Estimated GFR and the Effect of Intensive Blood Pressure Lowering after Acute Intracerebral Hemorrhage

Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP 90, 60-90, and <60 mL/min/1.73 m2, respectively). Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs

The value of gene expression profiles using micoarrays for the individualisation of adjuvant therapy after surgery for breast cancer

: Gene-expression profiles are a promising development in determining the prognosis of patients with primary breast cancer. They accurately assess the risk on distant recurrence of disease and show if the patient might benefit from adjuvant therapy after surgery thus minimising the risk of distant metastases. Three clinically relevant profiles on prognosis have now been published, two of which come from the Netherlands, and whose results are an improvement on those using traditional clinical parameters i.e. the St. Gallen and the National Institutes of Health criteria. These gene-expression profiles mean that 25-40% of patients need no longer undergo adjuvant systemic therapy (chemotherapy and/or endocrine therapy). Although the risk-stratifying power of these profiles has been established, their power in predicting the response of the patients to adjuvant systemic therapy still awaits scientific proo

The use of equivalent annual cost for cost benefit analyses in flood risk reduction strategies

In many parts of the world, flooding is a big risk. There are numerous strategies to reduce flood risk. The amount of flood risk reduction strategies grows exponentially with the amount of possible measures that can be implemented and possible timings when measures can be implemented. In this paper, the use of a financial method called “equivalent annual cost” (EAC) is assessed to reduce that number of strategies and evaluate cost-optimal strategies. The use of EAC allows the comparison between short-term and long-term measures by expressing them into an annual interest weighted expected expenditure. As soon as a measure has to be implemented (i.e. the annual risk becomes too large or the safety standards are exceeded), the EAC for all combinations of measures is determined and the combination is implemented with the lowest EAC. This almost leads to cost-optimal flood risk reduction strategies that, by manual optimization, can be improved further. A case study has also been performed in the Hollandsche IJssel which proved the use of EAC. Here it has led to cost-optimal flood risk reduction strategies. The method is tested in one case and it is recommended to apply and test it in other cases as well

Identification and analysis of inherited retinal disease genes

Inherited retinal diseases display a very high degree of clinical and genetic heterogeneity, which poses challenges in identifying the underlying defects in known genes and in identifying novel retinal disease genes. Here, we outline the state-of-the-art techniques to find the causative DNA variants, with special attention for next-generation sequencing which can combine molecular diagnostics and retinal disease gene identification

" On the Shoulders of a giant " : W.F Mandle and the foundations of sports history in Austria

BACKGROUND: In genome-wide association studies (GWAS) five putative risk loci are associated with intracranial aneurysm. As brain arteriovenous malformations (AVM) and intracranial aneurysms are both intracranial vascular diseases and AVMs often have associated aneurysms, we investigated whether these loci are also associated with sporadic brain AVM. METHODS: We included 506 patients (168 Dutch, 338 American) and 1548 controls, all Caucasians. Controls had been recruited as part of previous GWAS. Dutch patients were genotyped by KASPar assay and US patients by Affymetrix SNP 6.0 array. Associations in each cohort were tested by univariable logistic regression modelling, with subgroup analysis in 205 American cases with aneurysm data. Meta-analysis was performed by a Mantel-Haenszel fixed-effect method. RESULTS: In the Dutch cohort none of the single nucleotide polymorphisms (SNPs) were associated with AVMs. In the American cohort, genotyped SNPs near SOX-17 (OR 0.74; 95% CI 0.56-0.98), RBBP8 (OR 0.76; 95% CI 0.62-0.94) and an imputed SNP near CDKN2B-AS1 (OR 0.79; 95% CI 0.64-0.98) were significantly associated with AVM. The association with SNPs near SOX-17 and CDKN2B-AS1 but not RBBP8 were strongest in patients with AVM with associated aneurysms. In the meta-analysis we found no significant associations between allele frequencies and AVM occurrence, but rs9298506, near SOX-17 approached statistical significance (OR 0.77; 95% CI 0.57-1.03, p=0.08). CONCLUSIONS: Our meta-analysis of two Caucasian cohorts did not show an association between five aneurysm-associated loci and sporadic brain AVM. Possible involvement of SOX-17 and RBBP8, genes involved in cell cycle progression, deserves further investigation