventions that can also be applied to SDU settings.

Successful prevention of ventilator-associated pneumonia in an intensive care setting.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common health care-associated infections (HAIs) in critical care settings. OBJECTIVE: Our objective was to examine the effect of a series of interventions, implemented in 3 different periods to reduce the incidence of VAP in an intensive care unit (ICU). METHODS: A quasiexperimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize VAP prevention were performed during different phases. From March 2001 to December 2002 (phase 1: P1), some Centers for Disease Control and Prevention (CDC) evidence-based practices were implemented. From January 2003 to December 2006 (P2), we intervened in these processes at the same time that performance monitoring was occurring at the bedside, and, from January 2007 to September 2008 (P3), we continued P2 interventions and implemented the Institute for Healthcare Improvement's ventilator bundle plus oral decontamination with chlorhexidine and continuous aspiration of subglottic secretions. RESULTS: The incidence density of VAP in the ICU per 1000 patient-days was 16.4 in phase 1, 15.0 in phase 2, and 10.4 in phase 3, P=.05. Getting to zero VAP was possible only in P3 when compliance with all interventions exceeded 95%. CONCLUSION: These results suggest that reducing VAP rates to zero is a complex process that involves multiple performance measures and interventions.