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J Hutton

Publications and source records attributed to J Hutton.

At least 19 recordsLinked to original sources
PubMed2006

Initial results of screening of nondiabetic organ donors for expression of islet autoantibodies.

CONTEXT: Type 1A diabetes is characterized by a long prodromal phase during which autoantibodies to islet antigens are present. Nevertheless, we lack data on the pancreatic pathology of subjects who are positive for islet autoantibodies (to islet autoantigens GAD65, insulin, and ICA512). OBJECTIVE: In this manuscript, we describe a novel strategy in obtaining pancreata and pancreatic lymph nodes from islet autoantibody-positive organ donors that involves careful coordination among the laboratory and the organ donor provider organization. DESIGN: We developed a rapid screening protocol for islet autoantibodies measurement of organ donors to allow identification of positive subjects before organ harvesting. In this way we were able to obtain pancreata and pancreatic lymph nodes from subjects with and without islet autoimmunity. SETTING: The organ donors used in this study were obtained from the general community. SUBJECTS: The population studied consisted of 112 organ donors (age range 1 month to 86 yr, mean age 39 yr). MAIN OUTCOME MEASURE: The main outcome measure of this study consisted of evaluating the pancreatic histology and identify T cells autoreactive for islet antigens in the pancreatic lymph nodes. RESULTS: To date we have identified three positive subjects and obtained the pancreas for histological evaluation from one of the autoantibody-positive donors who expressed ICA512 autoantibodies. Although this subject did not exhibit insulitis, lymphocytes derived from pancreatic lymph nodes reacted to the islet antigen phogrin. CONCLUSION: In summary, these results indicate that it is possible to screen organ donors in real time for antiislet antibodies, characterize pancreatic histology, and obtain viable T cells for immunological studies.

Adolescent↗
PubMed2005

Cost-effectiveness of oral ibandronate compared with intravenous (i.v.) zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy.

BACKGROUND: Ibandronate is the first third-generation bisphosphonate to have both oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate in female breast cancer patients with metastatic bone disease, undergoing i.v. chemotherapy. METHODS: A global economic model was adapted to the UK National Health Service (NHS), with primary outcomes of direct healthcare costs and quality-adjusted life years (QALYs). Efficacy, measured as relative risk reduction of skeletal-related events (SREs), was obtained from clinical trials. Resource use data for i.v. bisphosphonates and the cost of managing SREs were obtained from published studies. Hospital management and SRE treatment costs were taken from unit cost databases. Monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with/without an SRE to adjust survival for quality of life. Model design and inputs were validated through expert UK clinician review. RESULTS: Total cost, including drug acquisition, was pound 386 less per patient with oral ibandronate vs. i.v. zoledronic acid and pound 224 less vs. i.v. generic pamidronate. Oral ibandronate gained 0.019 and 0.02 QALYs vs. i.v. zoledronic acid and i.v. pamidronate, respectively, making it the economically dominant option. At a threshold of pound 30,000 per QALY, oral ibandronate was cost-effective vs. zoledronic acid in 85% of simulations and vs. pamidronate in 79%. CONCLUSIONS: Oral ibandronate is a cost-effective treatment for metastatic bone disease from breast cancer due to reduced SREs, bone pain, and cost savings from avoidance of resource use commonly associated with bisphosphonate infusions.

Administration, Oral↗
PubMed2005

Cost effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in the United Kingdom.

Drotrecogin alfa (activated) is licensed in Europe for the treatment of severe sepsis in patients with multiple organ failure. We constructed a model to assess the cost effectiveness of drotrecogin alfa (activated) from the perspective of the UK National Health Service when used in adult intensive care units. Patient outcomes from a 28-day international clinical trial (PROWESS) and a subsequent follow-up study (EVBI) were supplemented with UK data. Cost effectiveness was assessed as incremental cost per life year and per quality adjusted life year saved compared to placebo alongside best usual care. Applying the 28-day mortality outcomes of the PROWESS study, the model produced a cost per life year saved of 4608 UK pounds and cost per quality adjusted life year saved of 6679 UK pounds. Equivalent results using actual hospital outcomes were 7625 UK pounds per life year and 11,051 UK pounds per quality adjusted life year. Drotrecogin alfa (activated) appears cost effective in treating severe sepsis in UK intensive care units.

