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Wolowacz S.E.,Manchester Business Park | Samuel M.,Manchester Business Park | Brennan V.K.,Business and Conference Center | Jasso-Mosqueda J.-G.,Sanofi S.A. | Van Gelder I.C.,University of Groningen
Europace | Year: 2011

Atrial fibrillation (AF) is the most common cardiac arrhythmia, its prevalence increasing markedly with age. Atrial fibrillation is strongly associated with increased risk of morbidity, including stroke and thromboembolism. There is growing awareness of the economic burden of AF due to ageing populations and constrained public finances. A systematic review was performed (19902009). Cost studies for AF or atrial flutter were included; acute-onset and post-operative AF were excluded. Total, direct, and indirect costs were extracted. Of 875 records retrieved, 37 studies were included. The cost of managing individual AF patients is high. Direct-cost estimates ranged from 2000 to 14 200 per patient-year in the USA and from €450 to 3000 in Europe. This is comparable with other chronic conditions such as diabetes. The direct cost of AF represented 0.92.4 of the UK health-care budget in 2000 and had almost doubled over the previous 5 years. Inpatient care accounted for 5070 of annual direct costs. In the USA, AF hospitalizations alone cost ∼6.65 billion in 2005. In this first systematic review of the economic burden of AF, hospitalizations consistently represented the major cost driver. Costs and hospitalizations attributable to AF have increased markedly over recent decades and are expected to increase in future due to ageing populations. © 2011 The Author.


Hall K.,Monash University | Lee T.-H.,Monash University | Mechler A.I.,La Trobe University | Swann M.J.,Manchester Business Park | Aguilar M.-I.,Monash University
Scientific Reports | Year: 2014

The disruption of membranes by antimicrobial peptides is a multi-state process involving significant structural changes in the phospholipid bilayer. However, direct measurement of these membrane structural changes is lacking. We used a combination of dual polarisation interferometry (DPI), surface plasmon resonance spectroscopy (SPR) and atomic force microscopy (AFM) to measure the real-time changes in membrane structure through the measurement of birefringence during the binding of magainin 2 (Mag2) and a highly potent analogue in which Ser8, Gly13 and Gly18 has been replaced with alanine (Mag-A). We show that the membrane bilayer undergoes a series of structural changes upon peptide binding before a critical threshold concentration is reached which triggers a significant membrane disturbance. We also propose a detailed model for antimicrobial peptide action as a function of the degree of bilayer disruption to provide an unprecedented in-depth understanding of the membrane lysis in terms of the interconversion of different membrane conformational states in which there is a balance between recovery and lysis.


Barrett A.,Manchester Business Park | Clark M.,RTI Health Solutions | DeMuro C.,RTI Health Solutions | Esser D.,Boehringer Ingelheim GmbH
European Respiratory Journal | Year: 2013

Which proxy-reported outcome measures have been developed for use with children aged 6 years and younger to assess asthma symptoms, asthma control, and asthma-specific health-related quality of life, and do these questionnaires


Stull D.E.,Manchester Business Park | Houghton K.,Manchester Business Park
Value in Health | Year: 2013

Objectives: To present a step-by-step example of the examination of heterogeneity within clinical trial data by using a growth mixture modeling (GMM) approach. Methods: Secondary data from a longitudinal double-blind clinical drug study were used. Patients received enalapril or placebo and were followed for 2 years during the drug component, followed by a 3-year postdrug component. Primary variables of interest were creatinine levels during the drug component and number of hospitalizations in the postdrug component. Latent growth modeling (LGM) methods were used to examine the treatment response variability in the data. GMM methods were applied where substantial variability was found to identify latent (unobserved) subsets of differential responders, using treatment groups as known classes. Post hoc analyses were applied to characterize emergent subgroups. Results: LGM methods demonstrated a large variability in creatinine levels. GMM methods identified two subsets of patients for each treatment group. Placebo class 2 (7.0% of the total sample) and enalapril class 2 (8.5%) include individuals whose creatinine levels start at 1.114 mg/dl and 1.108 mg/dl, respectively, and show worsening (slopes: 0.023 and 0.017, respectively). Placebo class 1 (43.1%) and enalapril class 1 (41.4%) individuals start with lower creatinine levels (1.082 and 1.083 mg/dl, respectively) and show very minimal change (0.008 and 0.003, respectively). Post hoc analyses revealed significant differences between placebo/enalapril class 1 and placebo/enalapril class 2 in terms of New York Heart Association functional ability, depression, functional impairment, creatinine levels, mortality, and hospitalizations. Conclusions: GMM methods can identify subsets of differential responders in clinical trial data. This can result in a more accurate understanding of treatment effects. © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.


Brodtkorb T.-H.,RTI Health Solutions | Bell M.,Manchester Business Park | Irving A.H.,University of Sydney | Laramee P.,Social and Epidemiological Research Program
CNS Drugs | Year: 2016

