A continuous quality-improvement program reduces nosocomial infection rates in the ICU

Objective To assess the impact of a continuous quality-improvement program on nosocomial infection rates.Design and setting Prospective single-center study in the medical-surgical ICU of a tertiary care center.Patients We admitted 1764 patients during the 5-year study period (1995–2000); 55% were mechanically ventilated and 21% died. Mean SAPS II was 37±21 points and mean length of ICU stay was 9.7±16.1 days.Interventions Implementation of an infection control program based on international recommendations. The program was updated regularly according to infection and colonization rates and reports in the literature.Measurements and results Prospective surveillance showed the following rates per 1000 procedure days: ventilator-associated pneumonia (VAP) 8.7, urinary tract infection (UTI) 17.2, central venous catheter (CVC) colonization 6.1, and CVC-related bacteremia and2.0; arterial catheter colonization did not occur. In the 5 years following implementation of the infection control program there was a significant decline in the rate per patient days of UTI, CVC colonization, and CVC-related bacteremia but not VAP. Between the first and second 2.5-year periods the time to infection increased significantly for UTI and CVC-related colonization.Conclusions A continuous quality-improvement program based on surveillance of nosocomial infections in a nonselected medical-surgical ICU population was associated with sustained decreases in UTI and CVC-related infections.Electronic Supplementary Material Supplementary material is available in the online version of this article at .     

Allelic estrogen receptor 1 (ESR1) gene variants predict the outcome of ovarian stimulation in in vitro fertilization

The outcome of in vitro fertilization (IVF) depends substantially on the effectiveness of controlled ovarian hyperstimulation (COH) induced by administration of follicle-stimulating hormone (FSH). In COH, endogenously produced estrogens extend the action of FSH in stimulating folliculogenesis. We determined the associations between genetic variations in estrogen receptor ESR1 and ESR2 genes and etiology of female infertility, and analysed the influence of these variations on COH outcome-the quantity and quality of oocytes retrieved. ESR1 PvuII T/C (rs2234693) and XbaI A/G (rs9340799) single-nucleotide polymorphisms (SNPs) and (TA)n microsatellite polymorphism, as well as ESR2 RsaI G/A (rs1256049) SNP and (CA)n microsatellite polymorphism were genotyped in 159 IVF patients. The ovarian response to FSH was diminished in patients with endometriosis when compared to tubal factor infertility. ESR1 PvuII and XbaI as well as ESR2 RsaI SNPs were associated with the microsatellite length of the respective genes. Shorter ESR1 (TA)n was linked with a higher risk for unexplained infertility, whereas longer ESR1 (TA)n associated with PvuII*C allele were predictive of a better COH, but not clinical pregnancy outcome in an age-independent manner. These data suggest the variations in ESR1 gene, in addition to the age of a woman, may predict the COH outcome in IVF.     

Ability of family members to predict patient's consent to critical care research

Objective

A European Union Directive provides for the designation of a surrogate who can consent to or refuse inclusion of an incapacitated patient in research studies. The accuracy with which surrogates consent to research on behalf of patients has not been evaluated in the intensive care unit (ICU).

Methods

A prospective multicenter study was conducted in ten ICUs of the French Famirea study group between July and October 2004. Two hypothetical studies were simultaneously submitted to the patient, surrogate, and physician at the time that the patient was discharged to a ward. One study involved minimal risk and the other greater-than-minimal risk to the patients.

Results

With the minimal risk study there was patient-surrogate discrepancy in 32% of cases and patient-physician discrepancy in 25%. Corresponding figures with the greater-than-minimal risk study were 42% and 46%. None of the collected variables differed significantly between cases with and without patient-surrogate discrepancy.

Conclusions

Family members designated to serve as surrogate decision makers may fail to accurately consent to research for critically ill patients in one-third to nearly one-half of cases.     

