Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.

Statins can be associated with myopathy. We have undertaken a genomewide association study (GWAS) to discover and validate genetic risk factors for statin-induced myopathy in a "real-world" setting. One hundred thirty-five patients with statin myopathy recruited via the UK Clinical Practice Research Datalink were genotyped using the Illumina OmniExpress Exome version 1.0 Bead Chip and compared with the Wellcome Trust Case-Control Consortium (n = 2,501). Nominally statistically significant single nucleotide polymorphism (SNP) signals in the GWAS (P T in the SLCO1B1 gene) SNP was genomewide significant in the severe myopathy (creatine kinase > 10 × upper limit of normal or rhabdomyolysis) group (P = 2.55 × 10-9 ; odds ratio 5.15; 95% confidence interval 3.13-8.45). The association with SLCO1B1 was present for several statins and replicated in the independent validation cohorts. The data highlight the role of SLCO1B1 c.521C>T SNP as a replicable genetic risk factor for statin myopathy. No other novel genetic risk factors with a similar effect size were identified

Drug safety of rosiglitazone and pioglitazone in France: a study using the French PharmacoVigilance database

International audienceBackgroundThiazolidinediones (TZDs), rosiglitazone (RGZ) and pioglitazone (PGZ) are widely used as hypoglycemic drugs in patients with type 2 diabetes mellitus. The aim of our study was to investigate the profile of adverse drug reactions (ADRs) related to TZDs and to investigate potential risk factors of these ADRs.MethodsType 2 diabetic patients were identified from the French Database of PharmacoVigilance (FPVD) between 2002 and 2006. We investigated ADR related to TZD, focusing on 4 ADR: edema, heart failure, myocardial infarction and hepatitis corresponding to specific WHO-ART terms.ResultsAmong a total of 99,284 adult patients in the FPVD, 2295 reports concerned type 2 diabetic patients (2.3% of the whole database), with 161 (7%) exposed to TZDs. The frequency of edema and cardiac failure was significantly higher with TZDs than in other patients (18% and 7.4% versus 0.8% and 0.1% respectively, p ConclusionsThiazolidinediones exposure is associated with an increased risk of edema and heart failure in patients with type 2 diabetes even when recommendations for use are respected. In contrast, the risk of hepatic reactions and myocardial infarction with this class of drugs seems to be similar to other hypoglycemic agents

Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccines: A multinational self-controlled case series in Europe

Background: The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk

Pharmacogenomics of statin-related myopathy:Meta-analysis of rare variants from whole-exome sequencing

AIMS:Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. METHODS AND RESULTS:SRM 3-5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3-5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. CONCLUSIONS:In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable

Social inequalities and correlates of psychotropic drug use among young adults: a population-based questionnaire study

<p>Abstract</p> <p>Background</p> <p>Use of psychotropic drugs is widespread in Europe, and is markedly more common in France than elsewhere. Young adults often fare less well than adolescents on health indicators (injury, homicide, and substance use). This population-based study assessed disparities in psychotropic drug use among people aged 18–29 from different socio-occupational groups and determined whether they were mediated by educational level, health status, income, health-related behaviours, family support, personality traits, or disability.</p> <p>Methods</p> <p>A total of 1,257 people aged 18–29, randomly selected in north-eastern France completed a post-mailed questionnaire covering sex, date of birth, height, weight, educational level, occupation, smoking habit, alcohol abuse, income, health-status, diseases, reported disabilities, self-reported personality traits, family support, and frequent psychotropic medication for tiredness, nervousness/anxiety or insomnia. The data were analyzed using the adjusted odds ratios (ORa) computed with logistic models.</p> <p>Results</p> <p>Use of psychotropic drugs was common (33.2%). Compared with upper/intermediate professionals, markedly high odds ratios adjusted for sex were found for manual workers (2.57, 95% CI 1.02–6.44), employees (2.58, 1.11–5.98), farmers/craftsmen/tradesmen (4.97, 1.13–21.8), students (2.40, 1.06–5.40), and housewives (3.82, 1.39–10.5). Adjusting for all the confounders considered reduced the estimates to a pronounced degree for manual workers (adjusted OR 1.49, non-significant) but only slightly for the other socio-occupational groups. The odds ratio for unemployed people did not reach statistical significance. The significant confounders were: sex, not-good health status, musculoskeletal disorders and other diseases, being worried, nervous or sad, and lack of family support (adjusted odds ratios between 1.60 and 2.50).</p> <p>Conclusion</p> <p>There were marked disparities among young adults from different socio-occupational groups. Sex, health status, musculoskeletal diseases, family support, and personality traits were related to use of psychotropic drugs. These factors mediated the higher risk strongly among manual workers and slightly among the other groups.</p

Correlates of opium use: retrospective analysis of a survey of tribal communities in Arunachal Pradesh, India

BACKGROUND: Household survey data of Changlang district, Arunachal Pradesh, were used in the present study to assess the prevalence of opium use among different tribes, and to examine the association between sociodemographic factors and opium use. METHODS: A sample of 3421 individuals (1795 men and 1626 women) aged 15 years and older was analyzed using a multivariate logistic regression model to determine factors associated with opium use. Sociodemographic information such as age, education, occupation, religion, ethnicity and marital status were included in the analysis. RESULTS: The prevalence of opium use was significantly higher (10.6%) among men than among women (2.1%). It varied according to age, educational level, occupation, marital status and religion of the respondents. In both sexes, opium use was significantly higher among Singpho and Khamti tribes compared with other tribes. Multivariate logistic regression indicated that opium use was significantly associated with age, occupation, ethnicity, religion and marital status of the respondents of both sexes. Multivariate rate ratios (MRR) for opium use were significantly higher (4–6 times) among older age groups (≥35 years) and male respondents. In males, the MRR was also significantly higher in respondents of Buddhist and Indigenous religion, while in females, the MRR was significantly higher in Buddhists. Most of the female opium users had taken opium for more than 5 years and were introduced to it by their husbands after marriage. Use of other substances among opium users comprised mainly tobacco (76%) and alcohol (44%). CONCLUSIONS: The study reveals the sociodemographic factors, such as age, sex, ethnicity, religion and occupation, which are associated with opium use. Such information is useful for institution of intervention measures to reduce opium use