Rima Kregždytė

Comparison of the pharmacokinetic and pharmacodynamic properties of two recombinant granulocyte colony-stimulating factor formulations after single subcutaneous administration to healthy volunteers

BACKGROUND AND OBJECTIVE The aim of this randomized, single dose, two-period crossover study with two weeks wash-out period was the demonstration of bioequivalence of two recombinant human granulocyte colony-stimulating factor (rG-CSF) formulations after subcutaneous administration of 300μg comparing their pharmacokinetic (primary endpoints AUC0-24, AUC0-∞ and Cmax) and pharmacodynamic (primary endpoints ANC AUC0-72, ANC AUC0-∞ and ANCmax) profiles in healthy male subjects. MATERIALS AND METHODS A total of 36 (23.0±6.0 years, 76.6±7.2kg) healthy subjects were recruited. Using a 1:1 randomization ratio, subjects were randomly assigned to one of two possible treatment-sequence groups to receive the single dose of test formulation (Gp-02) and reference product (Neupogen™) concentrations were measured by enzyme-linked immunosorbent assay (ELISA) up to 24h and the Absolute Neutrophil Count (ANC) was determined using hematology analyzer Coulter STKS™ (Beckman Coulter) up to 72h after injection. The geometric mean of primary pharmacokinetic and pharmacodynamic variables were considered bioequivalent if the 90% confidence intervals (CI) would fall in the bioequivalence range of 80%-125%. RESULTS AUC0-24 (ratio of means 103.4, 90% CI: 95.6-111.9), AUC0-∞ (103.4, 90% CI: 95.7-111.7), Cmax (99.6, 90% CI: 89.0-111.4), ANC AUC0-72 (100.0, 90% CI: 96.6-103.5), ANC AUC0-∞ (100.8, 90% CI: 96.5-105.3), and ANCmax (100.2, 90% CI: 95.4-105.1) were determined. Single doses of test and reference formulations were well tolerated. The incidence of AEs was equally distributed across treatment groups with the most frequent AEs being headache, fever, and back pain. CONCLUSIONS The study results demonstrated the bioequivalence of Gp-02, a new formulation of filgrastim, and the reference product Neupogen™.

The cost of newly diagnosed breast cancer in Lithuania, 2011.

BACKGROUND AND OBJECTIVE Although the cost of treating women with breast cancer (BC) is an important component for cost saving and effectiveness in relation to the benefits of BC treatment interventions, there is limited information on the direct cost reported for BC in Lithuania. Therefore the aim of this study was to evaluate annual direct medical cost for newly diagnosed BC in Lithuania in the year 2011. MATERIALS AND METHODS The retrospective incidence-based top-down direct cost analysis was used. From January 1 to December 31, 2011 incident cases of BC (N=1142) registered by the National Health Insurance Fund, the stage determined by Lithuanian Cancer Registry were included in the study. RESULTS The total average direct cost of BC amounted per patient was 2580 (95% CI 2444-2752)EUR in 2011. The main cost driver per BC patients was the inpatient hospital stay, respectively 1655 (95% CI 1478-2334)EUR. The average outpatient cost for one BC patient was 564 (95% CI 547-898)EUR. The dominant proportion of inpatient expenditures was assigned to BC surgery and chemotherapy treatment. The BC direct medical cost increased according to the diagnosed stage of diseases from 2409 (95% CI 2196-2621)EUR in stage 1 to 3688 (95% CI 2703-4672)EUR in stage 4. The direct medical cost was inversely proportional to age. CONCLUSIONS The direct BC medical cost estimates provided by this analysis can be used to determine priorities for the future research on BC treatment interventions.

Validation of the EFFECT questionnaire for competence-based clinical teaching in residency training in Lithuania

BACKGROUND AND AIM In 2013, all residency programs at the Lithuanian University of Health Sciences were renewed into a competency-based medical education curriculum. To assess the quality of clinical teaching in residency training, we chose the EFFECT (evaluation and feedback for effective clinical teaching) questionnaire designed and validated at the Radboud University Medical Centre in the Netherlands. The aim of this study was to validate the EFFECT questionnaire for quality assessment of clinical teaching in residency training. MATERIALS AND METHODS The research was conducted as an online survey using the questionnaire containing 58 items in 7 domains. The questionnaire was double-translated into Lithuanian. It was sent to 182 residents of 7 residency programs (anesthesiology reanimathology, cardiology, dermatovenerology, emergency medicine, neurology, obstetrics and gynecology, physical medicine and rehabilitation). Overall, 333 questionnaires about 146 clinical teachers were filled in. To determine the item characteristics and internal consistency (Cronbachs α), the item and reliability analyses were performed. Furthermore, confirmatory factor analysis (CFI) was performed using a model for maximum-likelihood estimation. RESULTS Cronbachs α within different domains ranged between 0.91 and 0.97 and was comparable with the original version of the questionnaire. Confirmatory factor analysis demonstrated satisfactory model-fit with CFI of 0.841 and absolute model-fit RMSEA of 0.098. CONCLUSIONS The results suggest that the Lithuanian version of the EFFECT maintains its original validity and may serve as a valid instrument for quality assessment of clinical teaching in competency-based residency training in Lithuania.