Complement factor D is linked to platelet activation in human and rodent sepsis.

BACKGROUND: The complement factor D (CFD) exerts a regulatory role during infection. However, its physiological function in coagulopathy and its impact on the course of an infection remains unclear. MATERIALS: Wild-type and CFD-deficient mice (n = 91) were subjected to cecal ligation and puncture to induce sepsis. At several time points, markers of coagulation and the host-immune response were determined. Furthermore, in patients (n = 79) with sepsis or SIRS, CFD levels were related to clinical characteristics, use of antiplatelet drugs and outcome. RESULTS: Septic CFD-deficient mice displayed higher TAT complexes (p = 0.02), impaired maximal clot firmness, but no relevant platelet drop and reduced GPIIb/IIIa surface expression on platelets (p = 0.03) compared to septic wild-type mice. In humans, higher CFD levels (non-survivors, 5.0 µg/ml to survivors, 3.6 µg/ml; p = 0.015) were associated with organ failure (SOFA score: r = 0.33; p = 0.003) and mortality (75% percentile, 61.1% to 25% percentile, 26.3%). CFD level was lower in patients with antiplatelet drugs (4.5-5.3 µg/ml) than in patients without. CONCLUSION: In mice, CFD is linked to pronounced platelet activation, depicted by higher GPIIb/IIIa surface expression in wild-type mice. This might be of clinical importance since high CFD plasma concentrations were also associated with increased mortality in sepsis patients.

Health related quality of life associated with extreme obesity in adolescents - results from the baseline evaluation of the YES-study.

BACKGROUND: Obesity can significantly reduce health-related quality of life (HRQoL) and may lead to numerous health problems even in youths. This study aimed to investigate whether HRQoL varies among youths with obesity depending on grade of obesity and other factors. METHODS: For the Youths with Extreme obesity Study (YES) (2012-2014), a prospective multicenter cohort study, a baseline sample of 431 obese and extremely obese adolescents and young adults (age 14 to 24 years, BMI ≥30 kg/m2) was recruited at four German university medical centers and one job center. Obesity grade groups (OGG) were defined according to BMI (OGG I: 30-34.9 kg/m2, OGG II: 35-39.9 kg/m2, OGG III (extreme obesity): ≥40 kg/m2). HRQoL was measured with the Euroqol-5D-3 L (EQ-5D-3 L), DISABKIDS chronic generic (DCGM-31) and the KINDLR obesity module. Differences between OGGs were assessed with logistic and linear regression models, adjusting for age, sex, and study center in the base model. In a second regression analysis, we included other characteristics to identify possible determinants of HRQoL. RESULTS: Three hundred fifty-two adolescents (mean age: 16.6 (±2.4), mean BMI: 39.1 (±7.5) kg/ m2) with available HRQoL data were analysed. HRQoL of youths in all OGGs was markedly lower than reference values of non-obese adolescents. Adjusting for age and sex, HRQoL of youths in OGG III significantly impaired compared to OGG I. Youths in OGG III were 2.15 times more likely to report problems with mobility in the EQ-5D-3 L than youths in OGG I. A mean difference of 9.7 and 6.6 points between OGG III and I were found for DCGM-31 and KINDL respectively and 5.1 points between OGG II and I for DCGM-31. Including further variables into the regression models, showed that HRQoL measured by DCGM-31 was significantly different between OGGs. Otherwise, female sex and having more than 4 h of daily screen time were also associated with lower HRQoL measured by DCGM-31 and KINDL. CONCLUSION: HRQoL of adolescents with obesity is reduced, but HRQoL of adolescents with extreme obesity is particularly affected. Larger and longitudinal studies are necessary to understand the relation of extreme obesity and HRQoL, and the impact of other lifestyle or socioeconomic factors. TRIAL REGISTRATION: Clinicaltrials.gov NCT01625325; German Clinical Trials Register (DRKS) DRKS00004172.

Cefazolin versus anti-staphylococcal penicillins for the treatment of patients with Staphylococcus aureus bacteraemia.