Aim: To evaluate costs and health outcomes of nalmefene plus psychosocial support, compared with psychosocial intervention alone, for reducing alcohol consumption in alcohol-dependent patients, specifically focusing on societal costs related to productivity losses and crime. Methods: A Markov model was constructed to model costs and health outcomes of the treatments over 5 years. Analyses were conducted for nalmefene's licensed population: adults with both alcohol dependence and high or very high drinking-risk levels (DRLs) who do not require immediate detoxification and who have high or very high DRLs after initial assessment. The main outcome measure was cost per quality-adjusted life-year (QALY) gained as assessed from a UK societal perspective. Alcohol-attributable productivity loss, crime and health events occurring at different levels of alcohol consumption were taken from published risk-relation studies. Health-related and societal costs were drawn from public data and the literature. Data on the treatment effect, as well as baseline characteristics of the modelled population and utilities, came from three pivotal phase 3 trials of nalmefene. Results: Nalmefene plus psychosocial support was dominant compared with psychosocial intervention alone, resulting in QALYs gained and reduced societal costs. Sensitivity analyses showed that this conclusion was robust. Nalmefene plus psychosocial support led to per-patient reduced costs of £3324 and £2483, due to reduced productivity losses and crime events, respectively. Conclusion: Nalmefene is cost effective from a UK societal perspective, resulting in greater QALY gains and lower costs compared with psychosocial support alone. Nalmefene demonstrates considerable public benefits by reducing alcohol-attributable productivity losses and crime events in adults with both alcohol dependence and high or very high DRLs who do not require immediate detoxification and who have high or very high DRLs after initial assessment. © 2016 Springer International Publishing Switzerland.


Roskell N.S.,Manchester Business Park | Samuel M.,Manchester Business Park | Noack H.,Boehringer Ingelheim | Monz B.U.,Boehringer Ingelheim GmbH
Europace | Year: 2013

Aims Clinical trials have shown that anticoagulation with vitamin K antagonists (VKAs), e.g. warfarin, decreases the risk of stroke in patients with atrial fibrillation (AF); however, increased bleeding risk is one of the safety concerns. The primary objective was to conduct a systematic review of the published literature, assessing the risk of major bleeding and mortality in patients with AF treated with VKAs. Methods and resultsOnline searches of MEDLINE, EMBASE, BIOSIS, and the Cochrane Library were performed to a pre-specified protocol from 1960 to March 2012 for randomized controlled trials (RCTs) and from January 1990 to March 2012 for observational studies. A total of 47 studies (16 RCTs and 31 observational studies) were included. Cumulative follow-up was 61 563 patient-years for RCTs and 484 241 patient-years for observational studies. The overall median incidence of major bleeding was 2.1 per 100 patient-years (range, 0.9-3.4 per 100 patient-years) for RCTs and 2.0 per 100 patient-years (range, 0.2-7.6 per 100 patient-years) for observational studies. With study year as a proxy for changing management patterns, some evidence of bleeding rates and/or their reporting increasing over time was noted. Mortality rates from observational studies were inadequately reported to allow comparison with those from RCT data. Conclusion The median rate of major bleeding in observational studies and RCTs is similar. The larger heterogeneity in bleeding rates observed in a real-life setting could reflect a high variability in standard of care of patients on VKAs and/or methodological differences between observational studies and/or variability in data sources. © 2012 The Author.


Curran S.A.,Cardiff Metropolitan University | Hirons R.,Manchester Business Park
Prosthetics and Orthotics International | Year: 2012

In the last 25 years, the continuous evolution in the design of prostheses for individuals with transfemoral and transtibial amputations has been remarkable. Mirroring this development is the dependency and expectancy of the prosthesis technology by the athletes, coaches and other personnel involved in creating Paralympians of today and the future. Össur is recognised as a leader in designing innovative prosthetic products that have contributed worldwide to developing leading Paralympians. The opening section of this article presents an overview of the new Össur products for 2012. Discussion is also focussed on how Össur's high-function prosthetic products are integrated into an athlete's training regime. With involvement of the clinical team discussion is also expanded to recognise the important contribution coaching staff has on optimising performance of a Paralympian's training regime. The dialogue continues with a viewpoint on whether Oscar Pistorius, the face of Össur who wears Flex-Foot Cheetah blades, should participate in the Olympics and Paralympics. While the conclusion of this article may leave more questions than answers, the technology and products offered by Össur provide for a credible foundation and preparation for future challenges beyond the London 2012 Paralympic Games. © 2012 The International Society for Prosthetics and Orthotics.


Crumbleholme T.,Manchester Business Park
IET Seminar Digest | Year: 2015

Presents a collection of slides covering the following: pumps; fault signal; workforce management information; and data quality.


Beard S.M.,RTI Health Solutions | Von Scheele B.G.,RTI Health Solutions | Nuki G.,University of Edinburgh | Pearson I.V.,Manchester Business Park
European Journal of Health Economics | Year: 2014

Our objective was to evaluate data on the cost-effectiveness of febuxostat compared with standard clinical practice with allopurinol in patients with gout that was presented to the Scottish Medicines Consortium (SMC) in 2010. A Markov health-state model estimated the direct health-related costs and clinical benefits expressed as quality-adjusted life-years (QALYs). Adults with chronic gout and established hyperuricaemia received treatment sequences of daily doses of allopurinol 300 mg alone or allopurinol 300 mg followed by febuxostat 80 mg/120 mg. The proportion of patients achieving the target serum uric acid (sUA) level of less than 6 mg/dl (0.36 mmol/l) was linked to the utility per sUA level to generate an incremental cost-effectiveness ratio (ICER). Second-line therapy with febuxostat 80 mg/120 mg versus with allopurinol alone resulted in an ICER of £3,578 per QALY over a 5-year time horizon. Additional univariate analyses showed that ICER values were robust and ranged from £2,550 to £7,165 per QALY when different parameters (e.g., low-and high-dose allopurinol titrations and variations in treatment-induced flare rates) were varied. Febuxostat reduces sUA below the European League Against Rheumatism target of 0.36 mmol/l (6 mg/dl) in significantly more patients with gout than allopurinol in its most frequently prescribed dose of 300 mg per day. The SMC accepted febuxostat as cost-effective as a suitable second-line option for urate-lowering therapy for the treatment of patients with chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history or presence of tophus and/or gouty arthritis) when treatment with allopurinol was inadequate, not tolerated, or contraindicated. © Springer-Verlag 2013.


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