Liraglutide for the treatment of type 2 diabetes : a single technology appraisal

This paper presents a summary of the Evidence Review Group (ERG) report into the clinical effectiveness and cost-effectiveness of liraglutide in the treatment of type 2 diabetes mellitus, based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer proposed the use of liraglutide as a second or third drug in patients with type 2 diabetes whose glycaemic control was unsatisfactory with metformin, with or without a second oral glucoselowering drug. The submission included six manufacturer-sponsored trials that compared the efficacy of liraglutide against other glucose-lowering agents. Not all of the trials were relevant to the decision problem. The most relevant were Liraglutide Effects and Actions in Diabetes 5 (LEAD-5) (liraglutide used as part of triple therapy and compared against insulin glargine) and LEAD-6 [liraglutide in triple therapy compared against another glucagon like peptide-1 (GLP-1) agonist, exenatide]. Five of the six trials were published in full and one was then unpublished. Two doses of liraglutide, 1.2 and 1.8 mg, were used in some trials but in the two comparisons in triple therapy, against glargine and exenatide, only the 1.8-mg dose was used. Liraglutide in both doses was found to be clinically effective in lowering blood glucose concentration [glycated haemoglobin (HbA1c)], reducing weight (unlike other glucose-lowering agents, such as sulphonylureas, glitazones and insulins, which cause weight gain) and also reducing systolic blood pressure (SBP). Hypoglycaemia was uncommon. The ERG carried out meta-analyses comparing the 1.2- and 1.8-mg doses of liraglutide, which suggested that there was no difference in control of diabetes, and only a slight difference in weight loss, insufficient to justify the extra cost

Evidence review : liraglutide for the treatment of type 2 diabetes

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of liraglutide in the treatment of type 2 diabetes mellitus, based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The manufacturer proposed the use of liraglutide as a second or third drug in patients with type 2 diabetes whose glycaemic control was unsatisfactory with metformin, with or without a second oral glucose-lowering drug. The submission included six manufacturer-sponsored trials that compared the efficacy of liraglutide against other glucose-lowering agents. Not all of the trials were relevant to the decision problem. The most relevant were Liraglutide Effects and Actions in Diabetes 5 (LEAD-5) (liraglutide used as part of triple therapy and compared against insulin glargine) and LEAD-6 [liraglutide in triple therapy compared against another glucagon-like peptide-1 agonist, exenatide]. Five of the six trials were published in full and one was then unpublished. Two doses of liraglutide, 1.2 and 1.8 mg, were used in some trials, but in the two comparisons in triple therapy, against glargine and exenatide, only the 1.8-mg dose was used. Liraglutide in both doses was found to be clinically effective in lowering blood glucose concentration [glycated haemoglobin (HbA1c)], reducing weight (unlike other glucose-lowering agents, such as sulphonylureas, glitazones and insulins, which cause weight gain) and also reducing systolic blood pressure (SBP). Hypoglycaemia was uncommon. The ERG carried out meta-analyses comparing the 1.2- and 1.8-mg doses of liraglutide, which suggested that there was no difference in control of diabetes, and only a slight difference in weight loss, insufficient to justify the extra cost. The cost-effectiveness analysis was carried out using the Center for Outcomes Research model. The health benefit was reported as quality-adjusted life-years (QALYs). The manufacturer estimated the cost-effectiveness to be £15,130 per QALY for liraglutide 1.8 mg compared with glargine, £10,054 per QALY for liraglutide 1.8 mg compared with exenatide, £10,465 per QALY for liraglutide 1.8 mg compared with sitagliptin, and £9851 per QALY for liraglutide 1.2 mg compared with sitagliptin. The ERG conducted additional sensitivity analyses and concluded that the factors that carried most weight were: in the comparison with glargine, the direct utility effects of body mass index (BMI) changes and SBP, with some additional contribution from HbA1c in the comparison with exenatide, HbA1c, with some additional effects from cholesterol and triglycerides in the comparison with sitagliptin, HbA1c and direct utility effects of BMI changes. The European Medicines Agency has approved liraglutide in dual therapy with other oral glucose-lowering agents. NICE guidance recommends the use of liraglutide 1.2 mg in triple therapy when glycaemic control remains or becomes inadequate with a combination of two oral glucose-lowering drugs. The use of liraglutide 1.2 mg in a dual therapy is indicated only in patients who are intolerant of, or have contraindications to, three oral glucose-lowering drugs. The use of liraglutide 1.8 mg was not approved by NICE. The ERG recommends research into the (currently unlicensed) use of liraglutide in combination with long-acting insulin