BACKGROUND: For patients with bacteraemia caused by methicillin-sensitive Staphylococcus aureus anti-staphylococcal penicillins (ASPs) or cefazolin are agents of choice. While ASPs are potentially nephrotoxic, cefazolin may be less effective in some S. aureus strains due to an inoculum effect. OBJECTIVES: To perform a systematic literature review and meta-analysis assessing current evidence comparing cefazolin with ASPs for patients with S. aureus bacteraemia (SAB). METHODS: We searched MEDLINE, ISI Web of Science (Science Citation Index Expanded) and the Cochrane Database as well as clinicaltrials.gov from inception to 26 June 2018. All studies investigating the effects of cefazolin versus ASP in patients with methicillin-sensitive SAB were eligible for inclusion regardless of study design, publication status or language. Additional information was requested by direct author contact. A meta-analysis to estimate relative risks (RRs) with the corresponding 95% confidence intervals (CIs) was performed. Statistical heterogeneity was estimated using I2. The primary endpoint was 90-day all-cause mortality. The Newcastle-Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used for study and data quality assessment. RESULTS: Fourteen non-randomized studies were included. Seven reported the primary endpoint (RR 0.71 (0.50, 1.02), low quality of evidence). Cefazolin treatment may be associated with lower 30-day mortality rates (RR 0.70 (0.54, 0.91), low quality of evidence) and less nephrotoxicity (RR 0.36 (0.21, 0.59), (low quality of evidence)). We are uncertain whether cefazolin and ASP differ regarding treatment failure/relapse as the quality of the evidence has been assessed as very low (RR of 0.84 (0.59, 1.18)). For patients with endocarditis (RR 0.71 (0.12, 4.05)) or abscesses (RR 1.17 (0.30, 4.63)), cefazolin treatment may be associated with equal 30-day and 90-day mortality (low quality of evidence). CONCLUSIONS: Cefazolin seemed to be at least equally as effective as ASPs while being associated with less nephrotoxicity.

Effectiveness of a hospital-wide infection control programme on the incidence of healthcare-associated infections and associated severe sepsis and septic shock: a prospective interventional study.

OBJECTIVES: To evaluate whether a hospital-wide infection control programme (ICP) is effective at reducing the burden of healthcare-associated infections (HAIs) and associated severe sepsis/septic shock or death (severe HAIs). METHODS: Prospective, quasi-experimental study with two surveillance periods (September 2011 to August 2012; May 2013 to August 2014). Starting October 2012, the ICP included hand hygiene promotion and bundle implementation for common HAIs. We applied segmented mixed-effects Poisson regression and multi-state models. We reported adjusted incidence rate ratios (aIRR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). RESULTS: Overall, 62 154 patients were under surveillance, with 1568 HAIs identified in 1170 patients (4.3 per 100 admissions) in the first and 2336 HAIs identified in 1711 patients (4.9 per 100 admissions) in the second surveillance period. No differences were found in the overall HAI incidence rates between the periods in the general wards (aIRR 1.29, 95% CI 0.78-2.15) and intensive care units (ICUs) (aIRR 0.59, 95% CI 0.27-1.31). However, the HAI incidence rate was declining in the ICUs after starting the ICP (aIRR 0.98, 95% CI 0.97-1.00 per 1-week increment), in contrast to general wards (aIRR 1.01, 95% CI 1.00-1.02). A reduction in severe HAIs (aIRR 0.13, 95% CI 0.05-0.32) and a lower probability of HAI-associated in-hospital deaths (aHR 0.56, 95% CI 0.31-0.99) were observed in the second period in the ICUs. CONCLUSIONS: There was no overall reduction in HAIs after implementation of the ICP. However, there was a significant reduction in severe HAIs in ICUs. Whether this difference was a consequence of the ICP or improvement in HAI case management is not clear.

[Epistemology in the intensive care unit-what is the purpose of a definition? : Paradigm shift in sepsis research]. / Erkenntnistheorie auf der Intensivstation ­ Welchen Zweck erfüllt eine Definition? : Paradigmenwechsel in der Sepsisforschung.

The adoption of the new sepsis definition in early 2016 introduced a new paradigm for the clinical picture of sepsis. Up until now, sepsis was defined as a systemic inflammatory reaction (systemic inflammatory response syndrome, SIRS) to an infection. Based on a better understanding of the molecular mechanisms, the focus of the new definition is no longer the inflammatory response, but rather the tissue damage and impairment of organ function which this induces. The paradigm thus moves away from the infection and the systemic inflammatory response, and toward that which makes sepsis so dangerous in terms of both disease dynamics and outcome: organ failure due to a dysregulated host response to an infection. This change of perspective or paradigm enables patients with an increased risk of developing sepsis to be recognized and treated earlier in clinical routine, even outside of the intensive care unit. The new definition also promotes development of new treatment strategies with improved ability to treat sepsis causally.

Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.

INTRODUCTION: Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question. METHODS AND ANALYSIS: SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90 days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC. ETHICS AND DISSEMINATION: We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media. TRIAL REGISTRATION NUMBER: DRKS00010135.

Effect of pre-operative octenidine nasal ointment and showering on surgical site infections in patients undergoing cardiac surgery.