Adult↗
PubMed2004

One year comparison of costs of coronary surgery versus percutaneous coronary intervention in the stent or surgery trial.

OBJECTIVES: To compare initial and one year costs of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in the stent or surgery trial. DESIGN: Prospective, unblinded, randomised trial. SETTING: Multicentre study. PATIENTS: 988 patients with multivessel disease. INTERVENTIONS: CABG and stent assisted PCI. MAIN OUTCOME MEASURES: Initial hospitalisation and one year follow up costs. RESULTS: At one year mortality was 2.5% in the PCI arm and 0.8% in the CABG arm (p = 0.05). There was no difference in the composite of death or Q wave myocardial infarction (6.9% for PCI v 8.1% for CABG, p = 0.49). There were more repeat revascularisations with PCI (17.2% v 4.2% for CABG). There was no significant difference in utility between arms at six months or at one year. Quality adjusted life years were similar 0.6938 for PCI v 0.6954 for PCI, Delta = 0.00154, 95% confidence interval (CI) -0.0242 to 0.0273). Initial length of stay was longer with CABG (12.2 v 5.4 days with PCI, p < 0.0001) and initial hospitalisation costs were higher (7321 pounds sterling v 3884 pounds sterling for PCI, Delta = 3437 pounds sterling, 95% CI 3040 pounds sterling to 3848 pounds sterling). At one year the cost difference narrowed but costs remained higher for CABG (8905 pounds sterling v 6296 pounds sterling for PCI, Delta = 2609 pounds sterling, 95% CI 1769 pounds sterling to 3314 pounds sterling). CONCLUSIONS: Over one year, CABG was more expensive and offered greater survival than PCI but little added benefit in terms of quality adjusted life years. The additional cost of CABG can be justified only if it offers continuing benefit at no further increase in cost relative to PCI over several years.

Angioplasty, Balloon, Coronary↗
PubMed2004

Folic acid supplements to prevent neural tube defects: trends in East of Ireland 1996-2002.

Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for ten years in Ireland, without a concomitant reduction in the total birth prevalence of NTD. The effectiveness of folic acid promotion as the sole means of primary prevention of NTD is therefore questionable. We examined trends in folic acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing the value of this approach. From 1996-2002, 300 women attending ante-natal clinics in Dublin hospitals annually were surveyed regarding their knowledge and use of folic acid. During the period the proportion who had heard of folic acid rose from 54% to 94% between 1996 and 2002 (c2 test for trend: p<0.001). Knowledge that folic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: p<0.001). Although the proportion who took folic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: p<0.001), peri-conceptional intake did not rise above 24% in any year. There is a high awareness of folic acid and its relation to NTD, which is not matched by peri-conceptional uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy planning. To date promotional campaigns appear to have been ineffective in reducing the prevalence of NTD in Ireland. Consequently, fortification of staple foodstuffs is the only practical and reliable means of primary prevention of NTD.

Adult↗
PubMed2003

A Markov model of treatment of newly diagnosed epilepsy in the UK. An initial assessment of cost-effectiveness of topiramate.

Long-term comparative trials among newer antiepileptic drugs are lacking; therefore decision models are needed to guide treatment decisions. The goal of this study was to develop an economic model of newly diagnosed epilepsy in the UK and to provide the first assessment of topiramate. A Markov model was developed combining data from clinical trials, cost-of illness, mortality, and utility studies. Expected costs and utilities associated with treatment strategies (first- and second-line treatments) were compared to find the cost-effectiveness frontier. First- and second-line monotherapy with topiramate or carbamazepine in partial seizures was less costly and more effective than other scenarios. In generalised seizures first-line topiramate was cost-effective with valproate or lamotrigine as second-line treatments depending on the set of utilities used. Models provide a relevant framework within which costs and health gains of antiepileptic drugs treatment options can be studied. Our findings are further evidence of the promising role of topiramate for patients with newly diagnosed epilepsy.

