Expanded, but not regulated: ambiguity in home-care policy in Ireland

This article argues that home-care policy in Ireland was ambiguous throughout the first decade of the 21st century: policy-makers expanded home care, but failed to develop policies to govern this expanded provision. As a result, home care became more widely available in the absence of a framework to govern access to services and to regulate care providers. We analysed official policy documents, statistics and policy critiques published between 2000 and 2010 in order to understand this incongruity between the expansion of home-care services and the failure to develop policies to govern access to and quality of services. The key factors that motivated home-care expansion in the Irish case were: (1) problems in the acute hospital sector and the perception of home care as a partial solution to these (political blame avoidance) and (2) significant GDP growth (until 2007) that provided politicians with the means to fund expansion in home-care services (political credit claiming). The key factors that inhibited the development of a policy framework to govern home-care services were: (1) weak governance structures in health services and decision-making at national level based on short-term political gain; (2) Ireland's adherence to the liberal welfare state model and concern about uncontrollable care costs in the face of population ageing; (3) until 2010, paucity of attention to home-care issues in the Irish media and (4) weak provider interest representation. The recent budgetary cutbacks in Ireland bring into sharp relief the political expediency of an unregulated domiciliary care sector and absence of entitlements to home care. We conclude that the forces that drive expanded provision are different from drivers of policy to govern home care and that weakness of governance structures and political advantages of the absence of regulation are the main reasons for the lack of standards and entitlement rules.     

Laparoscopic Roux‐en‐Y gastric bypass surgery influenced pharmacokinetics of several drugs given as a cocktail with the highest impact observed for CYP1A2, CYP2C8 and CYP2E1 substrates

There is a lack of information about the changes in drug pharmacokinetics and cytochrome P450 (CYP) metabolism after bariatric surgery. Here, we investigated the effects of laparoscopic Roux‐en‐Y gastric bypass (LRYGB) surgery on pharmacokinetics of nine drugs given simultaneously which may reveal changes in the activities of the main CYPs. Eight obese subjects undergoing LRYGB received an oral cocktail containing nine drugs, substrates of various CYPs: melatonin (CYP1A2), nicotine (CYP2A6), bupropion (CYP2B6), repaglinide (CYP2C8), losartan (CYP2C9), omeprazole (CYP2C19/CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A). The 6‐hours pharmacokinetic profiles in serum and urine of each drug or corresponding metabolite as well as their metabolic ratios were compared before surgery with those at a median 1 year later. LRYGB exerted variable effects on the pharmacokinetics of these drugs. The geometric mean AUC_0‐6 (90% confidence interval) of melatonin, bupropion, repaglinide, chlorzoxazone and midazolam after LRYGB was 27 (19%‐41%), 54 (43%‐67%), 44 (29%‐66%), 160 (129%‐197%) and 74 (62%‐90%) of the pre‐surgery values, respectively. The pharmacokinetics of losartan, omeprazole and dextromethorphan did not change in response to surgery. Nicotine was not detected in serum, while geometric mean of AUC_0‐6 of its metabolite, cotinine, increased by 1.7 times after surgery. There were 3.6‐ and 1.3‐fold increases in the AUC ratios of 6‐hydroxymelatonin/melatonin and hydroxybupropion/bupropion, respectively. The cocktail revealed multiple pharmacokinetic changes occurring after LRYGB with the greatest effects observed for CYP1A2, CYP2C8 and CYP2E1 substrates. Future studies should be focused on CYP1A2, CYP2A6, CYP2C8 and CYP2B6 to clarify the changes in activities of these enzymes after LRYGB.     

Novel genetic susceptibility loci for diabetic end-stage renal disease identified through robust naive Bayes classification

Aims/hypothesis

Diabetic nephropathy is a major diabetic complication, and diabetes is the leading cause of end-stage renal disease (ESRD). Family studies suggest a hereditary component for diabetic nephropathy. However, only a few genes have been associated with diabetic nephropathy or ESRD in diabetic patients. Our aim was to detect novel genetic variants associated with diabetic nephropathy and ESRD.