Acessibilidade e utilização dos espaços verdes urbanos nas cidades de Coimbra (Portugal) e Salamanca (Espanha)

ACCESSIBILITY AND USE OF URBAN GREEN SPACES IN THE CITIES OF COIMBRA (PORTUGAL) AND SALAMANCA (SPAIN). In a society that values more and more wellbeing, health and free time, the introduction of urban green spaces (UGS) next to residential areas has become a citizen’s right and requirement. This paper analyses the distribution and accessibility of UGS in the cities of Coimbra and Salamanca and evaluates their influence on the needs of the resident populations, in terms of users’ age, frequency of usage, as well as of motivation and ways to enjoy the facilities. In Coimbra there is a concentration of UGS, whereas in Salamanca there is a dispersion of such spaces, which has resulted in the different usage that people make of them. In fact, although Coimbra offers more urban green space (per inhabitant), their usage is reduced as people go there mainly by car, contrary to what happens in Salamanca. Consequently, Coimbra’s inhabitants choose these green spaces because of the activities they can be used for, whereas Salamanca’s inhabitants choose them for their proximity

Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction : systematic review and economic evaluation

Background The blockage of a coronary artery (coronary thrombosis) can lead to a heart attack (acute myocardial infarction). There are several ways of trying to overcome this blockage. The methods include drug treatment to dissolve the clot (thrombolysis) and physical intervention, either by passing a catheter into the affected artery [angioplasty or percutaneous coronary intervention (PCI)], or bypassing the blocked section by cardiac surgery [coronary artery bypass grafting (CABG)]. Thrombolysis can be given in the community before the patient is sent to hospital, or delayed until after admission. Prehospital thrombolysis is not common in the UK. Immediate angioplasty is not routinely available in the UK at present; it is much more common in the USA. Objectives To review the clinical evidence comparing immediate angioplasty with thrombolysis, and to consider whether it would be cost-effective. Methods This report was based on a systematic review of the evidence of clinical effectiveness and an economic analysis of cost-effectiveness based on the clinical review and on cost data from published sources and de novo data collection. Data sources The search strategy searched six electronic databases (including Medline, Cochrane Library and EMBASE), with English-language limits, for the periods up to December 2002. Bibliographies of related papers were assessed for relevant studies and experts contacted for advice and peer review, and to identify additional published and unpublished references. Study selection For clinical effectiveness, a comprehensive review of randomised controlled trials (RCTs) was used for efficacy, and a selection of observational studies such as case series or audit data for effectiveness safety in routine practice. RCTs of thrombolysis were used to assess the relative value of prehospital and hospital thrombolysis. Observational studies were used to assess the representativeness of patients in the RCTs, and to determine whether different groups have different capacity to benefit. They were used to assess the implications of wider diffusion of the technology away from major centres. Data extraction Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of systematic reviews, RCTs, controlled clinical trials and economic studies was assessed using criteria recommended by the NHS Centre for Reviews and Dissemination (University of York). Study synthesis Clinical effectiveness was synthesised through a narrative review with full tabulation of results of all included studies and a meta-analysis to provide a precise estimate of absolute clinical benefit. Consideration was given to the effect of the growing use of stents. The economic modelling adopted an NHS perspective to develop a decision-analytical model of cost-effectiveness focusing on opportunity costs over the short term (6 months). Results and conclusion Number and quality of studies, and summary of benefits