Literature review of the burden of prostate cancer in Germany, France, the United Kingdom and Canada.

BACKGROUND: Prostate cancer is the most frequently reported cancer in males in Europe, and is associated with substantial morbidity and mortality. The aim of the current review was to characterize the clinical, economic and humanistic burden of disease associated with prostate cancer in France, Germany, the UK and Canada. METHODS: Literature searches were conducted using the PubMed, EMBASE and Cochrane Library databases to identify studies reporting incidence and/or mortality rates, costs and health state utilities associated with prostate cancer in the settings of interest. For inclusion, studies were required to be published in English in full-text form from 2006 onwards. RESULTS: Incidence studies showed that in all settings the incidence of prostate cancer has increased substantially over the past two decades, driven in part by increased uptake of prostate specific antigen (PSA) screening leading to earlier identification of tumors, but which has also led to over-treatment, compounding the economic burden of disease. Mortality rates have declined over the same time frame, driven by earlier detection and improvements in treatment. Both prostate cancer itself, as well as treatment and treatment-related complications, are associated with reduced quality of life. CONCLUSIONS: Prostate cancer is associated with a significant clinical and economic burden, whilst earlier detection and aggressive treatment is associated with improved survival, over-treatment of men with indolent tumors compounds the already significant burden of disease and treatment can lead to long-term side effects including impotence and impaired urinary and/or bowel function. There is currently an unmet clinical need for diagnostic and/or prognostic tools that facilitate personalized prostate cancer treatment, and potentially reduce the clinical, economic and humanistic burden of invasive cancer treatment.

Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in Type 1 diabetes: a systematic review.

AIM: Continuous subcutaneous insulin infusion (CSII) is increasingly used in clinical practice for the management of selected patients with Type 1 diabetes. Several cost-effectiveness studies comparing CSII vs. multiple insulin injections (MDI) have been reported. The aim was systematically to review these analyses and test the hypothesis that CSII is a cost-effective use of healthcare resources across settings. METHODS: A literature review was performed using MEDLINE, Cochrane Library and other databases. No time limit or language restrictions were applied. After two rounds of screening, 11 cost-effectiveness analyses were included in the final review, of which nine used the CORE Diabetes Model. A narrative synthesis was conducted and mean cost effectiveness calculated. RESULTS: CSII was considered cost-effective vs. MDI in Type 1 diabetes in all 11 studies in 8 countries, with a mean (95% CI) incremental cost effectiveness ratio of €30 862 (17 997-43 727), US$40 143 (23 409-56 876) per quality-adjusted life year (QALY) gained. CSII was associated with improved life expectancy and quality-adjusted life expectancy (0.4-1.1 QALYs in adults), driven by lower HbA(1c) and lower frequency of hypoglycaemic events vs. MDI. CSII was associated with higher lifetime direct costs due to higher treatment costs but this was partially offset by cost-savings from reduced diabetes-related complications. CONCLUSIONS: Published cost-effectiveness analyses show that in Type 1 diabetes CSII is cost-effective vs. MDI across a number of settings for patients who have poor glycaemic control and/or problematic hypoglycaemia on MDI, with cost-effectiveness highly sensitive to the reduction in HbA1c and hypoglycaemia frequency associated with CSII.

Improving quality of care in people with Type 2 diabetes through the Associazione Medici Diabetologi-annals initiative: a long-term cost-effectiveness analysis.