OBJECTIVE: To evaluate the effect of pre-operative octenidine (OCT) decolonization on surgical site infection (SSI) rates. DESIGN: Before-and-after cohort study. PATIENTS: Patients undergoing an elective isolated coronary artery bypass graft (CABG) procedure: control group (1st January to 31st December 2013), N=475; intervention group (1st January to 31st December 2014), N=428. INTERVENTIONS: The intervention consisted of nasal application of OCT ointment three times daily, beginning on the day before surgery, and showering the night before and on the day of surgery with OCT soap. RESULTS: A median sternotomy was performed in 805 (89.1%) patients and a minimally invasive direct coronary artery bypass procedure was performed in 98 (10.9%) patients. Overall, there was no difference in SSI rates between the control and intervention groups (15.4% vs 13.3%, P=0.39). The rate of harvest site SSIs was significantly lower in patients in the intervention group (2.5% vs 0.5%, P=0.01). Patients who had undergone a median sternotomy in the intervention group had a significantly lower rate of organ/space sternal SSIs (1.9% vs 0.3%, P=0.04). However, there was a trend towards an increased rate of deep incisional sternal SSIs (1.2% vs 2.9%, P=0.08). Multi-variate analysis did not identify a significant protective effect of the intervention (odds ratio 0.79, 95% confidence interval 0.53-1.15, P=0.27). CONCLUSIONS: Pre-operative decolonization with OCT did not reduce overall SSI rates in patients undergoing an elective isolated CABG procedure, but significantly decreased harvest site and organ/space sternal SSIs. Randomized controlled trials, including controlled patient adherence to the intervention, are required to confirm these observations and to determine the clinical utility of OCT in pre-operative decolonization.

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index.

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation.

Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.

Bipolar disorder risk alleles in children with ADHD.

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) may share common genetic risk factors as indicated by the high co-morbidity of BD and ADHD, their phenotypic overlap especially in pediatric populations, the high heritability of both disorders, and the co-occurrence in families. We therefore examined whether known polygenic BD risk alleles are associated with ADHD. We chose the eight best SNPs of the recent genome-wide association study (GWAS) of BD patients of German ancestry and the nine SNPs from international GWAS meeting a 'genome-wide significance' level of α = 5 × 10(-8). A GWAS was performed in 495 ADHD children and 1,300 population-based controls using HumanHap550v3 and Human660 W-Quadv1 BeadArrays. We found no significant association of childhood ADHD with single BD risk alleles surviving adjustment for multiple testing. Yet, risk alleles for BD and ADHD were directionally consistent at eight of nine loci with the strongest support for three SNPs in or near NCAN, BRE, and LMAN2L. The polygene analysis for the BP risk alleles at all 14 loci indicated a higher probability of being a BD risk allele carrier in the ADHD cases as compared to the controls. At a moderate power to detect association with ADHD, if true effects were close to estimates from GWAS for BD, our results suggest that the possible contribution of BD risk variants to childhood ADHD risk is considerably lower than for BD. Yet, our findings should encourage researchers to search for common genetic risk factors in BD and childhood ADHD in future studies.

Analyses of non-synonymous obesity risk alleles in SH2B1 (rs7498665) and APOB48R (rs180743) in obese children and adolescents undergoing a 1-year lifestyle intervention.

Association of obesity risk alleles of single nucleotide polymorphisms (SNPs) near or in the SH2B adaptor protein 1 gene (SH2B1) and increased body mass index (BMI) has been often described. A gene in close proximity, apolipoprotein B48 receptor gene (APOB48R), is tagged by the same SNP(s).We analyzed 454 overweight and obese children and adolescents (10.8±2.6 years, BMI-SDS 2.4±0.5; 55% girls) who completed a 1-year lifestyle intervention ('Obeldicks' program). Carriers of obesity risk alleles of non-synonymous SNPs in SH2B1 (rs7498665, Thr484Ala) or APOB48R (rs180743, Pro419Ala), as genotyped by TaqMan, were analysed for changes in anthropometrics (body-mass index (BMI), and standardized BMI (BMI-SDS)), blood pressure (systolic and diastolic) and plasma parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides, glucose, insulin, and HOMA).We observed no evidence for an association of the obesity risk alleles to alterations in any of the analyzed phenotypes. Both mean BMI and BMI-SDS improved during the intervention independent of genotype. The mean systolic blood pressure was lowered and concentrations of HDL-cholesterol increased significantly.The obesity risk alleles of non-synonymous SNPs at SH2B1 and APOB48R have no strong effect on weight loss-related phenotypes in overweight children after a 1-year lifestyle intervention.