There were several good-quality systematic reviews, including a Cochrane review, as well as an individual patient meta-analysis and a number of recent trials not included in the reviews. The results were consistent in showing an advantage of immediate angioplasty over hospital thrombolysis. The updated meta-analysis showed that mortality is reduced by about one-third, from 7.6% to 4.9% in the first 6 months, and by about the same in studies of up to 24 months. Reinfarction is reduced by over half, from 7.6% to 3.1%. Stroke is reduced by about two-thirds, from 2.3% with thrombolysis to 0.7% with PCI, with the difference being due to haemorrhagic stroke. The need for CABG is reduced by about one-third, from 13.2% to 8.4%. Caution is needed in interpreting the older trials, as changes such as an increase in stenting and the use of the glycoprotein IIb/IIa inhibitors may improve the results of PCI. There is little evidence comparing prehospital thrombolysis with immediate PCI. One good quality study from France showed that prehospital thrombolysis with PCI in those in whom thrombolysis failed was as good as universal PCI. Research on thrombolysis followed by PCI, known as facilitated PCI, is underway, but results are not yet available. Further caveats are needed. Trials may be done in select centres and results may not be as good in lower volume centres, or out of normal working hours. In addition, much of the marginal mortality benefit of PCI over hospital thrombolysis may be lost if door-to-balloon time were more than 1 hour longer than door-to-needle time. Conversely, within the initial 6 hours, the later patients present, the greater the relative advantage of PCI. Cost-effectiveness If both interventions were routinely available, the economic analysis favours PCI, given the assumptions of the model. Results suggest that PCI is more cost-effective than thrombolysis, providing additional benefits in health status at some extra cost and an incremental cost per unit change in health status under the £30,000 threshold in most instances. In the longer term, the cost difference is expected to be reduced because of higher recurrence and reintervention rates among those who had thrombolysis. The model is not particularly sensitive to variations in probabilities from the clinical effectiveness analysis. However, very few units in England could offer a routine immediate PCI service at present, and there would be considerable resource implications of setting up such services. Without a detailed survey of existing provision, it is not possible to quantify the implications, but they include both capital and revenue: an increase in catheter laboratory provision and running costs. The greatest problem would be staffing, and that would take some years to resolve. A gradual incrementalist approach based on clinical networks, with transfer to centres able to offer PCI, could be used. In rural areas, one option could be to promote an increase in prehospital thrombolysis, with PCI for thrombolysis failures. Need for further research There is a need for economic data on the long-term consequences of the treatment, the quality of life of patients after treatment and the effects of PCI following thrombolysis failure

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Self-monitoring of blood glucose in type 2 diabetes : systematic review

The evidence suggested that SMBG is of limited clinical effectiveness in improving glycaemic control in people with T2DM on oral agents, or diet alone, and is therefore unlikely to be cost-effective. SMBG may lead to improved glycaemic control only in the context of appropriate education - both for patients and health-care professionals - on how to respond to the data, in terms of lifestyle and treatment adjustment. Also, SMBG may be more effective if patients are able to self-adjust drug treatment. Further research is required on the type of education and feedback that are most helpful, characteristics of patients benefiting most from SMBG, optimal timing and frequency of SMBG, and the circumstances under which SMBG causes anxiety and/or depression

Screening for hyperglycaemia in pregnancy : a rapid update for the National Screening Committee