AIMS: The Associazione Medici Diabetologi-annals initiative is a physician-led quality-of-care improvement scheme that has been shown to improve HbA1c concentration, blood pressure, lipid profiles and BMI in enrolled people with Type 2 diabetes. The present analysis investigated the long-term cost-effectiveness of enrolling people with Type 2 diabetes in the Associazione Medici Diabetologi-annals initiative compared with conventional management. METHODS: Long-term projections of clinical outcomes and direct costs (in 2010 Euros) were made using a published and validated model of Type 2 diabetes in people with Type 2 diabetes who were either enrolled in the Associazione Medici Diabetologi-annals initiative or who were receiving conventional management. Treatment effects were based on mean changes from baseline seen at 5 years after enrolment in the scheme. Costs and clinical outcomes were discounted at 3% per annum. RESULTS: The Associazione Medici Diabetologi-annals initiative was associated with improvements in mean discounted life expectancy and quality-adjusted life expectancy of 0.55 years (95% CI 0.54-0.57) years and 0.48 quality-adjusted life years (95% CI 0.46-0.49), respectively, compared with conventional management. Whilst treatment costs were higher in the Associazione Medici Diabetologi-annals arm, this was offset by savings as a result of the reduced incidence and treatment of diabetes-related complications. The Associazione Medici Diabetologi-annals initiative was found to be cost-saving over patient lifetimes compared with conventional management [€ 37,289 (95% CI 37,205-37,372) vs € 41,075 (95% CI 40,956-41,155)]. CONCLUSIONS: Long-term projections indicate that the physician-led Associazione Medici Diabetologi-annals initiative represents a cost-saving method of improving long-term clinical outcomes compared with conventional management of people with Type 2 diabetes in Italy.

A decision impact, decision conflict and economic assessment of routine Oncotype DX testing of 146 women with node-negative or pNImi, ER-positive breast cancer in the U.K.

BACKGROUND: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in early breast cancer patients. This study aims to examine the implications of routine Oncotype DX testing in the U.K. METHODS: Women with oestrogen receptor positive (ER+), pNO or pN1mi breast cancer were assessed for adjuvant chemotherapy and subsequently offered Oncotype DX testing, with changes in chemotherapy decisions recorded. A subset of patients completed questionnaires about their uncertainties regarding chemotherapy decisions pre- and post-testing. All patients were asked to complete a diary of medical interactions over the next 6 months, from which economic data were extracted to model the cost-effectiveness of testing. RESULTS: Oncotype DX testing resulted in changes in chemotherapy decisions in 38 of 142 (26.8%) women, with 26 of 57 (45.6%) spared chemotherapy and 12 of 85 (14.1%) requiring chemotherapy when not initially recommended (9.9% reduction overall). Decision conflict analysis showed that Oncotype DX testing increased patients' confidence in treatment decision making. Economic analysis showed that routine Oncotype DX testing costs £6232 per quality-adjusted life year gained. CONCLUSION: Oncotype DX decreased chemotherapy use and increased confidence in treatment decision making in patients with ER+ early-stage breast cancer. Based on these findings, Oncotype DX is cost-effective in the UK setting.

Evaluating the cost-effectiveness of laparoscopic adjustable gastric banding versus standard medical management in obese patients with type 2 diabetes in the UK.

AIM: To evaluate the cost-effectiveness of laparoscopic adjustable gastric banding (LAGB) versus standard medical management (SMM) in obese patients with type 2 diabetes from a UK healthcare payer perspective. METHODS: A validated computer model of diabetes was used to project outcomes reported from a randomized clinical trial of LAGB versus SMM in obese patients with type 2 diabetes. Two-year follow-up data from the trial were projected over a 40-year time horizon and cost-effectiveness was assessed from the perspective of the National Health Service. Future costs and clinical outcomes were discounted at 3.5% annually and all costs were reported in 2010 pounds sterling. A series of sensitivity analyses were performed. RESULTS: LAGB was associated with benefits in HbA1c, systolic blood pressure, body mass index and serum lipid concentrations, which led to significant increases in discounted life expectancy (an increase of 0.64 years) and quality-adjusted life expectancy (an increase of 0.92 quality-adjusted life years, QALYs) and reduced incidence of diabetes complications relative to SMM. Treatment costs in the LAGB arm increased by 4552 Great British Pounds (GBP), but this was partially offset by cost savings resulting from a reduction in the incidence of all modelled diabetes complications. The incremental cost-effectiveness ratio of GBP 3602 per QALY in the base case fell well below commonly quoted willingness-to-pay thresholds in the UK setting. CONCLUSIONS: On the basis of data from a recent randomized controlled trial, LAGB is likely to be considered cost-effective from the healthcare payer perspective when compared with SMM of obesity in patients with type 2 diabetes in the UK setting.

Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.

Over 4 million patients suffer nosocomial infections annually in the European Union. This study aimed to estimate the healthcare burden associated with healthcare-associated infections (HAIs) following surgery in France, and explore the potential impact of infection control strategies and interventions on the clinical and economic burden of disease. Data on the frequency of HAIs were gathered from the 2010 Programme de Médicalisation des Systèmes d'Information (PMSI), and cost data were taken from the 2009 Echelle Nationale de Coûts à Méthodologie Commune (ENCC). It was estimated that 3% of surgical procedures performed in 2010 in France resulted in infection, resulting in an annual cost of €57 892 715. Patients experiencing a HAI had a significantly increased mortality risk (4.15-fold) and an increased length of hospital stay (threefold). Scenario analysis in which HAI incidence following surgery was reduced by 8% (based on a study of the effectiveness of triclosan-coated sutures), suggested that, annually, 20 205 hospital days and €4 588 519 could be saved. Analyses of 20% and 30% reductions in incidence (based on an estimate of the number of preventable nosocomial infections) suggested that annual savings of €11 548 057 and €17 334 696, respectively, could be made. New infection control interventions which reduce HAI incidence during hospitalization for surgery have the potential to provide valuable cost savings to healthcare providers.

Evaluating the cost-effectiveness of reduced mild hypoglycaemia in subjects with Type 1 diabetes treated with insulin detemir or NPH insulin in Denmark, Sweden, Finland and the Netherlands.

AIMS: To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. METHODS: A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of mild hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was calculated in terms of quality-adjusted life expectancy. Pharmacy costs were accounted using published prices and defined daily doses for both insulins. Costs were expressed in 2010 euros (€). RESULTS: Treatment with insulin detemir was associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of 26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality-adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life years (standard deviation). Annual costs were € 573.55 (110.42) vs. € 332.76 (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These values were € 545.79 (106.54) vs. € 306.12 (57.78) in Sweden, € 720.10 (140.74) vs. € 408.73 (78.61) in Finland and € 584.01 (109.47) vs. € 359.60 (64.84) in the Netherlands. Incremental cost-effectiveness ratios were approximately € 12,644 (Denmark), € 12,612 (Sweden), € 16,568 (Finland) and € 12,216 (the Netherlands) per quality-adjusted life year gained for insulin detemir vs. NPH insulin. CONCLUSIONS: Insulin detemir is likely to be cost-effective vs. NPH insulin in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Increased pharmacy costs with insulin detemir should not be a barrier to therapy based on these findings.

Cost-utility analysis of liraglutide compared with sulphonylurea or sitagliptin, all as add-on to metformin monotherapy in Type 2 diabetes mellitus.

