Assessment of drug-drug interactions in the prescription of elderly patients on cardiovascular drugs

Background: Cardiovascular disease is one of the major causes of mortality and morbidity in a developing country like India. These patient’s prescription contains multiple drugs to reduce the mortality and morbidity and they also contain drugs for treatment of co morbidities leading to polypharmacy. The main objective of the study was to identify the pattern of drug- drug interaction (DDI) in patients on cardiovascular drugs with various co existing morbidities.Methods: This study was conducted in the Department of General Medicine of a tertiary care center. Prescription of 200 patients were analysed for demographic details like gender, age, comorbidities and drugs prescribed. DDI were assessed using Micromedex software.Results: In this study, conducted on the prescription of 200 elderly patients, 13 (66%) prescription had 408 DDI, of which 158 (39%) were major, 246 (60%) were moderate and 1 (0.02%) was contraindicated and 3 (0.007%) were minor.Conclusions: It can be concluded from the present study that the risk of DDI increases with the increase in number of drugs in the prescription and there is increase in number of drugs in the prescription with the increase in number of co morbidities. The antiplatelet and anticoagulant group of drugs were responsible for majority of DDI, followed by antihypertensives and hypoglycaemic agents. Most of these DDI could be avoided with slight modification in the dosage regimen based on the pharmacokinetics and pharmacodynamics of the drug

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)