Background Screening for gestational diabetes has long been a controversial topic. A previous Health Technology Assessment (HTA) report reviewed literature on screening for gestational diabetes mellitus (GDM) and assessed the case for screening against the criteria set by the National Screening Committee. Objective To update a previous HTA report which reviewed the literature on screening for GDM by examining evidence that has emerged since that last report, including the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS), the Maternal and Fetal Medicine Units Network (MFMUN) trial and the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. To review data on recent trends in maternal age at birth and on the prevalence of overweight and obesity and the effect on prevalence of GDM. Data sources A systematic review and meta-analysis of the literature was carried out. The bibliographic databases used were MEDLINE (1996 to January 2009), EMBASE (1996 to December 2009), the Cochrane Library 2008 issue 4, the Centre for Reviews and Dissemination database and the Web of Science. Review methods For the review of treatment with oral drugs versus insulin, a full systematic review and meta-analysis was carried out. The results of the ACHOIS, MFMUN and HAPO studies were summarised and their implications discussed. Findings of a selection of other recent studies, relevant to the continuum issue, were summarised. Some recent screening studies were reviewed, including a particular focus on studies of screening earlier in pregnancy. Results The HAPO results showed a linear relationship between plasma glucose and adverse outcomes – there is a continuum of risk with no clear threshold which could divide women into those with gestational diabetes and those without. There was good evidence from trials and the meta-analysis that women who fail to control hyperglycaemic in pregnancy on lifestyle measures alone can be safely and effectively be treated with oral agents, metformin or glibenclamide, rather than going directly to insulin. Evidence showed few differences in results between glibenclamide and insulin and metformin and insulin. The exceptions were that there was less maternal hypoglycaemia with glibenclamide, but less neonatal hypoglycaemia and lower birthweight with insulin, and there was less maternal weight gain with metformin. The ACHOIS and MFMUN trials showed reductions in perinatal complications among infants born to mothers who were provided with more intensive dietary advice, blood glucose monitoring and insulin when required. The HAPO study demonstrated adverse outcomes over a much wider range of blood glucose (BG) than the traditional definition of GDM. In the HAPO study, no one measure of BG came out as being clearly the best, although fasting plasma glucose (FPG) was as good as any, and had advantages of being more convenient than an oral glucose tolerance test (OGTT), but correlations between fasting and post-load levels were quite poor. Two screening strategies dominated; (1) selection by the American Diabetes Association criteria followed by the 75-g OGTT [incremental cost-effectiveness ratio (ICER) £3678], and (2) selection by high-risk ethnicity followed by the 75-g OGTT (ICER £21,739). Studies indicated that costs are about £1833 higher for pregnancies complicated by gestational diabetes, suggesting that prevention would be worthwhile. Limitations Not all of the HAPO results have been published, and none of the reviewed economic studies resolved the most difficult issue – at what level of BG does intervention become cost-effective? Conclusions The evidence base has improved since the last HTA review in 2002. There is now good evidence for treatment of oral drugs instead of insulin and it looks increasingly as if FPG could be the test of choice. However some key uncertainties remain to be resolved, which can be done by further analysis of the already collected HAPO data and by using the UK model used in developing the NICE guidelines to assess the cost-effectiveness of intervention in each of the seven HAPO categories

Analyse der Lebensqualität von Patienten mit Osteoidosteom vor und nach Behandlung mittels Radiofrequenzablation

Hintergrund: Ziel dieser Arbeit ist es, die Effektivität der Behandlung von Osteoidosteomen (OO) mittels Radiofrequenzablation (RFA) zu untersuchen. Dabei wird insbesondere die Rezidivrate und die Verbesserung der Lebensqualität durch die Reduktion der Schmerzintensität bewertet. Methodik: Retrospektive Analyse von 26 Patienten nach RFA eines OO und prospektive Analyse von 14 Patienten mittels eines selbstentwickelten Lebensqualität-Fragebogens. Es erfolgte die Aufarbeitung des Fragebogens, der elektronischen Patientenakte und der histopathologischen Befunde. Ergebnisse: Durchschnittlich vergangen 22 Monate zwischen erstem Auftreten von Beschwerden und der ursächlichen Therapie mittels RFA. Nach der RFA zeigte sich eine signifikante Reduktion der Schmerzsymptomatik und damit eine Steigerung der Lebensqualität. Unsere Ergebnisse bestätigen, dass die RFA von OO ein sicheres und effizientes Therapieverfahren ist. Diskussion: Um lange konservative Therapieversuche zu vermeiden und Auswirkungen auf das muskuloskeletale System zu vermindern sollte nach Diagnosestellung eine zeitnahe RFA des OO erfolgen