AIM: To investigate the cost-effectiveness of liraglutide as add-on to metformin vs. glimepiride or sitagliptin in patients with Type 2 diabetes uncontrolled with first-line metformin. METHODS: Data were sourced from a clinical trial comparing liraglutide vs. glimepiride, both in combination with metformin, and a clinical trial comparing liraglutide vs. sitagliptin, both as add-on to metformin. Only the subgroup of patients in whom liraglutide was added to metformin monotherapy was included in the cost-utility analysis. The CORE Diabetes Model was used to simulate outcomes and costs with liraglutide 1.2 and 1.8 mg vs. glimepiride and vs. sitagliptin over patients' lifetimes. Treatment effects were taken directly from the trials. Costs and outcomes were discounted at 3.5% per annum and costs were accounted from a third-party payer (UK National Health System) perspective. RESULTS: Treatment with liraglutide 1.2 and 1.8 mg resulted, respectively, in mean increases in quality-adjusted life expectancy of 0.32 ± 0.15 and 0.28 ± 0.14 quality-adjusted life years vs. glimepiride, and 0.19 ± 0.15 and 0.31 ± 0.15 quality-adjusted life years vs. sitagliptin, and was associated with higher costs of £ 3003 ± £ 678 and £ 4688 ± £ 639 vs. glimepiride, and £ 1842 ± £ 751 and £ 3224 ± £ 683 vs. sitagliptin, over a patient's lifetime. Both liraglutide doses were cost-effective, with incremental cost-effectiveness ratios of £ 9449 and £ 16,501 per quality-adjusted life year gained vs. glimepiride, and £ 9851 and £ 10,465 per quality-adjusted life year gained vs. sitagliptin, respectively. CONCLUSIONS: Liraglutide, added to metformin monotherapy, is a cost-effective option for the treatment of Type 2 diabetes in a UK setting.

Costs and where to find them: identifying unit costs for health economic evaluations of diabetes in France, Germany and Italy.

BACKGROUND: Health economic evaluations require cost data as key inputs. Many countries do not have standardized reference costs so costs used often vary between studies, thereby reducing transparency and transferability. The present review provided a comprehensive overview of cost sources and suggested unit costs for France, Germany and Italy, to support health economic evaluations in these countries, particularly in the field of diabetes. METHODS: A literature review was conducted across multiple databases to identify published unit costs and cost data sources for resource items commonly used in health economic evaluations of antidiabetic therapies. The quality of unit cost reporting was assessed with regard to comprehensiveness of cost reporting and referencing as well as accessibility of cost sources from published cost-effectiveness analyses (CEA) of antidiabetic medications. RESULTS: An overview of cost sources, including tariff and fee schedules as well as published estimates, was developed for France, Germany and Italy, covering primary and specialist outpatient care, emergency care, hospital treatment, pharmacy costs and lost productivity. Based on these sources, unit cost datasets were suggested for each country. The assessment of unit cost reporting showed that only 60% and 40% of CEAs reported unit costs and referenced them for all pharmacy items, respectively. Less than 20% of CEAs obtained all pharmacy costs from publicly available sources. CONCLUSIONS: This review provides a comprehensive account of available costs and cost sources in France, Germany and Italy to support health economists and increase transparency in health economic evaluations in diabetes.

Cost-effectiveness of Lutetium [177Lu] oxodotreotide versus best supportive care with octreotide in patients with midgut neuroendocrine tumors in France.

BACKGROUND AND AIMS: In France, there are approximately 2,400 new cases of neuroendocrine tumors (NETs) annually. Peptide receptor radionuclide therapy with 177Lu-Dotatate plus long-acting repeatable [LAR] octreotide 30 mg has been shown to significantly improve progression-free survival and overall survival relative to high-dose octreotide LAR 60 mg in patients with unresectable or metastatic progressive midgut NETs. A long-term cost-effectiveness analysis was performed to assess whether 177Lu-Dotatate is a cost-effective option versus octreotide 60 mg for patients with unresectable/metastatic progressive midgut NETs from the perspective of French healthcare payer. METHODS: The analysis was performed using a three-state partitioned survival model. In the base case analysis 177Lu-Dotatate plus octreotide LAR 30 mg was compared with high-dose octreotide LAR 60 mg in patients with midgut NETs. Survival data were obtained from the phase III NETTER-1 trial in patients with metastatic midgut NETs. Future costs and clinical outcomes were discounted at 4% per annum. One-way deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case analysis, for patients with midgut NETs, 177Lu-Dotatate treatment improved quality-adjusted life expectancy by 1.21 quality-adjusted life years (QALYs) relative to octreotide LAR 60 mg and the lifetime treatment costs were EUR 50,784 higher with 177Lu-Dotatate resulting in an incremental cost-effectiveness ratio (ICER) of EUR 42,106 per QALY gained versus octreotide LAR 60 mg. When compared with everolimus, 177Lu-Dotatate was associated with an ICER of EUR 59,769 per QALY gained. Sensitivity analyses showed that the results were sensitive to methods used to extrapolate survival data. CONCLUSIONS: For patients with advanced progressive midgut NETs 177Lu-Dotatate is likely to be considered a cost-effective option versus octreotide 60 mg from the perspective of the French healthcare payer.

Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis.

Aims: The efficacy and safety of oral semaglutide, the first glucagon-like peptide-1 (GLP-1) receptor agonist developed for oral administration for the treatment of type 2 diabetes, was evaluated in the PIONEER clinical trial program, and a recently published network meta-analysis allowed comparison with further injectable GLP-1 receptor agonists. The present study aimed to assess the short-term cost- effectiveness of oral semaglutide 14 mg versus subcutaneous once-weekly dulaglutide 1.5 mg, once-weekly exenatide 2 mg, twice-daily exenatide 10 µg, once-daily liraglutide 1.8 mg, once-daily lixisenatide 20 µg, and once-weekly semaglutide 1 mg, in terms of the cost per patient achieving glycated hemoglobin (HbA1c) targets (cost of control).Materials and methods: Cost of control was calculated by dividing the annual treatment costs associated with an intervention by the proportion of patients achieving the treatment target with an intervention, with outcomes calculated for targets of HbA1c ≤6.5% and HbA1c <7.0% for all included GLP-1 receptor agonists. Annual treatment costs were accounted in 2019 United States dollars (USD), based on 2019 wholesale acquisition cost.Results: For the treatment target of HbA1c ≤6.5%, once-weekly semaglutide 1 mg and oral semaglutide 14 mg were associated with the lowest costs of control, at USD 15,430 and USD 17,383 per patient achieving target, respectively. Similarly, the cost of control was lowest with once-weekly semaglutide 1 mg at USD 12,627 per patient achieving target, followed by oral semaglutide 14 mg at USD 13,493 per patient achieving target for the target of HbA1c <7.0%. All other interventions were associated with higher cost of control values for both targets.Conclusions: Oral semaglutide 14 mg is likely to be cost-effective versus dulaglutide, exenatide (once weekly and twice daily), liraglutide, and lixisenatide in terms of bringing people with type 2 diabetes to glycemic control targets of HbA1c ≤6.5% and HbA1c <7.0% in the US.

An estimation of the long-term clinical and economic benefits of insulin lispro in Type 1 diabetes in the UK.

AIMS: To determine the long-term health economic benefits associated with lispro vs. regular human insulin (RHI) in UK Type 1 diabetic (T1DM) patients using the previously published and validated CORE Diabetes Model. METHODS: A literature review designed to capture clinical benefits associated with lispro and T1DM cohort characteristics specific to UK was undertaken. Clinical benefits were derived from a Cochrane meta-analysis. The estimated difference (weighted mean) in glycated haemoglobin (HbA(1c)) was -0.1% (95% confidence interval -0.2 to 0.0%) for lispro vs. RHI. Severe hypoglycaemia rates for lispro and RHI were 21.8 and 46.1 events per 100 patient years, respectively. Costs and disutilities were accounted for severe hypoglycaemia rates. All costs were accounted in 2007 poundUK from a National Health Service (NHS) perspective. Future costs and clinical benefits were discounted at 3.5% annually. RESULTS: In the base-case analysis, lispro was projected to be dominant compared with RHI. Lispro was associated with improvements in quality-adjusted life expectancy (QALE) of approximately 0.10 quality-adjusted life years (QALYs) vs. RHI (7.60 vs. 7.50 QALYs). Lifetime direct medical costs per patient were lower with lispro treatment, pound70 576 vs. pound72 529. Severe hypoglycaemia rates were the key driver in terms of differences in QALE and lifetime costs. Sensitivity analyses with assumptions around time horizon, discounting rates and benefits in terms of glycaemic control or hypoglycaemic event rates revealed that lispro remained dominant. CONCLUSIONS: Our findings suggest that lispro is likely to improve QALE, reduce frequency of diabetes-related complications and lifetime medical costs compared with RHI.

