Increasing the efficiency of Monte Carlo cohort simulations with variance reduction techniques.

The authors discuss techniques for Monte Carlo (MC) cohort simulations that reduce the number of simulation replications required to achieve a given degree of precision for various output measures. Known as variance reduction techniques, they are often used in industrial engineering and operations research models, but they are seldom used in medical models. However, most MC cohort simulations are well suited to the implementation of these techniques. The authors discuss the cost of implementation versus the benefit of reduced replications.     

Management of asthma in patients supervised by primary care physicians or by specialists.

French asthma patients may be supervised by general practitioners (GPs) and/or specialists. Therefore, this study examined asthma management in patients exclusively supervised by specialists (SPE), GPs, (GP) and both (GP+SPE group), and compared the findings. Asthma patients were consecutively recruited in 348 pharmacies. Each patient completed a questionnaire providing data on personal characteristics, asthma management, perception of disease and asthma supervision. Asthma control was measured using the Asthma Control Test. Questionnaires were linked to computerised records of medications which had been dispensed before inclusion in the study. From the 1,256 patients (mean age = 36.1 yrs, 54.3% females), 11.4, 36.6, and 52.0% were placed in the SPE, GP, and GP+SPE groups, respectively. During the previous 4 weeks, most patients in the SPE group were properly controlled (52.2 versus 26.4 and 21.5% in GP and GP+SPE groups, respectively). The SPE group made more use of fixed combinations of long-acting beta agonist and inhaled corticosteroid, while receiving less short-acting beta agonists, antitussives and antibiotics. Striking differences in symptoms and asthma management were observed according to the type of asthma supervision. The current results strongly support the need to improve the management of asthma in primary care, and the coordination of care between general practitioners and specialists.     

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.     

The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study.

AIMS: To examine the effects of agents that alter potassium adenosine triphosphate (KATP) channel activity in beta-cells on cognitive function and counterregulatory hormone responses during acute hypoglycaemia, given the physiological similarities between the pancreatic beta-cell and the hypothalamic glucose-sensitive neurones (GSN) and the widespread distribution of sulphonylurea receptors in neuronal cells throughout the brain. METHODS: Ten healthy males were studied on four occasions and in random order underwent three stepped hypoglycaemic (plasma glucose aims: 3.4, 2.8, 2.4 mmol/l) and one euglycaemic (plasma glucose aim: 5 mmol/l) insulin clamps. Prior to each hypoglycaemic study, volunteers received either 10 mg glibenclamide, or 5 mg/kg diazoxide or placebo orally. Cognitive function, symptom scores and counterregulatory hormone responses were measured at each glycaemic level. RESULTS: There was no statistically significant effect of either drug on the symptoms generated or the counterregulatory hormonal response during hypoglycaemia. However, cognitive function was better preserved during hypoglycaemia in the glibenclamide-treated arm, particularly four-choice reaction time which deteriorated at a plasma glucose 2.5 mmol/l compared with 3.0 mmol/l with diazoxide (P = 0.015) and 2.9 mmol/l with placebo (P = 0.114). CONCLUSIONS: Single doses of pharmacological agents which alter membrane KATP channel activity do not affect the counterregulatory response to hypoglycaemia but may modify cognitive function during cerebral glucopenia. The unexpected effects of glibenclamide on cortical function suggest a novel action of sulphonylureas that warrants further investigation.