156 research outputs found

    Prucalopride for the treatment of women with chronic constipation in whom standard laxative regimens have failed to provide adequate relief

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    © Queen’s Printer and Controller of HMSO 2011This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of prucalopride for the treatment of women with chronic constipation in whom standard laxative regimens have failed to provide adequate relief. The ERG report is based on the manufacturer's submission (MS) to the National Institute for Health and Clinical Excellence as part of the single technology appraisal process. In the submission, quality-of-life data [Patient Assessment of Constipation Quality of Life (PAC-QOL) and Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaires] from trials of prucalopride were extrapolated to EQ-5D (European Quality of Life-5 Dimensions) data and used to inform effectiveness in an economic model. Response rates to prucalopride were derived from observed response rates in trials, defined as the proportion of patients achieving an average of three or more spontaneous complete bowel movements over the 4- or 12-week trial periods. Adult (18-64 years) and elderly (≄ 65 years) patients were considered separately in the model. Cost-effectiveness was determined from estimated improvements in EQ-5D and anticipated response rates, adjusted for baseline severity of chronic constipation. The ERG considered that the patients participating in these trials were not representative of those in the licensed indication. They were not all refractory to laxatives, and baseline EQ-5D scores showed a large spread in quality of life, with many patients experiencing little baseline dissatisfaction. The mapping of quality-of-life data from trials (PAC-QOL and PAC-SYM data) to EQ-5D was unclear and invalidated. The assumption of the long-term effectiveness and safety of prucalopride to 1 year was considered unjustified. There was no justification or sources given for coefficients used to predict effectiveness in the economic model, and no costs other than the cost of prucalopride were incorporated into the model. Owing to the many areas of uncertainty, particularly the effectiveness of prucalopride in the licensed patient group and its long-term effectiveness and safety, it was considered that the MS provided no evidence for whether prucalopride is effective or not in women with laxative-refractory chronic constipation. Further subgroup analysis of the actual patient group of interest may have better guided decision-making. However, long-term efficacy data, with validated estimates of quality of life incorporated in a well-founded model, would be important for an evidence-based judgement to be made

    Insulin administration and rate of glucose appearance in people with type 1 diabetes.

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    OBJECTIVE: To assess whether prandial insulin, in addition to basal insulin, has an effect on the rate of glucose appearance from a meal in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: The rate of glucose appearance from a mixed meal (Ra(meal)) was investigated in six adult (aged 24 +/- 2 years), lean (BMI 23.6 +/- 1.5 kg/m(2)) subjects with well-controlled type 1 diabetes (duration 7.9 +/- 6.9 years, A1C 7.6 +/- 0.9%) with/without prandial insulin. Actrapid was infused to maintain euglycemia before meals were consumed. Subjects consumed two identical meals on separate occasions, and Ra(meal) was measured using a dual isotope method. [6,6-(2)H(2)]glucose was incorporated into the meal (0.081 g/kg body wt), and a primed constant/variable rate infusion of [1,2,3,4,5,6,6-(2)H(2)]glucose was administered. In the tests with prandial insulin, an additional bolus dose of Actrapid was given 20 min before the meal at 0.1 units/kg body wt. RESULTS: Insulin concentration with prandial insulin was significantly higher than during basal insulin studies (119 +/- 16 vs. 66 +/- 15 pmol/l, P = 0.03 by paired t test). Despite differences in insulin concentration, there were no differences in total glucose appearance (3,398 +/- 197 vs. 3,307 +/- 343 micromol/kg) or time taken for 25% (33.1 +/- 3.3 vs. 31.7 +/- 3.5 min), 50% (54.6 +/- 3.5 vs. 54.1 +/- 4.7 min), and 75% (82.9 +/- 7.1 vs. 82.8 +/- 5.8 min) of total glucose appearance. The fraction of the glucose dose appearing in the circulation was the same for basal (73 +/- 8%) and prandial (75 +/- 4%) study days. CONCLUSIONS: These results suggest that meal glucose appearance is independent of prandial insulin concentration in people with type 1 diabetes

    A systematic review of positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) for the diagnosis of breast cancer recurrence.

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    addresses: West Midlands Health Technology Assessment Collaboration, Unit of Public Health, Epidemiology & Biostatistics, University of Birmingham, Birmingham, UK.types: Journal Article; Research Support, N.I.H., Extramural; ReviewPublished version. Copyright © 2010 NIHR Health Technology Assessment ProgrammeBreast cancer (BC) accounts for one-third of all cases of cancer in women in the UK. Current strategies for the detection of BC recurrence include computed tomography (CT), magnetic resonance imaging (MRI) and bone scintigraphy. Positron emission tomography (PET) and, more recently, positron emission tomography/computed tomography (PET/CT) are technologies that have been shown to have increasing relevance in the detection and management of BC recurrence

    Leisure, refuge and solidarity:messages in visitors’ books as microforms of travel writing

