Manchester Biomedical Research Center

United Kingdom

Manchester Biomedical Research Center

United Kingdom
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Hermansen P.,University of Manchester | Hermansen P.,Manchester Biomedical Research Center | Freemont T.,University of Manchester | Freemont T.,Manchester Biomedical Research Center
Diagnostic Histopathology | Year: 2017

Normal synovial fluid consists of a transudate of plasma from synovial blood vessels supplemented with high molecular weight lipid and saccharide-rich molecules. This produces a paucicellular, viscous fluid, which behaves like a tissue. In primary (e.g. rheumatoid disease) and secondary (e.g. septic and crystal-induced) inflammatory arthropathies, changes occur to the cell numbers and cell type in the fluid forming the basis of a diagnostic test. The diagnostic value is enhanced by the appearance of endogenous and exogenous particles, particularly those associated with degenerative, crystal-induced, and prosthesis-associated arthropathies (e.g. fibrin, cartilage, crystals, metal and plastic). Cells and particles can be characterised under the microscope leading to a simple, inexpensive, “cytological” test for every type of joint disease. © 2017

Buchan I.E.,University of Manchester | Buchan I.E.,Manchester Biomedical Research Center | Kontopantelis E.,University of Manchester | Kontopantelis E.,Manchester Biomedical Research Center | And 5 more authors.
Journal of Epidemiology and Community Health | Year: 2017

Background Social, economic and health disparities between northern and southern England have persisted despite Government policies to reduce them. We examine long-term trends in premature mortality in northern and southern England across age groups, and whether mortality patterns changed after the 2008- 2009 Great Recession. Methods Population-wide longitudinal (1965-2015) study of mortality in England's five northernmost versus four southernmost Government Office Regions - halves of overall population. Main outcome measure: directly age-sex adjusted mortality rates; northern excess mortality (percentage excess northern vs southern deaths, age-sex adjusted). Results From 1965 to 2010, premature mortality (deaths per 10 000 aged <75 years) declined from 64 to 28 in southern versus 72 to 35 in northern England. From 2010 to 2015 the rate of decline in premature mortality plateaued in northern and southern England. For most age groups, northern excess mortality remained consistent from 1965 to 2015. For 25-34 and 35-44 age groups, however, northern excess mortality increased sharply between 1995 and 2015: from 2.2% (95% CI -3.2% to 7.6%) to 29.3% (95% CI 21.0% to 37.6%); and 3.3% (95% CI -1.0% to 7.6%) to 49.4% (95% CI 42.8% to 55.9%), respectively. This was due to northern mortality increasing (ages 25-34) or plateauing (ages 35-44) from the mid-1990s while southern mortality mainly declined. Conclusions England's northern excess mortality has been consistent among those aged <25 and 45+ for the past five decades but risen alarmingly among those aged 25-44 since the mid-90s, long before the Great Recession. This profound and worsening structural inequality requires more equitable economic, social and health policies, including potential reactions to the England-wide loss of improvement in premature mortality. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017.

Oldroyd A.,University of Manchester | Oldroyd A.,Manchester Biomedical Research Center | Lilleker J.,Greater Manchester Neurosciences Center | Chinoy H.,Salford Royal NHS Foundation Trust
Clinical Medicine, Journal of the Royal College of Physicians of London | Year: 2017

The idiopathic infl ammatory myopathies are a group of conditions characterised by infl ammation of muscles (myositis) and other body systems. The diagnosis can be challenging because of the many potential clinical features and extra-muscular manifestations, which may be seemingly unrelated. An accurate diagnosis requires up-To-date understanding of the clinical manifestations, different clinical subtypes and appropriate interpretation of investigations, including newly described serological subtypes. This review will detail the approach to the diagnosis of an idiopathic infl ammatory myopathy, based on up-To-date knowledge. The recently updated classifi cation criteria and treatment options will also be described.

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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