M Gillett

Bio: M Gillett is an academic researcher from University of Sheffield. The author has contributed to research in topics: Population & Quality-adjusted life year. The author has an hindex of 12, co-authored 20 publications receiving 1383 citations.

Screening for Type 2 Diabetes: Literature Review and Economic Modelling

Abstract: Objectives: To reconsider the aims of screening for undiagnosed diabetes, and whether screening should be for other abnormalities of glucose metabolism such as impaired glucose tolerance (IGT), or the ‘metabolic syndrome’. Also to update the previous review for the National Screening Committee (NSC) on screening for diabetes, including reviewing choice of screening test; to consider what measures would be taken if IGT and impaired fasting glucose (IFG) were identified by screening, and in particular to examine evidence on treatment to prevent progression to diabetes in these groups; to examine the cost-effectiveness of screening; and to consider groups at higher risk at which screening might be targeted. Data sources: Electronic databases were searched up to the end of June 2005. Review methods: Literature searches and review concentrated on evidence published since the last review of screening, both reviews and primary studies. The review of economic studies included only those models that covered screening. The new modelling extended an existing diabetes treatment model by developing a screening module. The NSC has a set of criteria, which it applies to new screening proposals. These criteria cover the condition, the screening test or tests, treatment and the screening programme. Screening for diabetes was considered using these criteria. Results: Detection of lesser degrees of glucose intolerance such as IGT is worthwhile, partly because the risk of cardiovascular disease (CVD) can be reduced by treatment aimed at reducing cholesterol level and blood pressure, and partly because some diabetes can be prevented. Several trials have shown that both lifestyle measures and pharmacological treatment can reduce the proportion of people with IGT who would otherwise develop diabetes. Screening could be two-stage, starting with the selection of people at higher risk. The second-stage choice of test for blood glucose remains a problem, as in the last review for NSC. The best test is the oral glucose tolerance test (OGTT), but it is the most expensive, is inconvenient and has weak reproducibility. Fasting plasma glucose would miss people with IGT. Glycatedhaemoglobin does not require fasting, and may be the best compromise. It may be that more people would be tested and diagnosed if the more convenient test was used, rather than the OGTT. Five economic studies assessed the costs and short-term outcomes of using different screening tests. None examined the long-term impact of different proportions of false negatives. All considered the costs that would be incurred and the numbers identified by different tests, or different cut-offs. Results differed depending on different assumptions. They did not give a clear guide as to which test would be the best in any UK screening programme, but all recognised that the choice of cut-off would be a compromise between sensitivity and specificity; there is no perfect test. The modelling exercise concluded that screening for diabetes appears to be cost-effective for the 40–70-year age band, more so for the older age bands, but even in the 40–49-year age group, the incremental cost-effectiveness ratio for screening versus no screening is only £10,216 per quality-adjusted life-year. Screening is more cost-effective for people in the hypertensive and obese subgroups and the costs of screening are offset in many groups by lower future treatment costs. The cost-effectiveness of screening is determined as much by, if not more than, assumptions about the degree of control of blood glucose and future treatment protocols than by assumptions relating to the screening programme. The very low cost now of statins is also an important factor. Although the prevalence of diabetes increases with age, the relative risk of CVD falls, reducing the benefits of screening. Screening for diabetes meets most of the NSC criteria, but probably fails on three: criterion 12, on optimisation of existing management of the condition; criterion 13, which requires that there should be evidence from high-quality randomised controlled trials (RCTs) showing that a screening programme would reduce mortality or morbidity; and criterion 18, that there should be adequate staffing and facilities for all aspects of the programme. It is uncertain whether criterion 19, that all other options, including prevention, should have been considered, is met. The issue here is whether all methods of improving lifestyles in order to reduce obesity and increase exercise have been sufficiently tried. The rise in overweight and obesity suggests that health promotion interventions have not so far been effective. Conclusions: The case for screening for undiagnosed diabetes is probably somewhat stronger than it was at the last review, because of the greater options for reduction of CVD, principally through the use of statins, and because of the rising prevalence of obesity and hence type 2 diabetes. However, there is also a good case for screening for IGT, with the aim of preventing some future diabetes and reducing CVD. Further research is needed into the duration of undiagnosed diabetes, and whether the rise in blood glucose levels is linear throughout or whether there may be a slower initial phase followed by an acceleration around the time of clinical diagnosis. This has implications for the interval after which screening would be repeated. Further research is also needed into the natural history of IGT, and in particular what determines progression to diabetes. An RCT of the type required by NSC criterion 13 is under way but will not report for about 7 years.

The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study.

