Harold Hosker

A Cox Regression Analysis of Covariates for Asthma Hospital Readmissions

Background. Asthma hospital admissions and readmissions are unacceptably high, thus, a method to identify those at greatest risk could be helpful. Methods. An observational retrospective study using a Cox regression to determine the relationship between the time interval between admissions and possible covariates of a readmission. The covariates were age, sex, ethnicity, smoking habit, history of allergy or eczema/hay fever, age of onset, Townsend index (TI), Jarman score (JS), and drugs on discharge. Those with p<0.2, together with interacting covariates, from the preliminary analysis were eligible for the multivariate Cox regression analysis. Results. Of the 523 patients admitted between 1994 and 1998 because of their asthma, complete data were available for 440. Of these, 112 were readmitted. Eligible covariates for the multivariate Cox regression analysis were sex, allergy status, history of eczema/hay fever, the JS and TI together with interactions between JS and TI, JS and allergy, and allergy with eczema/hay fever. There were 278 subjects (71 with a readmission) with complete data for these eligible covariates. The multivariate analysis revealed that female sex (odds ratio [OR] = 2.65, 95% confidence interval [CI] 1.42, 4.92), high JS (OR = 2.03, 95% CI 1.13–3.65), and history of allergy (OR = 1.88, 95% CI 1.06–3.32) formed the final model as significant predictors of readmission. Conclusion. Females with a history of allergy that were registered at a practice with a high workload (JS) had a higher risk of readmission. The analysis method used highlights how those at risk of readmission can be identified so that they can be targeted post discharge.

Determination of the relative bioavailability of salbutamol to the lungs following inhalation from dry powder inhaler formulations containing drug substance manufactured by supercritical fluids and micronization

PurposeThe relative lung bioavailability of salbutamol sulfate particles produced using supercritical fluids (SEDS™) and delivered by dry powder inhaler (DPI) was compared with the performance of a conventional micronized drug DPI using the same device design (Clickhaler™, Innovata Biomed).Materials and MethodsTwelve healthy volunteers and 11 mild asthmatic patients completed separate four-way randomised cross-over studies, assessing the relative bioavailability of salbutamol sulfate (urinary excretion method), formulated as SEDS™ particles (three batches) and micronized particles (Asmasal™ inhaler, UCB Pharma Ltd). Post-treatment improvements in patient lung function were assessed by measuring FEV1. Physicochemical evaluation of the three SEDS™ batches revealed inter-batch differences in particle size and shape.ResultsThere was no significant difference in the relative lung bioavailability of salbutamol and its bronchodilator response between the best performing SEDS™ formulation and the Asmasal™ inhaler in volunteers and patients, respectively. SEDS™ salbutamol sulfate showing wafer like morphology gave greater fine particle dose, relative lung bioavailability and enhanced bronchodilation compared to other SEDS™ batches containing elongated particles.ConclusionsActive Pharmaceutical Ingredient (API) manufactured using supercritical fluids and delivered by DPI can provide similar lung bioavailability and clinical effect to the conventional micronized commercial product. Product performance is however notably influenced by inter-batch differences in particle characteristics.