Methods

We exploited a novel algorithm, ‘Bag of Naive Bayes’, whose marker selection strategy is complementary to that of conventional genome-wide association models based on univariate association tests. The analysis was performed on a genome-wide association study of 3,464 patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study and subsequently replicated with 4,263 type 1 diabetes patients from the Steno Diabetes Centre, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK collection (UK–Republic of Ireland) and the Genetics of Kidneys in Diabetes US Study (GoKinD US).

Results

Five genetic loci (WNT4/ZBTB40-rs12137135, RGMA/MCTP2-rs17709344, MAPRE1P2-rs1670754, SEMA6D/SLC24A5-rs12917114 and SIK1-rs2838302) were associated with ESRD in the FinnDiane study. An association between ESRD and rs17709344, tagging the previously identified rs12437854 and located between the RGMA and MCTP2 genes, was replicated in independent case–control cohorts. rs12917114 near SEMA6D was associated with ESRD in the replication cohorts under the genotypic model (p?<?0.05), and rs12137135 upstream of WNT4 was associated with ESRD in Steno.

Conclusions/interpretation

This study supports the previously identified findings on the RGMA/MCTP2 region and suggests novel susceptibility loci for ESRD. This highlights the importance of applying complementary statistical methods to detect novel genetic variants in diabetic nephropathy and, in general, in complex diseases.     

Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes

Aims/hypothesis

An abnormal urinary albumin excretion rate (AER) is often the first clinically detectable manifestation of diabetic nephropathy. Our aim was to estimate the heritability and to detect genetic variation associated with elevated AER in patients with type 1 diabetes.

Methods

The discovery phase genome-wide association study (GWAS) included 1,925 patients with type 1 diabetes and with data on 24 h AER. AER was analysed as a continuous trait and the analysis was stratified by the use of antihypertensive medication. Signals with a p value <10^?4 were followed up in 3,750 additional patients with type 1 diabetes from seven studies.

Results

The narrow-sense heritability, captured with our genotyping platform, was estimated to explain 27.3% of the total AER variability, and 37.6% after adjustment for covariates. In the discovery stage, five single nucleotide polymorphisms in the GLRA3 gene were strongly associated with albuminuria (p?<?5?×?10^?8). In the replication group, a nominally significant association (p?=?0.035) was observed between albuminuria and rs1564939 in GLRA3, but this was in the opposite direction. Sequencing of the surrounding genetic region in 48 Finnish and 48 UK individuals supported the possibility that population-specific rare variants contribute to the synthetic association observed at the common variants in GLRA3. The strongest replication (p?=?0.026) was obtained for rs2410601 between the PSD3 and SH2D4A genes. Pathway analysis highlighted natural killer cell mediated immunity processes.

Conclusions/interpretation

This study suggests novel pathways and molecular mechanisms for the pathogenesis of albuminuria in type 1 diabetes.     

A former career as a male elite athlete—does it protect against type 2 diabetes in later life?

Aims/hypothesis

The aim of this study was to determine the prevalence of impaired glucose regulation in male Finnish former elite athletes and age- and area-matched controls. We hypothesised that vigorous physical activity during young adulthood protects from disturbances in glucose regulation in later life.

Methods

In 2008, 392 former male elite athletes (mean age 72.7?±?6.1 years) and 207 controls (mean age 71.6?±?5.6 years) participated in a clinical study (participation rate: 50.6%). The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Participants without a history of diabetes (n?=?537) underwent a 2 h 75 g OGTT. Current volume of leisure-time physical activity (LTPA) was determined by self-reported questionnaires and expressed in metabolic equivalent hours (MET-h). Data on reimbursable diabetes medication from participants and non-participants was obtained from the register of the Finnish Social Insurance Institution.

Results

Compared with the controls, the former elite athletes had a significantly lower risk of type 2 diabetes (OR 0.72, 95% CI 0.53, 0.98). The risk of type 2 diabetes decreased with increased LTPA volume (OR 0.98, 95% CI 0.97, 0.99 per 1 MET-h/week). The former elite athletes also had a significantly lower risk of impaired glucose tolerance (IGT) than the controls (OR 0.58, 95% CI 0.38, 0.87).

Conclusions/interpretation

A former career as an elite athlete protected from both type 2 diabetes and IGT in later life. In addition, the volume of current LTPA was inversely associated with the prevalence of type 2 diabetes.