Abstract: Background: Giant cell arteritis (GCA) is a relatively common form of primary systemic vasculitis, which, if left untreated, can lead to permanent sight loss. We compared ultrasound as an alternative diagnostic test with temporal artery biopsy, which may be negative in 9–61% of true cases. Objective: To compare the clinical effectiveness and cost-effectiveness of ultrasound with biopsy in diagnosing patients with suspected GCA. Design: Prospective multicentre cohort study. Setting: Secondary care. Participants: A total of 381 patients referred with newly suspected GCA. Main outcome measures: Sensitivity, specificity and cost-effectiveness of ultrasound compared with biopsy or ultrasound combined with biopsy for diagnosing GCA and interobserver reliability in interpreting scan or biopsy findings. Results: We developed and implemented an ultrasound training programme for diagnosing suspected GCA. We recruited 430 patients with suspected GCA. We analysed 381 patients who underwent both ultrasound and biopsy within 10 days of starting treatment for suspected GCA and who attended a follow-up assessment (median age 71.1 years; 72% female). The sensitivity of biopsy was 39% [95% confidence interval (CI) 33% to 46%], which was significantly lower than previously reported and inferior to ultrasound (54%, 95% CI 48% to 60%); the specificity of biopsy (100%, 95% CI 97% to 100%) was superior to ultrasound (81%, 95% CI 73% to 88%). If we scanned all suspected patients and performed biopsies only on negative cases, sensitivity increased to 65% and specificity was maintained at 81%, reducing the need for biopsies by 43%. Strategies combining clinical judgement (clinician’s assessment at 2 weeks) with the tests showed sensitivity and specificity of 91% and 81%, respectively, for biopsy and 93% and 77%, respectively, for ultrasound; cost-effectiveness (incremental net monetary benefit) was £485 per patient in favour of ultrasound with both cost savings and a small health gain. Inter-rater analysis revealed moderate agreement among sonographers (intraclass correlation coefficient 0.61, 95% CI 0.48 to 0.75), similar to pathologists (0.62, 95% CI 0.49 to 0.76). Limitations: There is no independent gold standard diagnosis for GCA. The reference diagnosis used to determine accuracy was based on classification criteria for GCA that include clinical features at presentation and biopsy results. Conclusion: We have demonstrated the feasibility of providing training in ultrasound for the diagnosis of GCA. Our results indicate better sensitivity but poorer specificity of ultrasound compared with biopsy and suggest some scope for reducing the role of biopsy. The moderate interobserver agreement for both ultrasound and biopsy indicates scope for improving assessment and reporting of test results and challenges the assumption that a positive biopsy always represents GCA. Future work: Further research should address the issue of an independent reference diagnosis, standards for interpreting and reporting test results and the evaluation of ultrasound training, and should also explore the acceptability of these new diagnostic strategies in GCA. Funding: he National Institute for Health Research Health Technology Assessment programme.

'Computer modeling of diabetes and its complications: A report on the Fourth Mount Hood Challenge Meeting'

Abstract: Computer simulation models are mathematical equations combined in a structured framework to represent some real or hypothetical system. One of their uses is to allow the projection of short-term data from clinical trials to evaluate clinical outcomes and costs over a long-term period. This technology is becoming increasingly important to assist decision making in modern medicine in situations where there is a paucity of long-term clinical trial data, as recently acknowledged in the American Diabetes Association Consensus Panel Guidelines for Computer Modeling of Diabetes and its Complications. The Mount Hood Challenge Meetings provide a forum for computer modelers of diabetes to discuss and compare models and identify key areas of future development to advance the field. The Fourth Mount Hood Challenge in 2004 was the first meeting of its kind to ask modelers to perform simulations of outcomes for patients in published clinical trials, allowing comparison against "real life" data. Eight modeling groups participated in the challenge. Each group was given three of the following challenges: to simulate a trial of type 2 diabetes (CARDS [Collaborative Atorvastatin Diabetes Study]); to simulate a trial of type 1 diabetes (DCCT [Diabetes Control and Complications Trial]); and to calculate outcomes for a hypothetical, precisely specified patient (cross-model validation). The results of the models varied from each other and for methodological reasons, in some cases, from the published trial data in important ways. This approach of performing systematic comparisons and validation exercises has enabled the identification of key differences among the models, as well as their possible causes and directions for improvement in the future. © 2007 by the American Diabetes Association.