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    Visitors’ books not only trace developments in modern tourism, but they also reveal changes in the socio-cultural and language attitudes of travellers from all walks of life over prolonged periods of time. This article investigates messages in visitors’ books from Wales from the mid-nineteenth century up to the present and argues for their recognition as microforms of travel writing. Despite their brevity, entries in visitors’ books are a highly complex form of travel writing particularly in the inscribers’ self-fashioning of identity for future readers. The article examines how writerly choices are not only directly rooted in the discourse of travel, but also in socio-political circumstances in the individual travellers’ countries of origin and their travel destinations

    Small Change: Economics and the British coin-tree

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    This is the accepted manuscript for the following article: Ceri Houlbrook, “Small Change: Economics and the British coin-tree”, Post Medieval Archaeology, Vol. 49(1), June 2015. The final published version can be found at: http://www.tandfonline.com/doi/full/10.1179/0079423615Z.00000000074 © Society for Post-Medieval Archaeology 2015Throughout the c.2000 year period coins have been circulated in Britain, they have also been ritually employed, most notably as votive deposits. Focusing specifically on the understudied custom of the British coin-tree, whereby coins are ritually embedded into the barks of trees, this paper considers the coin’s role and applicability as a deposit. It aims to demonstrate that our understanding of the coin’s past, present, and future ritual employment is not only aided by a consideration of economics and the coin’s secular function; it would be utterly incomplete without it.Peer reviewedFinal Accepted Versio

    Practitioner review: Treatments for Tourette syndrome in children and young people: a systematic review

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    Background:Tourette syndrome (TS) and chronic tic disorder (CTD) affect 1–2% of children and young people, but the most effective treatment is unclear. To establish the current evidence base, we conducted a systematic review of interventions for children and young people. Methods:Databases were searched from inception to 1 October 2014 for placebo-controlled trials of pharmacological, behavioural, physical or alternative interventions for tics in children and young people with TS or CTD. Certainty in the evidence was assessed with the GRADE approach. Results: Forty trials were included [pharmacological (32), behavioural (5), physical (2), dietary (1)]. For tics/global score there was evidence favouring the intervention from four trials of a2-adrenergic receptor agonists [clonidine and guanfacine, standardised mean difference (SMD) = -0.71; 95% CI -1.03, -0.40; N = 164] and two trials of habit reversal training (HRT)/comprehensive behavioural intervention (CBIT) (SMD = -0.64; 95% CI -0.99, -0.29; N = 133). Certainty in the effect estimates was moderate. A post hoc analysis combining oral clonidine/guanfacine trials with a clonidine patch trial continued to demonstrate benefit (SMD = -0.54; 95% CI -0.92, -0.16), but statistical heterogeneity was high. Evidence from four trials suggested that antipsychotic drugs improved tic scores (SMD = -0.74; 95% CI -1.08, -0.40; N = 76), but certainty in the effect estimate was low. The evidence for other interventions was categorised as low or very low quality, or showed no conclusive benefit. Conclusions: When medication is considered appropriate for the treatment of tics, the balance of clinical benefits to harm favours a2-adrenergic receptor agonists (clonidine and guanfacine) as first-line agents. Antipsychotics are likely to be useful but carry the risk of harm and so should be reserved for when a2-adrenergic receptor agonists are either ineffective or poorly tolerated. There is evidence that HRT/CBIT is effective, but there is no evidence for HRT/CBIT alone relative to combining medication and HRT/CBIT. There is currently no evidence to suggest that the physical and dietary interventions reviewed are sufficiently effective and safe to be considered as treatments

    Which interventions offer best value for money in primary prevention of cardiovascular disease?

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    BackgroundDespite many decades of declining mortality rates in the Western world, cardiovascular disease remains the leading cause of death worldwide. In this research we evaluate the optimal mix of lifestyle, pharmaceutical and population-wide interventions for primary prevention of cardiovascular disease.Methods and FindingsIn a discrete time Markov model we simulate the ischaemic heart disease and stroke outcomes and cost impacts of intervention over the lifetime of all Australian men and women, aged 35 to 84 years, who have never experienced a heart disease or stroke event. Best value for money is achieved by mandating moderate limits on salt in the manufacture of bread, margarine and cereal. A combination of diuretic, calcium channel blocker, ACE inhibitor and low-cost statin, for everyone with at least 5% five-year risk of cardiovascular disease, is also cost-effective, but lifestyle interventions aiming to change risky dietary and exercise behaviours are extremely poor value for money and have little population health benefit.ConclusionsThere is huge potential for improving efficiency in cardiovascular disease prevention in Australia. A tougher approach from Government to mandating limits on salt in processed foods and reducing excessive statin prices, and a shift away from lifestyle counselling to more efficient absolute risk-based prescription of preventive drugs, could cut health care costs while improving population health.<br /
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