The size of microcapsules is a critical parameter in the immunoisolation of islets of Langerhans by microencapsulation. The use of smaller capsules decreases the total implant volume and improves insulin kinetics and oxygen supply. A high voltage electrostatic pulse system was used for the production of small (< 300 microns) alginate beads, the first step of the encapsulation technique. However, islets often protruded from capsules that were too small, further emphasizing the need for a method to control bead size. A study of 7 parameters [electrostatic pulse amplitude (A), duration (D) and wavelength (lambda), pump flow rate (P), needle gauge, alginate viscosity and distance between electrodes] showed that P (r = 0.981, p = 0.003) and lambda (r = 0.988, p = 0.0002) were the principal determinants of bead size. To detect potential interactions between parameters, 270 combinations of different levels of A, D, lambda, and P were studied. A multivariate regression analysis of these data confirmed that P and lambda are the prime determinants of bead size, and showed that a 2-parameter (P, lambda) model could be used to precisely predict bead size (R2 = 0.84), while keeping the application simple. The precision of the predictive model is only slightly improved by the use of additional parameters. The reliability of the data used to elaborate this model was demonstrated (p = 0.6226) by comparing them with a second data set obtained under the same conditions. A third set of experiments confirmed the applicability of the model. This work has major implications on the preclinical application of microencapsulation since it showed that it is possible to predetermine the bead size.

To examine 12-month retention rates over 6 years of etanercept patients in Canada, and to identify factors associated with treatment discontinuation. A retrospective cohort study was conducted using longitudinal prescription drug claims data from IQVIA Private Drug Plan database (PDP), Ontario Public Drug Plan database (OPDP), and Régie de l'assurance maladie du Québec database (RAMQ). Between 07/2008 and 06/2010, bio-naïve patients who initiated etanercept were identified and followed for 72 months. Twelve-month retention rates were estimated in one-year increments and factors associated with time to discontinuation over the 72-month period were identified using a Cox proportional hazards regression model. The study identified 4528 etanercept patients (61% female, 85% rheumatic diseases, and 15% psoriasis). Twelve-month etanercept retention rates increased significantly for patients following their first year on therapy (p < 0.0001), with 66% of patients retained at year 1 vs. 79, 82, 84, 83, and 79% at years 2, 3, 4, 5, and 6, respectively. 17.1% (n = 771) of patients were retained for the entire 72-month study. Patients with psoriasis were at increased risk (HR 1.199; p < 0.0001); while public drug coverage plan patients (OPDP HR 0.721; p < 0.0001 and RAMQ HR 0.537; p < 0.0001) were at decreased risk of treatment discontinuation. Twelve-month etanercept retention rates increased significantly for patients following their first year on therapy. Indication and drug coverage plan were associated with patients' time to etanercept discontinuation. With a better understanding of factors associated with retention, programs can be designed to address the specific needs of at-risk groups while supporting patients stable on therapy.

AimsTo determine whether blood glucose test strip (BGTS) utilization in patients with type 2 diabetes (T2D) is associated with the type of diabetes therapy, classified according to hypoglycemic risk.MethodsA retrospective, longitudinal (2006–2012) study of Canadian private drug plans (PDP) and Ontario Public Drug Programs (OPDP) prescription claims was conducted. Analyses were restricted to patients with T2D with or without a claim for BGTS. Daily BGTS utilization (TS/patient/day) was evaluated by diabetes therapy classified by hypoglycemic risk. Multivariate analyses were conducted to identify determinants of BGTS utilization.ResultsThe T2D cohort comprised 5,759,591 observations from 1,949,129 claimants. Mean BGTS utilization was 0.84 TS/patient/day and differed between PDP and OPDP (0.66 vs. 1.00). Daily utilization was greatest in patients receiving therapy associated with a pre-defined high risk of hypoglycemia [insulin: basal + bolus (2.16), premixed (1.65), basal (1.16), other insulin regimens (2.13), and sulfonylureas (0.74)] versus non-sulfonylurea non-insulin-based regimens (0.52). For non-insulin therapy, BGTS utilization was greater for patients on multiple non-insulin therapies versus monotherapy (0.74 vs. 0.53 TS/patient/day). In multivariate analyses, drivers for BGTS utilization included insulin use, previous BGTS use, and female gender. Previous diabetes therapy and duration of therapy were negatively correlated with BGTS utilization.ConclusionsBGTS utilization varies depending on the type of therapy used to treat T2D according to hypoglycemic risk. Decision making regarding BGTS needs to account for robust analyses of current utilization and its value in those settings, including in patients not receiving diabetes therapy and the prevalence of circumstances conducive to more intensive monitoring.

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