Development and Internal Validation of a Questionnaire Assessing Predisposition to Nonadherence to Immunosuppressive Medication in Kidney Pretransplant Patients.

BACKGROUND: After kidney transplant, nonadherence to immunosuppressive therapy is the main cause of impaired kidney function and graft loss. The objective of this study was the development and internal validation of a clinical questionnaire for assessing the predisposition to adherence to immunosuppressive therapy in kidney pretransplant patients. METHODS: Multicenter prospective study conducted in 7 kidney hemodialysis and 6 kidney transplant centers of 3 Brazilian state capitals. Kidney transplant candidate patients of both sexes and >18-y-old were included. Retransplanted patients were excluded. A 72-item pilot version of the questionnaire, created through literature review complemented with a focus group of 8 kidney pretransplant patients, was administered to 541 kidney transplant candidate patients. Factor analysis with varimax rotation was used for questionnaire development. Internal validity evaluation used Cronbach's alpha and test-retest reliability. Construct validity was assessed by differentiation by known groups. RESULTS: The final questionnaire, named Kidney AlloTransplant Immunosuppressive Therapy Adherence (KATITA) Questionnaire, consisting of 25 items in 3 dimensions, presented good internal consistency reliability (Cronbach's alpha 0.81). The 3 dimensions and respective Cronbach's alpha were "Carelessness" (14 items, 0.81), "Skepticism" (6 items, 0.57), and "Concern" (5 items, 0.62). The interdimension correlation matrix showed low correlation coefficients (<0.35). Test-retest reliability, evaluated with 154 patients, showed an intraclass correlation coefficient of 0.62 (moderate agreement). The scale showed construct validity. CONCLUSIONS: The KATITA-25 questionnaire is the first psychometric instrument for evaluation of predisposition to nonadherence to immunosuppressive medication in candidate patients for kidney transplant in the pretransplant setting.

Combining amorphous solid dispersions for improved kinetic solubility of posaconazole simultaneously released from soluble PVP/VA64 and an insoluble ammonio methacrylate copolymer.

The aim of this study was to evaluate the potential of combining multiple ASDs based on water soluble and insoluble polymers to reach and maintain poorly soluble posaconazole (PCZ) supersaturation over time. ASDs of PCZ were obtained with PVP/VA64 or an ammonio methacrylate copolymer by solvent evaporation method with a fixed 20% (wt/wt%) drug loading ratio and physical mixtures of these ASDs were prepared at various proportions. ASDs were characterized by Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD) and compared to their respective physical mixture with crystalline PCZ. Crystalline PCZ equilibrium solubility was determined at pH 1.2-2 range. Dissolution profiles were constructed under non-sink condition with an adapted dissolution system. PXRD analysis demonstrated that both ASDs were at the amorphous state and FT-IR spectroscopy revealed that the analytical signal of PCZ was also absent in both ASDs. Equilibrium solubility of crystalline PCZ varied between 26.36 ±â€¯0.32 (pH 2) to 609.33 ±â€¯3.68 (pH 1.2) µg/mL. All ASDs reached higher concentrations than the equilibrium solubility of crystalline PCZ during dissolution. PVP/VA64 ASDs showed dominance over PCZ dissolution and recrystallization rates whereas Eudragit RS PO ASD alone did not cause PCZ recrystallization whatsoever. The combination containing 20 mg PVP/VA64 + 80 mg Eudragit RS PO as PCZ carriers obtained the highest AUC, suggesting that even after the PVP/VA64 part was completely dissolved, reaching a concentration above crystalline PC Cs, the insoluble polymer could still release PCZ slowly and maintain supersaturation over time. The research demonstrated a potential of combining multiple ASDs to achieve distinct dissolution profiles while increasing the kinetic solubility of poorly soluble drugs.