Content validation of the International Classification of Functioning, Disability and Health Core Set for stroke from gender perspective using a qualitative approach

BACKGROUND: The extended ICF Core Set for stroke is an application of the International Classification of Functioning, Disability and Health (ICF) of the World Health Organisation (WHO) with the purpose to represent the typical spectrum of functioning of persons with stroke.AIM: The objective of the study is to add evidence to the content validity of the extended ICF Core Set for stroke from persons after stroke taking into account gender perspective.DESIGN AND SETTING: A qualitative study design was conducted by using individual interviews with women and men after stroke in an in- and outpatient rehabilitation setting.METHODS: The sampling followed the maximum variation strategy. Sample size was determined by saturation. Concepts from qualitative data analysis were linked to ICF categories and compared to the extended ICF Core Set for stroke.RESULTS: Twelve women and 12 men participated in 24 individual interviews. In total, 143 out of 166 ICF categories included in the extended ICF Core Set for stroke were confirmed (women: N.=13; men: N.=17; both genders: N.=113). Thirty-eight additional categories that are not yet included in the extended ICF Core Set for stroke were raised by women and men.CONCLUSION: This study confirms that the experience of functioning and disability after stroke shows communalities and differences for women and men. The validity of the extended ICF Core Set for stroke could be mostly confirmed, since it does not only include those areas of functioning and disability relevant to both genders but also those exclusively relevant to either women or men.<br/

Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: The Mild to Moderate Kidney Disease Study

Progressive renal vascular sclerosis is a key feature of chronic kidney disease (CKD). Adiponectin, an adipokine with potent anti-inflammatory and antiatherosclerotic properties, is associated with insulin resistance, type II diabetes and cardiovascular disease. In this study, we evaluated the predictive value of adiponectin for the progression of CKD in patients enrolled in the Mild to Moderate Kidney Disease Study. The primary end point was defined as a doubling of the baseline serum creatinine and/or terminal renal failure in 177 patients who completed a prospective follow-up of 7 years. Patients who reached a progression endpoint (n=65) were significantly older, had higher baseline serum creatinine, proteinuria and adiponectin concentrations and more components of the metabolic syndrome. A gender-stratified Cox model revealed adiponectin in men as a significant predictor of progression after adjustment for age, glomerular filtration rate, and proteinuria. Male patients with adiponectin levels above their ROC analysis-derived optimal cutoff of 4μg/ml had a significantly faster progression than patients below this point. This prospective long-term study in patients with CKD indicates high adiponectin as a novel independent predictor of disease progression in men but not in women. Our observation may be relevant for other conditions of progressive vascular sclerosis and diabetic nephropathy

Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4 Randomized Controlled Trials.

Patients undergoing carotid endarterectomy (CEA) for symptomatic stenosis of the internal carotid artery benefit from early intervention. Heterogeneous data are available on the influence of timing of carotid artery stenting (CAS) on procedural risk. We investigated the association between timing of treatment (0-7 days and &gt;7 days after the qualifying neurological event) and the 30-day risk of stroke or death after CAS or CEA in a pooled analysis of individual patient data from 4 randomized trials by the Carotid Stenosis Trialists' Collaboration. Analyses were done per protocol. To obtain combined estimates, logistic mixed models were applied. Among a total of 4138 patients, a minority received their allocated treatment within 7 days after symptom onset (14% CAS versus 11% CEA). Among patients treated within 1 week of symptoms, those treated by CAS had a higher risk of stroke or death compared with those treated with CEA: 8.3% versus 1.3%, risk ratio, 6.7; 95% confidence interval, 2.1 to 21.9 (adjusted for age at treatment, sex, and type of qualifying event). For interventions after 1 week, CAS was also more hazardous than CEA: 7.1% versus 3.6%, adjusted risk ratio, 2.0; 95% confidence interval, 1.5 to 2.7 (P value for interaction with time interval 0.06). In randomized trials comparing stenting with CEA for symptomatic carotid artery stenosis, CAS was associated with a substantially higher periprocedural risk during the first 7 days after the onset of symptoms. Early surgery is safer than stenting for preventing future stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00190398; URL: http://www.controlled-trials.com. Unique identifier: ISRCTN57874028; URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25337470; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732