The fatty acid amide hydrolase (FAAH) gene variant rs324420 AA/AC is not associated with weight loss in a 1-year lifestyle intervention for obese children and adolescents.

Adult obese carriers of the A allele of SNP rs324420 in the fatty acid amide hydrolase (FAAH) gene lose more weight and improve associated phenotypes better than non-carriers during an intervention. We aimed to replicate this finding in obese children and adolescents undergoing a one year lifestyle intervention (Obeldicks program). A total of 453 overweight and obese children and adolescents (10.8±2.6 years, BMI-SDS 2.4±0.5; 55% girls) were genotyped for rs324420 (C/A) by restriction fragment length polymorphism (RFLP) analysis. Participants were prescribed a balanced diet, containing 55 En% carbohydrates, 30 En% fat, and 15 En% proteins. Moreover, they took part in an exercise therapy once a week. Blood was taken at baseline and after 1 year of intervention. Anthropometric (height, weight, BMI, and BMI-SDS) and plasma parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides, glucose, insulin, and HOMA) as well as blood pressure were measured. Both mean BMI and BMI-SDS improved significantly. The mean systolic blood pressure was also lowered and concentrations of HDL-cholesterol increased significantly. However, none of the measured changes were associated with FAAH rs324420 AA/AC genotype. We did not detect evidence for an association of FAAH genotypes with weight reduction in overweight and obese children and adolescents. Hence, the previous finding in adults could not be confirmed. As the length (1 year as compared to 3 months) and mode of treatment (hypocaloric diet in adults vs. physical activity plus balanced meals) of the interventions varied, these parameters might have influenced the inconsistent results.

Randomized comparison of synchronous CABG and carotid endarterectomy vs. isolated CABG in patients with asymptomatic carotid stenosis: the CABACS trial.

RATIONALE: High-grade carotid artery stenosis is present in 6-8% of patients undergoing coronary artery bypass graft surgery. Many cardiovascular surgeons advocate staged or synchronous carotid endarterectomy to reduce the high perioperative and long-term risk of stroke associated with multivessel disease. However, no randomized trial has assessed whether a combined synchronous or staged carotid endarterectomy confers any benefit compared with isolated coronary artery bypass grafting in these patients. AIMS: The objective of this study is to compare the safety and efficacy of isolated coronary artery bypass grafting vs. synchronous coronary artery bypass grafting and carotid endarterectomy in patients with asymptomatic high-grade carotid artery stenosis. DESIGN: Coronary Artery Bypass graft surgery in patients with Asymptomatic Carotid Stenosis (CABACS) is a randomized, controlled, open, multicenter, group sequential trial with two parallel arms and outcome adjudication by blinded observers. Patients with asymptomatic high-grade carotid stenosis scheduled for elective coronary artery bypass grafting will be assigned to either isolated coronary artery bypass grafting or synchronous coronary artery bypass grafting and carotid endarterectomy by 1 : 1 block-stratified randomization with three different stratification factors (age, gender, modified Rankin scale). STUDY: The trial started in December 2010 aiming at recruiting 1160 patients in 25 to 30 German cardiovascular centers. The composite primary efficacy end point is the number of strokes and deaths from any cause (whatever occurs first) within 30 days after operation. A 4·5% absolute difference (4% compared to 8·5%) in the 30-day rate of the above end points can be detected with >80% power. OUTCOMES: The results of this trial are expected to provide a basis for defining an evidence-based standard and will have a wide impact on managing this disease.

[Genotype of the GNB3 C825T polymorphism, A risk factor for the development and course of prostate cancer?]. / Genotyp des GNB3-C825T-Polymorphismus. Risikofaktor für die Entwicklung und den Verlauf eines Prostatakarzinoms?

BACKGROUND: G protein-mediated signal transduction plays a key role in pathways of metastasis. A C/T polymorphism (dbSNP rs5443) at position 825 of the GNB3 gene has been described. Previous studies demonstrated an association between the GNB3 C825T genotype and different cancer entities. PATIENTS AND METHODS: In this report genotyping for this marker was performed in 235 prostate cancer patients and 111 healthy control subjects. Clinical follow-up data were available for a subset of 197 patients. RESULTS: Neither significant evidence for differences in genotype distributions between the prostate cancer cases and controls (odds ratio CT/TT=0.94, 95% CI 0.58-1.51, p=.82) nor evidence for genotype differences in e.g. progression-free survival in the subset of patients was observable (hazard ratio CT/TT=0.77, 95% CI 0.44-1.37, p=.38). Similar results were obtained in the subgroup of patients with primary tumor stage ≤ pT2 N0 M0 undergoing radical prostatectomy. CONCLUSION: Our data do not support an association between prostate cancer and the genotype of the GNB3 C825T polymorphism. This finding might either indicate a much smaller genetic effect undetectable with the given sample size or a possible hormone dependence of the disease superimposed on the potential effect of the GNB3 C825T genotype.