Hereditary hemolytic anemia with increased red cell adenosine deaminase (45- to 70-fold) and decreased adenosine triphosphate.

Hereditary hemolytic anemia, a dominantly transmitted disorder, has affected 12 family members spanning three generations. The concentration of adenosine triphosphate in the red cells was about half that of comparably reticulocyte-rich blood. Since adenosine deaminase and adenosine kinase compete for a common substrate, the greatly increased activity of the former may interfere with nucleotide salvage via the latter.

Cost-effectiveness of pioglitazone in patients with type 2 diabetes and a history of macrovascular disease in a Swiss setting.

OBJECTIVES: To evaluate the cost-effectiveness of pioglitazone versus placebo, given in addition to existing treatment regimens, in patients with type 2 diabetes and evidence of macrovascular disease in Switzerland. METHODS: Event rates corresponding to macrovascular outcomes from the PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events) trial of pioglitazone were used to project long-term clinical outcomes as part of a modified version of the previously validated CORE Diabetes Model. Direct medical costs associated with treatment regimens, complications and patient management were accounted in 2005 values based on Swiss-specific unit costs. Time horizon was set to lifetime (35 years). Future costs and clinical benefits were discounted at 2.5% annually in line with Swiss recommendations. One-way sensitivity analyses were performed. RESULTS: Addition of pioglitazone was associated with a reduced incidence of most diabetes-related complications, improved life expectancy (0.258 years) and improved quality-adjusted life expectancy (0.180 QALYs) compared with placebo. Pioglitazone treatment increased direct costs by CHF 10,914 per patient over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) of pioglitazone versus placebo was CHF 42,274 per life-year gained and CHF 60,596 per QALY gained. ICERs were sensitive to variation in time horizon and duration of pioglitazone treatment effects. With a willingness to pay of CHF 80,000 per QALY in the Swiss setting, there was a 62.5% chance that pioglitazone would be cost-effective. CONCLUSIONS: Addition of pioglitazone to existing therapy was projected to reduce the long-term cumulative incidence of most diabetes complications and improve quality-adjusted life expectancy. Evaluation of incremental direct medical costs associated with these clinical benefits indicated that pioglitazone is likely to be a cost-effective treatment option in the Swiss setting over patient lifetimes.

Exenatide versus insulin glargine: a cost-effectiveness evaluation in patients with Type 2 diabetes in Switzerland.

OBJECTIVES: To investigate the long-term clinical and economic outcomes associated with exenatide versus insulin glargine as "add-on" treatments to oral therapy in individuals with Type 2 diabetes inadequately controlled with combination oral agents in the Swiss setting. METHODS: A computer simulation model of diabetes was used to project complications, life expectancy, quality-adjusted life expectancy and direct medical costs over a 35-year time horizon. Cohort characteristics and treatment effect data were derived from a 26-week randomized clinical trial comparing exenatide and insulin glargine. Modeled treatment effects included reductions in glycosylated hemoglobin (HbA1c) by -0.99% and -1.07% and in body mass index (BMI) by -0.80 and +0.55 kg/m2 with exenatide and insulin glargine respectively. Changes in systolic blood pressure and serum lipid levels were also captured. Simulations incorporated published quality of life utilities and Swiss costs from 2006. Extensive sensitivity analyses were conducted to assess the robustness of projected outcomes. Future clinical and economic outcomes were discounted at 2.5% per annum. RESULTS: In the base-case analysis exenatide was associated with comparable life expectancy (11,549 years versus 11,468 years) and an improvement in quality-adjusted life expectancy of 0.43 quality-adjusted life years (QALYs) versus insulin glargine over a 35-year time horizon. Exenatide was associated with a reduced cumulative incidence of most diabetes-related complications including an absolute reduction in myocardial infarction by 0.28%. Assuming an annual treatment cost of CHF 2,797.74 for exenatide, direct costs increased by CHF 8,378 per patient over the 35-year time horizon compared to insulin glargine. The resultant incremental cost-effectiveness ratio was CHF 19,450 per QALY gained for exenatide versus insulin glargine. CONCLUSIONS: Exenatide was associated with comparable life expectancy and an improvement in quality-adjusted life expectancy versus insulin glargine over a 35-year time horizon. Based on current standards exenatide would be a cost-effective treatment alternative to insulin glargine in Switzerland for Type 2 diabetes patients inadequately controlled on oral therapy.

Cost of achieving HbA1c and weight loss treatment targets with IDegLira vs insulin glargine U100 plus insulin aspart in the USA.

BACKGROUND: Compared with basal-bolus insulin therapy (insulin glargine U100 plus insulin aspart), IDegLira has been shown to be associated with similar improvements in HbA1c, with superior weight loss and reduced hypoglycemia in patients with type 2 diabetes. The present analysis evaluated the cost per patient with type 2 diabetes achieving HbA1c-focused and composite treatment targets with IDegLira and insulin glargine U100 plus insulin aspart (≤4 times daily). METHODS: The proportions of patients achieving treatment targets were obtained from the treat-to-target, non-inferiority DUAL VII study (NCT02420262). The annual cost per patient achieving target (cost of control) was analyzed from a US healthcare payer perspective. The annual cost of control was assessed for eight prespecified endpoints and four post-hoc endpoints. RESULTS: The number needed to treat to bring one patient to targets of HbA1c <7.0% and HbA1c ≤6.5% was similar with IDegLira and insulin glargine U100 plus insulin aspart. However, when weight gain and/or hypoglycemia were included, the number needed to treat was lower with IDegLira. IDegLira and insulin glargine U100 plus insulin aspart had similar costs of control for HbA1c <7.0%. However, cost of control values were substantially lower with IDegLira when the more stringent target of HbA1c ≤6.5% was used, and when patient-centered outcomes of hypoglycemia risk and impact on weight were included. CONCLUSION: IDegLira was shown to be a cost-effective treatment vs insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic targets on basal insulin in the USA.

Lysophosphatidic acid-induced platelet shape change revealed through LPA(1-5) receptor-selective probes and albumin.

Lysophosphatidic acid (LPA), a component of mildly-oxidized LDL and the lipid rich core of atherosclerotic plaques, elicits platelet activation. LPA is the ligand of G protein-coupled receptors (GPCR) of the EDG family (LPA(1-3)) and the newly identified LPA(4-7) subcluster. LPA(4), LPA(5) and LPA(7) increase cellular cAMP levels that would induce platelet inhibition rather than activation. In the present study we quantified the mRNA levels of the LPA(1-7) GPCR in human platelets and found a rank order LPA(4) = LPA(5) > LPA(7) > LPA(6) = LPA(2) >> LPA(1) > LPA(3). We examined platelet shape change using a panel of LPA receptor subtype-selective agonists and antagonists and compared them with their pharmacological profiles obtained in heterologous LPA(1-5) receptor expression systems. Responses to different natural acyl and alkyl species of LPA, and octyl phosphatidic acid analogs, alpha-substituted phosphonate analogs, N-palmitoyl-tyrosine phosphoric acid, N-palmitoyl-serine phosphoric acid were tested. All of these compounds elicited platelet activation and also inhibited LPA-induced platelet shape change after pre-incubation, suggesting that receptor desensitization is likely responsible for the inhibition of this response. Fatty acid free albumin (10 microM) lacking platelet activity completely inhibited platelet shape change induced by LPA with an IC(50) of 1.1 microM but had no effect on the activation of LPA(1,2,3,&5) expressed in endogenously non-LPA-responsive RH7777 cells. However, albumin reduced LPA(4) activation and shifted the dose-response curve to the right. LPA(5) transiently expressed in RH7777 cells showed preference to alkyl-LPA over acyl-LPA that is similar to that in platelets. LPA did not increase cAMP levels in platelets. In conclusion, our results with the pharmacological compounds and albumin demonstrate that LPA does not induce platelet shape change simply through activation of LPA(1-5), and the receptor(s) mediating LPA-induced platelet activation remains elusive.

Biphasic insulin aspart 70/30 vs. insulin glargine in insulin naïve type 2 diabetes patients: modelling the long-term health economic implications in a Swedish setting.

OBJECTIVES: To evaluate the long-term clinical and economic outcomes of biphasic insulin aspart 70/30 (BIAsp 70/30) treatment vs. insulin glargine in insulin naïve, type 2 diabetes patients failing oral antidiabetic drugs in a Swedish setting. METHODS: A published and validated computer simulation model (the CORE Diabetes Model) was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over patient lifetimes. Cohort characteristics [54.5% male, mean age 52.4 years, 9 years mean diabetes duration, mean glycosylated haemoglobin (HbA1c) 9.77%] and treatment effects were based on results from the Initiate Insulin by Aggressive Titration and Education (INITIATE) clinical trial. Direct medical costs were accounted in 2006 Swedish Kronor (SEK) and economic and clinical benefits were discounted at 3% per annum. RESULTS: Biphasic insulin aspart 70/30 treatment when compared with insulin glargine treatment was associated with improvements in discounted life expectancy of 0.21 years (13.10 vs. 12.89 years) and QALE of 0.21 quality-adjusted life years (QALYs) (9.16 vs. 8.96 QALYs). Reductions in the incidence of diabetes-related complications in the BIAsp 70/30 treatment arm led to reduced total costs of SEK 10,367 when compared with insulin glargine (SEK 396,475 vs. SEK 406,842) over patient lifetimes. BIAsp 70/30 treatment was projected to be dominant (cost and lifesaving) when compared with insulin glargine in the base case analysis. CONCLUSIONS: Biphasic insulin aspart 70/30 treatment was associated with improved clinical outcomes and reduced costs compared with insulin glargine treatment over patient lifetimes. These results were driven by improved HbA1c levels associated with BIAsp 70/30 compared with insulin glargine and the accompanying reduction in diabetes-related complications despite increases in body mass index.

Lead poisoning. Further observations on erythrocyte pyrimidine-nucleotidase deficiency and intracellular accumulation of pyrimidine nucleotides.

Pyrimidine nucleotides, detectable in normal erythrocytes only in trace quantities if at all, were found to comprise 7-80% of the intracellular nucleotide pools in nine subjects with severe lead over-burden. Blood lead concentrations ranged from approximately equal to 200- to 400-microgram/dl packed cells, and the greatest accumulations of pyrimidine-containing nucleotides occurred in the two subjects with the highest blood lead levels. Most of the patients had mild or moderate anemia and moderate basophilic stippling evident in Wright's-stained peripheral smears. Pyrimidine nucleotidase activities were inhibited to 13-28% of the mean activity in normal control erythrocytes and even more so (5-15%) when compared to specimens with increased reticulocytes and young cells. Reticulocytosis was absent in two subjects and modest to moderate in the remainder, but erythrocyte assays revealed the substantial elevations in populations of young mean cell age. Inappropriately low reticulocyttial elevations in glucose-6-phosphate dehydrogenase expected in populations of young mean cell age. Inappropriately low reticulocyte responses may reflect hematopoietic suppressive effects of lead at a variety of metabolic loci.