Body mass index

Objective To examine the association between body mass index (BMI) and mortality in adult intensive care unit (ICU) patients.Design A prospective multi-center study.Interventions None.Methods A cohort study (yielding the OUTCOMEREA database) was conducted over 2 years in 6 medical-surgical ICUs. In each participating ICU, the following were collected daily: demographic information, admission height and weight, comorbidities, severity scores (SAPS II, LOD, and SOFA), ICU and hospital lengths of stay, and ICU and hospital mortality rates.Results A total of 1,698 patients were examined and divided into 4 groups based on BMI: <18.5, 18.5–24.9, 25–29.9, and >30 kg/m². These groups differed significantly for age, gender, admission category (medical, scheduled surgery, unscheduled surgery), ICU and hospital lengths of stay, and comorbidities. Severity at admission and within the first 2 days was similar in the 4 groups, except for the SOFA score. Overall hospital mortality was 31.3% (532 out of 1,698 patients). By multivariate analysis, a BMI below 18.5 kg/m² was independently associated with increased mortality (odds ratio 1.63; 95% confidence intervals 1.11–2.39). None of the other BMI categories were associated with higher mortality and even a BMI>30 kg/m² was protective of mortality (odds ratio 0.60, 95% confidence intervals 0.40–0.88).Conclusions A low BMI was independently associated with higher mortality and a high BMI with lower mortality in this large cohort of critically ill patients. Since BMI is absent from currently available scoring systems, further studies are needed to determine whether adding BMI would improve the effectiveness of scores in predicting mortality.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-003-2095-2.The members of the OUTCOMEREA study group are listed in the appendix.Financial support: OUTCOMEREA is supported by non-exclusive educational grants from Aventis Pharma, France, Wyeth, and the Centre National de la Recherche Scientifique (CNRS).     

BRCA1 mutations in women with familial or early-onset breast cancer and BRCA2 mutations in familial cancer in Estonia

Background

The aim of this study was to identify BRCA1 and BRCA2 mutations in the Estonian population. We analyzed genetic data and questionnaire from 64 early-onset (< 45 y) breast cancer patients, 47 familial cases (patients with breast or ovarian cancer and a case of these cancers in the family), and 33 predictive cases (patients without breast or ovarian cancer, with a family history of such diseases) from Estonia for mutations in the BRCA1 gene. A sub-set of familial cases and predictive cases were also analyzed for mutations in the BRCA2 gene.

Methods

For mutation detection, we used the Polymerase Chain Reaction-Single Stranded Conformation Polymorphism Heteroduplex Analysis (PCR-SSCP-HD), followed by direct DNA sequencing.

Results

We identified three clinically important mutations in the BRCA1 gene, including seven occurrences of the c.5382insC mutation, three of c.4154delA, and one instance of c.3881_3882delGA. We also detected six polymorphisms: c.2430T>C, c.3232A>G, c.4158A>G, c.4427T>C, c.4956A>G, and c.5002T>C. Four sequence alterations were detected in introns: c.560+64delT, c.560+ [36-38delCTT, 52-63del12], c.666-58delT, and c.5396+60insGTATTCCACTCC. In the BRCA2 gene, two clinically important mutations were found: c.9610C>T and c.6631delTTAAATG. Additionally, two alterations (c.7049G>T and c.7069+80delTTAG) with unknown clinical significance were detected.

Conclusions

In our dataset, the overall frequency of clinically important BRCA1 mutations in early-onset patients, familial cases, and predictive testing was 7.6% (144 cases, 11 mutation carriers). Pathogenic mutations were identified in 4 of the 64 early-onset breast cancer cases (6.3%). In familial cases, clinically important mutations in the BRCA1 gene were found in 6 of the 47 individuals analyzed (12.8%). In predictive cases, 1 clinically important mutation was detected in 33 individuals studied (3%). The occurrence of clinically important mutations in BRCA2 in familial cases of breast cancer was 2 of the 16 individuals analyzed (12.5%).     

Blocking of Striated Muscle Degeneration by Serotonin in C. elegans

Prevention of muscle fiber degeneration is a key issue in the treatment of muscular dystrophies such as Duchenne Muscular Dystrophy (DMD). It is widely postulated that existing pharmaceutical compounds might potentially be beneficial to DMD patients, but tools to identify them are lacking. Here, by using a Caenorhabditis elegans model of dystrophin-dependent muscular dystrophy, we show that the neurohormone serotonin and some of its agonists are potent suppressors of muscle degeneration. Inhibitors of serotonin reuptake transporters, which prolong the action of endogenous serotonin, have a similar effect. Moreover, reduction of serotonin levels leads to degeneration of non-dystrophic muscles. Our results demonstrate that serotonin is critical to C. elegans striated muscles. These findings reveal a new fonction of serotonin in striated muscles.