Lack of association of the genotype in the GNAS Fok I polymorphism and prostate cancer.

BACKGROUND: G proteins are ubiquitously expressed signal transduction proteins playing a key role in multiple signal transduction pathways. The Gαs subunit has been considered as an apoptosis factor. In this study the role of GNAS T393C genotypes of the GNAS gene encoding Gαs was analyzed for its influence on the development and progression of prostate cancer. METHODS: Genotyping of the GNAS T393C polymorphism in 196 prostate cancer patients and 200 healthy controls was performed by DNA extraction followed by PCR and restriction analysis. RESULTS: We observed no evidence of effects related to GNAS T393C genotype as demonstrated by a comparison of the genotype distribution in prostate cancer patients and healthy controls, the genotype distribution dependent on grade of the primary diagnosis or data on clinical follow-up. CONCLUSIONS: In conclusion, this study did not demonstrate an association between the GNAS T393C genotype and prostate cancer though such a relationship has been described for other cancer entities.

Is there an association between hospital accreditation and patient satisfaction with hospital care? A survey of 37,000 patients treated by 73 hospitals.

OBJECTIVE: In many countries hospitals are undergoing accreditation as mandatory or voluntary measures. It is believed that accreditation positively influence quality of care and patient satisfaction. This survey aims at assessing the relationship between patient satisfaction and accreditation status. DESIGN: Between January and May 2007, 4 weeks after their discharge, 78 508 patients from 328 departments in 73 hospitals received a validated questionnaire. Data from 36 777 patients (response rate 55%) were available for analyses. MAIN OUTCOME MEASURES: Recommendation rate was used as primary endpoint, which was available from 35 945 patients. To address the clustering of patients within hospitals, we applied univariate and multivariable generalized estimating equations. As covariates we used 'gender' and 'age' at the patient level and the 'number of beds' and 'hospital teaching status' at the hospital level. RESULTS: Overall and not addressing the clustering, 66.3% of all the patients recommend their hospital to others. This recommendation, however, was not related to the accreditation status in the univariate analyses (odds ratio (OR) for accreditation ('yes') and recommendation ('yes') 0.99, 95% confidence interval (CI) 0.85-1.16, P= 0.92). This result was similar in the multivariable regression model adjusted for clustering (OR = 0.98, 95% CI 0.84-1.13, P= 0.74). CONCLUSIONS: Our results support the notion that accreditation is not linked to measurable better quality of care as perceived by the patient. Hospital accreditation may represent a step towards total quality management, but may not be a key factor to quality of care measured by the patient's willingness to recommend.

Impact of immunosuppressive therapy on hepatitis C infection after renal transplantation.

BACKGROUND: Among patients after renal transplantation (NTx), hepatitis C virus (HCV) infection is a risk factor for graft loss and patient death caused by hepatic decompensation. Also, HCV has been implicated in the pathogenesis of glomerular diseases in native and transplanted kidneys. Therefore, the aim of this retrospective cohort study was to determine the effects of the widely used calcineurin inhibitors (CNI) cyclosporine A (CsA) and tacrolimus (Tac) on hepatitis C virus replication, inflammatory activity, development of liver fibrosis, and long-term renal graft function. SUBJECTS AND METHODS: A cohort of 71 patients with HCV infection after kidney transplantation under immunosuppression with either CsA or Tac were analyzed for viral kinetics and serum transaminases. In addition, presence of liver fibrosis was detected by non-invasive measurements using the FibroScan. Graft function was determined biochemically. Patients with interferon therapy prior to transplantation were excluded from the study in order to avoid any impact of the antiviral therapy on outcomes. RESULTS: In the early period after transplantation, hepatitis C viral load was lower in patients treated with Tac as compared to CsA. This effect became negligible 3 months after transplantation. However, hepatic inflammatory activity was reduced in the CsA-treated group. Extent of liver fibrosis was similar in both groups of HCV-infected patients as well as in a control group of non-HCV-infected patients after renal transplantation (NTx), respectively. Renal function and glomerular filtration rate, as calculated by the modification of diet in renal disease (MDRD) formula, were significantly better in patients treated with Tac. CONCLUSIONS: During long-term immunosuppression, the CNIs cyclosporine A versus tacrolimus showed no significant differences in HCV-infected patients after renal transplantation with respect to viral replication and development of liver fibrosis. However, function of the renal graft is significantly better preserved in patients receiving tacrolimus.