Journal Article↗
PubMed2003

Changes in cost-effectiveness over time. The case of Epoetin Alfa for renal replacement therapy patients in the UK.

We analysed the factors influencing cost-effectiveness of a health care intervention over time using economic evaluations of erythropoietin as a case study. The analytical framework of a study conducted in 1990 was used to revisit the cost-effectiveness of erythropoietin. Study variables were updated to 2000 using meta-analysis, published sources, and expert opinion. After 10 years of further experience with the use of erythropoietin the cost-effectiveness ratio now falls within the range considered acceptable in the UK. The analysis shows that the vast proportion of the reduction in the cost-effectiveness ratio achieved since 1990 results from reductions in the dose and price of erythropoietin. True cost-effectiveness of a treatment can change over time, and early analysis can reach incorrect conclusions because of data deficiencies. The existence of a body such as NICE might have delayed the widespread adoption of erythropoietin in the UK, but the higher standards of clinical and economic evidence demanded by such a body might have expedited the appropriate pricing,dosage, and hence utilisation of the treatment.

Journal Article↗
PubMed2002

Cost effectiveness of eptifibatide in acute coronary syndromes; an economic analysis of Western European patients enrolled in the PURSUIT trial. The Platelet IIa/IIb in unstable Angina: Receptor Suppression Using Integrilin Therapy.

AIMS: To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infarction without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial. METHODS AND RESULTS: Health care resources were collected for the Western European PURSUIT trial patients (n=3697). Unit costs for major resources were developed within six countries using a consistent bottom-up methodology. Resource consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial. Eptifibatide was estimated to cost 524 Euros per treatment. Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios. Additionally, cost per death and non-fatal myocardial infarction at 30 days was calculated. Sensitivity analyses were conducted on the discount rate and resource consumption. Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3% discount. Using resource consumption based on countries with low coronary arteriography rates, the cost per year of life saved was between 3329 Euros and 10 079 Euros. Using resource consumption based on high coronary arteriography rate countries, the cost per year of life saved was between 17 089 Euros and 24 099 Euros. Assuming no difference in treatment costs except for the addition of eptifibatide, the incremental cost per year of life saved was 23 818 Euros. CONCLUSIONS: Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infarction at 30 days, which was sustained at 6 months. Long-term projections indicate a modest increase in survival in eptifibatide patients. These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use.

Acute Disease↗
PubMed2001

A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma.

BACKGROUND: Endoscopic ultrasound (EUS) may be used for preoperative staging of gastro-oesophageal carcinoma but performance values given in the literature differ. AIMS: To identify and synthesise findings from all articles on the performance of EUS in tumour, node, metastasis (TNM) staging of gastro-oesophageal carcinoma. SOURCE: Published and unpublished English language literature, 1981-1996. METHODS: Data on the staging performance of EUS were retrieved and evaluated. Summary receiver operator characteristic methodology was used for synthesis, and a summary estimate of performance, Q*, obtained. Multiple regression analysis was used to assess study validity and investigate reasons for differences in performance. RESULTS: Twenty seven primary articles were assessed in detail. Thirteen supplied results for staging oesophageal cancer, 13 for gastric cancer, and four for cancers at the gastro-oesophageal junction. For gastric T staging, Q*=0.93 (95% confidence interval (CI) 0.91-0.95) and for oesophageal T staging, Q*=0.89 (95% CI 0.88-0.92). For gastro-oesophageal T staging, including cancers at the gastro-oesophageal junction, Q*=0.91 (95% CI 0.89-0.93). Inclusion of cases with non-traversable stenosis was found to slightly reduce staging performance. For N staging, Q*=0.79 (95% CI 0.75-0.83). In articles that compared EUS directly with incremental computed tomography, EUS performed better. None of the variables assessed in the regression analysis was significant using a Bonferroni correction. Three variables (anatomical location, traversability, and blinding) showed strong relationships for future research and validation. CONCLUSIONS: EUS is highly effective for discrimination of stages T1 and T2 from stages T3 and T4 for primary gastro-oesophageal carcinomas. The failure rate of EUS from non-traversability of a stenotic cancer may be a limitation in some patient groups.