Delivering the diabetes education and self management for ongoing and newly diagnosed (DESMOND) programme for people with newly diagnosed type 2 diabetes: cost effectiveness analysis

Abstract: Objectives To assess the long term clinical and cost effectiveness of the diabetes education and self management for ongoing and newly diagnosed (DESMOND) intervention compared with usual care in people with newly diagnosed type 2 diabetes. Design We undertook a cost-utility analysis that used data from a 12 month, multicentre, cluster randomised controlled trial and, using the Sheffield type 2 diabetes model, modelled long term outcomes in terms of use of therapies, incidence of complications, mortality, and associated effect on costs and health related quality of life. A further cost-utility analysis was also conducted using current “real world” costs of delivering the intervention estimated for a hypothetical primary care trust. Setting Primary care trusts in the United Kingdom. Participants Patients with newly diagnosed type 2 diabetes. Intervention A six hour structured group education programme delivered in the community by two professional healthcare educators. Main outcome measures Incremental costs and quality adjusted life years (QALYs) gained. Results On the basis of the data in the trial, the estimated mean incremental lifetime cost per person receiving the DESMOND intervention is £209 (95% confidence interval −£704 to £1137; €251, −€844 to €1363; $326, −$1098 to $1773), the incremental gain in QALYs per person is 0.0392 (−0.0813 to 0.1786), and the mean incremental cost per QALY is £5387. Using “real world” intervention costs, the lifetime incremental cost of the DESMOND intervention is £82 (−£831 to £1010) and the mean incremental cost per QALY gained is £2092. A probabilistic sensitivity analysis indicated that the likelihood that the DESMOND programme is cost effective at a threshold of £20 000 per QALY is 66% using trial based intervention costs and 70% using “real world” costs. Results from a one way sensitivity analysis suggest that the DESMOND intervention is cost effective even under more modest assumptions that include the effects of the intervention being lost after one year. Conclusion Our results suggest that the DESMOND intervention is likely to be cost effective compared with usual care, especially with respect to the real world cost of the intervention to primary care trusts, with reductions in weight and smoking being the main benefits delivered.

Non-Pharmacological Interventions to Reduce the Risk of Diabetes in People with Impaired Glucose Regulation: A Systematic Review and Economic Evaluation

Abstract: Background The prevalence of type 2 diabetes mellitus (T2DM) is increasing in the UK and worldwide. Before the onset of T2DM, there are two conditions characterised by blood glucose levels that are above normal but below the threshold for diabetes. If screening for T2DM in introduced, many people with impaired glucose tolerance (IGT) will be found and it is necessary to consider how they should be treated. The number would depend on what screening test was used and what cut-offs were chosen. Objective To review the clinical effectiveness and cost-effectiveness of non-pharmacological interventions, including diet and physical activity, for the prevention of T2DM in people with intermediate hyperglycaemia. Data sources Electronic databases, MEDLINE (1996–2011), EMBASE (1980–2011) and all sections of The Cochrane Library, were searched for systematic reviews, randomised controlled trials (RCTs) and other relevant literature on the effectiveness of diet and/or physical activity in preventing, or delaying, progression to T2DM.The databases were also searched for studies on the cost-effectiveness of interventions. Review methods The review of clinical effectiveness was based mainly on RCTs, which were critically appraised. Subjects were people with intermediate hyperglycaemia, mainly with IGT. Interventions could be diet alone, physical activity alone, or the combination. For cost-effectiveness analysis, we updated the Sheffield economic model of T2DM. Modelling based on RCTs may not reflect what happens in routine care so we created a ‘real-life’ modelling scenario wherein people would try lifestyle change but switch to metformin after 1 year if they failed. Results Nine RCTs compared lifestyle interventions (predominantly dietary and physical activity advice, with regular reinforcement and frequent follow-up) with standard care. The primary outcome was progression to diabetes. In most trials, progression was reduced, by over half in some trials. The best effects were seen in participants who adhered best to the lifestyle changes; a scenario of a trial of lifestyle change but a switch to metformin after 1 year in those who did not adhere sufficiently appeared to be the most cost-effective option. Limitations Participants in the RCTs were volunteers and their results may have been better than in general populations. Even among the volunteers, many did not adhere. Some studies were not long enough to show whether the interventions reduced cardiovascular mortality as well as diabetes. The main problem is that we know what people should do to reduce progression, but not how to persuade most to do it. Conclusion In people with IGT, dietary change to ensure weight loss, coupled with physical activity, is clinically effective and cost-effective in reducing progression to diabetes.