Sex-Specific Association of the Putative Fructose Transporter SLC2A9 Variants With Uric Acid Levels Is Modified by BMI

OBJECTIVE—High serum uric acid levels lead to gout and have been reported to be associated with an increased risk of hypertension, obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Recently, the putative fructose transporter SLC2A9 was reported to influence uric acid levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms within this gene with uric acid levels and to determine whether this association is modified by obesity

Association of Adiponectin Gene Polymorphisms With Type 2 Diabetes in an African American Population Enriched for Nephropathy

OBJECTIVE—Polymorphisms in the adiponectin gene (ADIPOQ) have been associated with type 2 diabetes and diabetic nephropathy in type 1 diabetes, in mostly European-derived populations

A genome-wide association meta-analysis on apolipoprotein A-IV concentrations.

Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 (-)  (44)), rs5104 in APOA4 (P = 1.79 × 10(-)(24)) and rs4241819 in KLKB1 (P = 5.6 × 10(-)(14)). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 (-)  (07)). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10(-)(05)). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations

Plasma Concentrations of Afamin Are Associated With Prevalent and Incident Type 2 Diabetes: A Pooled Analysis in More Than 20,000 Individuals.

The human vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). Individual-level baseline ( javax.xml.bind.JAXBElement@f254025 = 20,136) and follow-up data ( javax.xml.bind.JAXBElement@30ded076 = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95% CI 1.12-1.26], javax.xml.bind.JAXBElement@300447f6 = 5.96 × 10 javax.xml.bind.JAXBElement@7b7e80f0 ). Afamin was positively associated with IR assessed by HOMA-IR (β 0.110 [95% CI 0.089-0.132], javax.xml.bind.JAXBElement@5e7fd3d2 = 1.37 × 10 javax.xml.bind.JAXBElement@18e4f50b ). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23-1.38], javax.xml.bind.JAXBElement@a4d3a16 = 3.53 × 10 javax.xml.bind.JAXBElement@53b52af ) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. This pooled analysis in &gt;20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes

Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p>In a genome-wide association scan, the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (<it>PNPLA3</it>) was strongly associated with increased liver fat content. We investigated whether this SNP is associated with the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) in the Japanese population.</p> <p>Methods</p> <p>SNP rs738409 was genotyped by the Taqman assay in 253 patients with NAFLD (189 with nonalcoholic steatohepatitis [NASH] and 64 with simple steatosis) and 578 control subjects. All patients with NAFLD underwent liver biopsy. Control subjects had no metabolic disorders. For a case-control study, the <it>χ</it>²-test (additive model) was performed. Odds ratios (ORs) were adjusted for age, gender, and body mass index (BMI) by using multiple logistic regression analysis with genotypes (additive model), age, gender, and BMI as the independent variables. Multiple linear regression analysis was performed to test the independent effect of risk allele on clinical parameters while considering the effects of other variables (age, gender, and BMI), which were assumed to be independent of the effect of the SNP.</p> <p>Results</p> <p>The risk allele (G-allele) frequency of rs738409 was 0.44 in the control subjects and 0.60 in patients with NAFLD; this shows a strong association with NAFLD (additive model, <it>P </it>= 9.4 × 10^-10). The OR (95% confidence interval) adjusted for age, gender, and BMI was 1.73 (1.25-2.38). Multiple linear regression analysis indicated that the G-allele of rs738409 was significantly associated with increases in aspartate transaminase (AST) (<it>P </it>= 0.00013), alanine transaminase (ALT) (<it>P </it>= 9.1 × 10^-6), and ferritin levels (<it>P </it>= 0.014), and the fibrosis stage (<it>P </it>= 0.011) in the patients with NAFLD, even after adjustment for age, gender, and BMI. The steatosis grade was not associated with rs738409.</p> <p>Conclusions</p> <p>We found that in the Japanese population, individuals harboring the G-allele of rs738409 were susceptible to NAFLD, and that rs738409 was associated with plasma levels of ALT, AST, and ferritin, and the histological fibrosis stage. Our study suggests that <it>PNPLA3 </it>may be involved in the progression of fibrosis in NAFLD.</p

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI<25 kg/m2) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far