Confidence Intervals↗
PubMed2001

Treatment pathways, resource use and costs in the management of small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) represents about 20% of primary lung tumours and the costs associated with the management of SCLC can be significant. The main objective of this study was to obtain information on current patterns of care and associated resource use and costs for patients with SCLC from initial diagnosis and treatment phase, throughout disease progression and terminal care. METHODS: A 4 year retrospective patient chart analysis (1994-7) was conducted on a consecutive series of 109 patients diagnosed with SCLC in two Newcastle hospitals. For this consecutive series of patients all details about care received including tests and procedures, treatment, and medication from diagnosis till death were recorded. Pathways of care and forms were designed to enable resource use to be captured for different disease phases. Unit costs were determined from a variety of sources including the Newcastle Hospitals NHS Trust Finance Department and the British National Formulary. RESULTS: The average total cost per patient calculated for the full cohort of 109 patients was pound 11,556. Initial treatment was the most resource use intensive constituting 48.2% of the total cost. The major cost element throughout all disease phases was hospitalisation. Twenty eight percent of the total costs of care occur after recurrence of the disease until death, of which 73% are generated by terminal care. CONCLUSION: The results of this retrospective medical chart analysis show that the costs of care of SCLC are considerable, although the variability between patients in terms of the type and quantity of resource use is very high. Analyses such as this provide a useful insight into resources used in actual clinical practice.

Aged↗
PubMed2001

A comparison of the costs and survival of hospital-admitted stroke patients across Europe.

BACKGROUND AND PURPOSE: Policy makers require evidence on the costs and outcomes of different ways of organizing stroke care. This study compared the costs and survival of different ways of providing stroke care. METHODS: Hospitalized stroke patients from 13 European centers were included, with demographic, case-mix, and resource use variables measured for each patient. Unit costs were collected and converted into US dollars using the purchasing power parity (PPP) index. Cox and linear regression analyses were used to compare survival and costs between the centers adjusting for case mix. RESULTS: A total of 1847 patients were included in the study. After case-mix adjustment, the mean predicted costs ranged from $466 [95% CI 181 to 751] in Riga (Latvia) to $8512 [7696 to 9328] in Copenhagen (Denmark), which reflected differences in unit costs, and resource use. The mean length of hospitalization ranged from 8.3 days in Menorca (Spain) to 36.8 days in Turku B (Finland). In the 3 Finnish centers at least 80% of patients were admitted to wards providing organized stroke care, which was not provided at the centers in Almada (Portugal), Menorca, or Riga. Patients in Turku A and Turku B were less likely to die than those in Riga, Warsaw (Poland), or Menorca. The adjusted hazard ratios were 0.18 [0.10 to 0.32] for Turku A, 0.18 [0.10 to 0.32] for Turku B, 0.68 [0.48 to 0.96] for Warsaw, and 0.56 [0.33 to 0.96] for Menorca, all compared with Riga. CONCLUSIONS: The cost of stroke care varies across Europe because of differences in unit costs, and resource use. Further research is needed to assess which ways of organizing stroke care are the most cost-effective.

Aged↗
PubMed2001

Developing guidance for budget impact analysis.

The role of economic evaluation in the efficient allocation of healthcare resources has been widely debated. Whilst economic evidence is undoubtedly useful to purchasers, it does not address the issue of affordability which is an increasing concern. Healthcare purchasers are concerned not just with maximising efficiency but also with the more simplistic goal of remaining within their annual budgets. These two objectives are not necessarily consistent. This paper examines the issue of affordability, the relationship between affordability and efficiency and builds the case for why there is a growing need for budget impact models to complement economic evaluation. Guidance currently available for such models is also examined and it is concluded that this guidance is currently insufficient. Some of these insufficiencies are addressed and some thoughts on what constitutes best practice in budget impact modelling are suggested. These suggestions include consideration of transparency, clarity of perspective, reliability of data sources, the relationship between intermediate and final end-points and rates of adoption of new therapies. They also include the impact of intervention by population subgroups or indications, reporting of results, probability of re-deploying resources, the time horizon, exploring uncertainty and sensitivity analysis, and decision-maker access to the model. Due to the nature of budget impact models, the paper does not deliver stringent methodological guidance on modelling. The intention was to provide some suggestions of best practice in addition to some foundations upon which future research can build.

Budgets↗
PubMed2001

Cost effectiveness of treatment options in advanced breast cancer in the UK.

OBJECTIVE: To compare clinical and economic study data for docetaxel, paclitaxel and vinorelbine in the treatment of anthracycline-resistant advanced breast cancer. STUDY DESIGN AND METHODS: A Markov decision-analysis model to simulate the clinical course of a 'typical' patient with advanced breast cancer during salvage chemotherapy was updated with response rates and adverse effect rates from phase III clinical trial data for docetaxel, paclitaxel and vinorelbine. Costs were taken from UK national databases and hospitals. Utilities were estimated from 30 oncology nurses in the UK using the standard gamble method. PERSPECTIVE: National Health Service. RESULTS: When compared with other chemotherapeutic agents, docetaxel has been shown to increase response rate, time to progression and survival in patients with advanced breast cancer. In the base-case analysis, the incremental cost-utility ratio for docetaxel versus paclitaxel was pound1995 per quality-adjusted life year (QALY) gained (1998 values). The incremental cost-utility ratio for docetaxel versus vinorelbine was pound14 055 per QALY gained. In the comparison with vinorelbine, docetaxel provided the equivalent of an additional 92 days of perfect health. Sensitivity analyses confirmed the robustness of the model and the validity of the base-case analysis results. Even in the worst case scenarios, docetaxel remained cost effective compared with paclitaxel and vinorelbine. CONCLUSIONS: These findings support the use of the taxoids, notably docetaxel, in the management of advanced breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes autoantigen.

Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells in genetically susceptible individuals. Growing evidence suggests that genetically determined variation in the expression of self-antigens in thymus may affect the shaping of the T-cell repertoire and susceptibility to autoimmunity. For example, both allelic variation and parent-of-origin effects influence the thymic expression of insulin (a known type 1 diabetes autoantigen), and insulin gene transcription levels in thymus inversely correlate with susceptibility in both humans and transgenic models. It is unclear why patients lose tolerance to IA-2 (insulinoma-associated tyrosine phosphatase-like protein, or islet cell antigen 512 [ICA512]), especially because IA-2 polymorphisms are not associated with type 1 diabetes. We report that alternative splicing determines differential IA-2 expression in islets compared with thymus and spleen. Islets express full-length mRNA and two alternatively spliced transcripts, whereas thymus and spleen exclusively express an alternatively spliced transcript lacking exon 13. This encodes for the transmembrane (TM) and juxta-membrane (JM) domains that comprise several type 1 diabetes target epitopes, supporting the concept that tolerance to IA-2 epitopes not expressed in lymphoid organs may not be achieved. We propose differential splicing as a regulatory mechanism of gene expression playing a permissive role in the development of autoimmune responses to IA-2. Our findings also show that candidate gene expression studies can help in dissecting the complex genetic determinants of a multifactorial disease such as type 1 diabetes.

Adult↗
PubMed2000

Identifying studies for systematic reviews. An example from medical imaging.

OBJECTIVES: To determine if published figures on the proportion of articles included in systematic reviews and identified in electronic databases are applicable to an example from medical imaging. METHODS: A systematic review was performed. Additionally, sensitivity and precision of a MEDLINE search were compared with values from three published searches, each customized for a specific field. RESULTS: All articles included in the systematic review were in electronic databases. The MEDLINE search had low precision compared with searches in other fields. CONCLUSIONS: In a specific area of medical imaging, electronic databases, including MEDLINE, are reliable sources of articles.

Bibliometrics↗