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Payne K.,University of Manchester | Fargher E.A.,Bangor University | Roberts S.A.,University of Manchester | Tricker K.,University of Manchester | And 4 more authors.
Value in Health | Year: 2011

Objective: The study compared the preferences of patients and health-care professionals for the key attributes of a pharmacogenetic testing service to identify a patient's risk of developing a side effect (neutropenia) from the immunosuppressant, azathioprine. Methods: A discrete choice experiment was posted to a sample of patients (n=309) and healthcare professionals (HCPs) (n=410), as part of the TARGET study. Five attributes, with four levels each, described the service as follows: level of information given; predictive ability of the test; how the sample is collected; turnaround time for a result; who explains the test result. Data from each sample were first analyzed separately and responses were compared by 1) identifying the impact of the scale parameter, and 2) estimating marginal rates of substitution. Results: The final analysis included 159 patients and 138 HCPs (50% & 34% response rates). Estimated attribute coefficients from the patient and HCP sample differed in size, after taking into account the impact of the scale parameter. Patients and HCPs had similar preferences for predictive accuracy of the test and were willing to wait 2 days for a 1% improvement in test accuracy. Patients preferred to obtain more information and were willing to wait 19 days compared to 8 days for HCPs for providing higher levels of information. Conclusions: Patients demanded accurate and timely information from health-care professionals about why it was necessary to have a pharmacogenetic test and what the test results mean. In contrast, health-care professionals appear to focus more exclusively or entirely upon the predictive accuracy and waiting time for a test result. Copyright © 2011, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.


Heazell A.E.P.,University of Manchester | Heazell A.E.P.,Manchester Biomedical Research Center | Bernatavicius G.,University of Manchester | Warrander L.,University of Manchester | And 2 more authors.
Reproductive Sciences | Year: 2012

Metabolomics offers a powerful holistic approach to examine the metabolite composition of biofluids to identify disruptions present in disease. We used ultra performance liquid chromatography-mass spectroscopy on the maternal serum obtained in the third trimester to address the hypothesis that pregnancies ending in poor outcomes (small for gestational age infant, preterm birth, or neonatal intensive care admission, n = 40) would have a different maternal serum metabolic profiles to matched healthy pregnancies (n = 40). Ninety-eight identified metabolic features differed between normal and poor pregnancy outcomes. Classes of metabolites perturbed included free fatty acids, glycerolipids, progesterone metabolites, sterol lipids, vitamin D metabolites, and sphingolipids; these highlight potential molecular mechanisms associated with pregnancy complications in the third trimester linked by placental dysfunction. In this clinical setting, metabolomics has the potential to describe differences in fetoplacental and maternal metabolites in pregnancies with poor pregnancy outcomes compared with controls. © The Author(s) 2012.


Rutter M.K.,University of Manchester | Rutter M.K.,Manchester Biomedical Research Center | Prais H.R.,University of Manchester | Prais H.R.,Manchester Biomedical Research Center | And 23 more authors.
Diabetic Medicine | Year: 2011

Aims To compare the renal effects of low- vs. high-dose atorvastatin in patients with Type 2 diabetes mellitus and optimally managed early renal disease.Methods We compared the 2-year progression of nephropathy in a double-blind randomized controlled trial of atorvastatin 80 mg/day (n = 60) vs. 10 mg/day (n = 59) in patients with Type 2 diabetes with microalbuminuria or proteinuria [mean (sd): age 64 years (10 years); HbA1c 7.7% (1.3%), 61 mmol/mol (10 mmol/mol); blood pressure 131/73 mmHg; renin-angiotensin system blocker use > 80%; dual blockade > 67%] recruited from diabetes clinics in Greater Manchester.Results Over (mean) 2.1 years of follow-up, the Modification of Diet in Renal Disease estimated glomerular filtration rate declined by 3 ml min-1 1.73 m-2 in the combined group. The mean (95% CI) between-group difference during follow-up was not significant [2.2 ml min-1 1.73 m-2 (-1.1 to 5.4 ml min-1 1.73 m-2), P = 0.20] after adjusting for baseline differences in renal function; positive difference favours 80 mg dose. Similarly, there was no significant difference in creatinine clearance by Cockcroft and Gault [2.5 ml/min (-2.4 to 7.3 ml/min), P = 0.32]; serum creatinine/24-h urine collections [4.0 ml/min (-4.8 to 12.7 ml/min), P = 0.38]; cystatin C (P = 0.69); or 24-h urine protein or albumin excretion (P = 0.92; P = 0.93). We recorded no significant between-group differences in deaths or adverse events.Conclusions In patients with Type 2 diabetes with early renal disease, we found no statistical difference in renal function between those taking high- or low-dose atorvastatin over 2 years. We cannot exclude a beneficial effect of < 1.6 ml min-1 1.73 m-2 year-1 on Modification of Diet in Renal Disease estimated glomerular filtration rate, or if blood pressure management or if renin-angiotensin system blocker use had not been optimized. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.

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