Periodontitis and diabetes: a two-way relationship

Abstract: Periodontitis is a common chronic inflammatory disease characterised by destruction of the supporting structures of the teeth (the periodontal ligament and alveolar bone). It is highly prevalent (severe periodontitis affects 10–15% of adults) and has multiple negative impacts on quality of life. Epidemiological data confirm that diabetes is a major risk factor for periodontitis; susceptibility to periodontitis is increased by approximately threefold in people with diabetes. There is a clear relationship between degree of hyperglycaemia and severity of periodontitis. The mechanisms that underpin the links between these two conditions are not completely understood, but involve aspects of immune functioning, neutrophil activity, and cytokine biology. There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. Incidences of macroalbuminuria and end-stage renal disease are increased twofold and threefold, respectively, in diabetic individuals who also have severe periodontitis compared to diabetic individuals without severe periodontitis. Furthermore, the risk of cardiorenal mortality (ischaemic heart disease and diabetic nephropathy combined) is three times higher in diabetic people with severe periodontitis than in diabetic people without severe periodontitis. Treatment of periodontitis is associated with HbA1c reductions of approximately 0.4%. Oral and periodontal health should be promoted as integral components of diabetes management.

Risk prediction models: II. External validation, model updating, and impact assessment

Abstract: Clinical prediction models are increasingly used to complement clinical reasoning and decision-making in modern medicine, in general, and in the cardiovascular domain, in particular. To these ends, developed models first and foremost need to provide accurate and (internally and externally) validated estimates of probabilities of specific health conditions or outcomes in the targeted individuals. Subsequently, the adoption of such models by professionals must guide their decision-making, and improve patient outcomes and the cost-effectiveness of care. In the first paper of this series of two companion papers, issues relating to prediction model development, their internal validation, and estimating the added value of a new (bio)marker to existing predictors were discussed. In this second paper, an overview is provided of the consecutive steps for the assessment of the model's predictive performance in new individuals (external validation studies), how to adjust or update existing models to local circumstances or with new predictors, and how to investigate the impact of the uptake of prediction models on clinical decision-making and patient outcomes (impact studies). Each step is illustrated with empirical examples from the cardiovascular field.

Beneficial health effects of modest weight loss.

Abstract: The medical effects of modest weight reduction (approximately 10% or less) in patients with obesity-associated medical complications were reviewed. The National Library of Medicine MEDLINE database and the Derwent RINGDOC database were searched to identify English language studies that examined the effects of weight loss in obese patients with serious medical complications commonly associated with obesity (non-insulin dependent diabetes mellitus (NIDDM or type II), hypertension, hyperlipidemia, hypercholesterolemia, and cardiovascular disease). Studies in which patients experienced approximately 10% or less weight reduction were selected for review. Studies indicated that, for obese patients with NIDDM, hypertension or hyperlipidemia, modest weight reduction appeared to improve glycemic control, reduce blood pressure, and reduce cholesterol levels, respectively. Modest weight reduction also appeared to increase longevity in obese individuals. In conclusion, a large proportion of obese individuals with NIDDM, hypertension, and hyperlipidemia experienced positive health benefits with modest weight loss. For patients who are unable to attain and maintain substantial weight reduction, modest weight loss should be recommended; even a small amount of weight loss appears to benefit a substantial subset of obese patients.

Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs.

Abstract: Diabet. Med. 29, 855–862 (2012) Abstract Aims To estimate the current and future economic burdens of Type 1 and Type 2 diabetes in the UK. Methods A top-down approach was used to estimate costs for 2010/2011 from aggregated data sets and literature. Prevalence and population data were used to project costs for 2035/2036. Direct health costs were estimated from data on diagnosis, lifestyle interventions, ongoing treatment and management, and complications. Indirect costs were estimated from data on mortality, sickness, presenteeism (potential loss of productivity among people who remain in work) and informal care. Results Diabetes cost approximately £23.7bn in the UK in 2010/2011: £9.8bn in direct costs (£1bn for Type 1 diabetes and £8.8bn for Type 2 diabetes) and £13.9bn in indirect costs (£0.9bn and £13bn). In real terms, the 2035/2036 cost is estimated at £39.8bn: £16.9bn in direct costs (£1.8bn for Type 1 diabetes and £15.1bn for Type 2 diabetes) and £22.9bn in indirect costs (£2.4bn and £20.5bn). Sensitivity analysis applied to the direct costs produced a range of costs: between £7.9bn and £11.7bn in 2010/2011 and between £13.8bn and £20bn in 2035/2036. Diabetes currently accounts for approximately 10% of the total health resource expenditure and is projected to account for around 17% in 2035/2036. Conclusions Type 1 and Type 2 diabetes are prominent diseases in the UK and are a significant economic burden. Data differentiating between the costs of Type 1 and Type 2 diabetes are sparse. Complications related to the diseases account for a substantial proportion of the direct health costs. As prevalence increases, the cost of treating complications will grow if current care regimes are maintained.

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice.

Abstract: To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV.