Aims/hypothesis: This study estimated the economic efficiency (1) of intensive blood glucose control and tight blood pressure control in patients with type 2 diabetes who also had hypertension, and (2) of metformin therapy in type 2 diabetic patients who were overweight. Methods: We conducted cost-utility analysis based on patient-level data from a randomised clinical controlled trial involving 4,209 patients with newly diagnosed type 2 diabetes conducted in 23 hospital-based clinics in England, Scotland and Northern Ireland as part of the UK Prospective Diabetes Study (UKPDS). Three different policies were evaluated: intensive blood glucose control with sulphonylurea/insulin; intensive blood glucose control with metformin for overweight patients; and tight blood pressure control of hypertensive patients. Incremental cost:effectiveness ratios were calculated based on the net cost of healthcare resources associated with these policies and on effectiveness in terms of quality-adjusted life years gained, estimated over a lifetime from within-trial effects using the UKPDS Outcomes Model. Results: The incremental cost per quality-adjusted life years gained (in year 2004 UK prices) for intensive blood glucose control was \u00a36,028, and for blood pressure control was \u00a3369. Metformin therapy was cost-saving and increased quality-adjusted life expectancy. Conclusions/interpretation: Each of the three policies evaluated has a lower cost per quality-adjusted life year gained than that of many other accepted uses of healthcare resources. The results provide an economic rationale for ensuring that care of patients with type 2 diabetes corresponds at least to the levels of these interventions. \u00a9 Springer-Verlag 2005.
\n \n\n \n \nAims/hypothesis. The aim of this study was to develop a simulation model for Type 2 diabetes that can be used to estimate the likely occurrence of major diabetes-related complications over a lifetime, in order to calculate health economic outcomes such as quality-adjusted life expectancy. Methods. Equations for forecasting the occurrence of seven diabetes-related complications and death were estimated using data on 3642 patients from the United Kingdom Prospective Diabetes Study (UKPDS). After examining the internal validity, the UKPDS Outcomes Model was used to simulate the mean difference in expected quality-adjusted life years between the UKPDS regimens of intensive and conventional blood glucose control. Results. The model's forecasts fell within the 95% confidence interval for the occurrence of observed events during the UKPDS follow-up period. When the model was used to simulate event history over patients' lifetimes, those treated with a regimen of conventional glucose control could expect 16.35 undiscounted quality-adjusted life years, and those receiving treatment with intensive glucose control could expect 16.62 quality-adjusted life years, a difference of 0.27 (95% CI: -0.48 to 1.03). Conclusions/interpretations. The UKPDS Outcomes Model is able to simulate event histories that closely match observed outcomes in the UKPDS and that can be extrapolated over patients' lifetimes. Its validity in estimating outcomes in other groups of patients, however, remains to be evaluated. The model allows simulation of a range of long-term outcomes, which should assist in informing future economic evaluations of interventions in Type 2 diabetes.
\n \n\n \n \nOBJECTIVE - Patients with diabetes have a higher case fatality rate in myocardial infarction (MI) or stroke than those without diabetes: that is, MI and stroke are more often fatal if diabetes is present. We investigated whether the risk of MI or stroke being fatal in type 2 diabetes can be estimated using information available around the time diabetes is diagnosed. RESEARCH DESIGN AND METHODS - Analyses were based on 674 cases of MI (351 fatal) that occurred in 597 of 5,102 U.K. Prospective Diabetes Study (UKPDS) patients for whom covariate data were available during a median follow-up of 7 years. Multivariate logistic regression was used to examine differences in risk factors, measured within 2 years of diagnosis of diabetes, between fatal and nonfatal MI. Similar analyses were performed for 234 strokes (48 fatal) that occurred in 199 patients. RESULTS - Patients with fatal MI had higher HbA 1c, than those with nonfatal MI (odds ratio 1.17 per 1% HbA 1c, P = 0.014). Patients with fatal stroke had higher HbA 1c than those with nonfatal stroke (odds ratio 1.37 per 1% HbA 1c, P = 0.007). Other risk factors for MI case fatality included increased age, blood pressure, and urine albumin level. CONCLUSlONS - The risk of MI or stroke being fatal in type 2 diabetes is associated with risk factors, including HbA1c, measured many years before onset of MI or stroke. Equations have been added to the UKPDS Risk Engine to estimate likely case fatality rates in MI and stroke.
\n \n\n \n \nCygnus is a two-axis radiographic x-ray facility designed to drive rod-pinch diode loads at 2.25 MV with a spot size of about 1 mm producing 4 Rads at 1 meter. This x-ray source was developed to support the Sub-Critical Experiments Program (SCE) at the Nevada Test Site (NTS) and is distinguished from other commercially available sources by a dramatically reduced spot size for high resolution radiography, higher reliability, and compact size and modularity for greater layout flexibility to fit within the size constraints of its ultimate underground site location. The facility is composed of two virtually identical machines referred to as Cygnus 1 and Cygnus 2 that incorporate proven pulsed power technology. Each machine employs a Marx generator, Pulse Forming Line (pfl), Water Coax Transmission Line, and Inductive Voltage Adder (IVA) that drive a high vacuum rod-pinch diode. The pfl design was originally developed for the Radiographic Integrated Test stand (RITS) and the IVA cells are from the Sandia SABRE accelerator. The Cygnus 1 machine was constructed and fielded at the Los Alamos National Laboratory to undergo pulsed power component and reliability testing and for use to develop and optimize the rod-pinch diode load. Later, Cygnus 2 was constructed and fielded at Titan-PSD for testing employing the changes and modifications that resulted from of the Cygnus 1 tests. At the time of this writing, Cygnus 2 has undergone testing of the pulsed power components up through the output of the water line where a dummy load was placed. A pulse has not yet been propagated through the water coax to the diode. This paper describes and compares the pulsed power performance of both Cygnus machines up to the output of the water line. The Cygnus testing program is a result of the cooperative effort of Titan PSD, Sandia National Laboratory, Los Alamos National Laboratory, and Bechtel Nevada.
\n \n\n \n \nWhen a published statistical model is also distributed as computer software, it will usually be desirable to present the outputs as interval, as well as point, estimates. The present paper compares three methods for approximate interval estimation about a model output, for use when the model form does not permit an exact interval estimate. The methods considered are first-order asymptotics, using second derivatives of the log-likelihood to estimate variance information; higher-order asymptotics based on the signed-root transformation; and the non-parametric bootstrap. The signed-root method is Bayesian, and uses an approximation for posterior moments that has not previously been tested in a real-world application. Use of the three methods is illustrated with reference to a software project arising in medical decision-making, the UKPDS Risk Engine. Intervals from the first-order and signed-root methods are near-identical, and typically 1% wider to 7% narrower than those from the non-parametric bootstrap. The asymptotic methods are markedly faster than the bootstrap method.
\n \n\n \n \nBackground. The progression of nephropathy from diagnosis of type 2 diabetes has not been well described from a single population. This study sought to describe the development and progression through the stages of microalbuminuria, macroal-buminuria, persistently elevated plasma creatinine or renal replacement therapy (RRT), and death. Methods. Using observed and modeled data from 5097 subjects in the UK Prospective Diabetes Study, we measured the annual probability of transition from stage to stage (incidence), prevalence, cumulative incidence, ten-year survival, median duration per stage, and risk of death from all-causes or cardiovascular disease. Results. From diagnosis of diabetes, progression to micro-albuminuria occurred at 2.0% per year, from microalbuminuria to macroalbuminuria at 2.8% per year, and from macroalbu-minuria to elevated plasma creatinine (\u2265175 \u03bcmol/L) or renal replacement therapy at 2.3% per year. Ten years following diagnosis of diabetes, the prevalence of microalbuminuria was 24.9%, of macroalbuminuria was 5.3%, and of elevated plasma creatinine or RRT was 0.8%. Patients with elevated plasma creatinine or RRT had an annual death rate of 19.2% (95% confidence interval, CI, 14.0 to 24.4%). There was a trend for increasing risk of cardiovascular death with increasing nephropathy (P < 0.0001), with an annual rate of 0.7% for subjects in the stage of no nephropathy, 2.0% for those with micro-albuminuria, 3.5% for those with macroalbuminuria, and 12.1% with elevated plasma creatinine or RRT. Individuals with macro-albuminuria were more likely to die in any year than to develop renal failure. Conclusions. The proportion of patients with type 2 diabetes who develop microalbuminuria is substantial with one quarter affected by 10 years from diagnosis. Relatively fewer patients develop macroalbuminuria, but in those who do, the death rate exceeds the rate of progression to worse nephropathy.
\n \n\n \n \n