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Barbora Kostalova,1 Katerina Mala-Ladova,1 Ales Antonin Kubena,1 Rob Horne,2 Sylvie Dusilova Sulkova,3 Josef Maly1 1Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic; 2Centre for Behavioural Medicine, UCL School of Pharmacy, University College London, London, UK; 3Hemodialysis Centre, University Hospital Hradec Kralove, Hradec Kralove, Czech RepublicCorrespondence: Katerina Mala-LadovaDepartment of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University, Ak. Heyrovskeho 1203/8, Hradec Kralove, 500 05, Czech RepublicTel +420 495 067 486Email ladovaka@faf.cuni.czPurpose: The main aim was to evaluate the changes in beliefs about immunosuppressants over a 3-year period in patients after kidney transplantation. The second aim was to investigate the relationship between beliefs, medication adherence, and selected clinical outcomes such as graft functioning.Patients and Methods: This observational follow-up study was conducted in the outpatient post-transplant clinic at the University Hospital Hradec Kralove in the Czech Republic. Adult patients, at least 4 weeks after kidney transplantation, were invited for the structured interview, which was followed by a self-administered questionnaire survey during their regularly scheduled visits at the clinic. Appropriate paired tests were used to compare two measurements of beliefs about immunosuppressants by BMQ-CZ© in 2016 (baseline) and in 2019 (follow-up). Self-reported adherence was measured by two validated tools (MARS-CZ© and BAASIS©) capturing implementation and discontinuation phases. A generalized linear model was used to investigate the relation between beliefs and the consecutive estimated glomerular filtration rate.Results: The study involved 134 patients. Over time, their perceived treatment necessity beliefs of immunosuppressants decreased, while their treatment-related concerns increased. Overall self-reported non-adherence (ie, taking, dosing and discontinuation of immunosuppressants) was reported by 12% of the patients in both observation periods. In the follow-up period, timing non-adherence was reported by 52 (38.8%) patients. Higher baseline treatment concerns were associated with poor adherence whereas higher baseline treatment necessity beliefs corresponded with better kidney functioning, even after adjusting for age.Conclusion: Higher treatment necessity beliefs corresponded with better kidney functioning, whereas higher treatment concerns were related to non-adherence to immunosuppressants at the beginning of the observed period. Still, most patients accepted their medicines that do not come without risk. Nevertheless, decreasing treatment necessity beliefs on one hand, and increasing treatment concerns on the other, should be considered in clinical practice.Keywords: kidney transplantation, immunosuppressants, treatment necessity beliefs, treatment concerns, medication adherence

Background and objective: Non-adherence to tacrolimus commonly manifests as low drug concentrations and/or high intra-patient variability (IPV) of concentrations across multiple measurements. We aimed to compare several methods of tacrolimus IPV calculation and evaluate how well each reflects blood concentration variation due to medication non-adherence in kidney transplant recipients.Methods: This Czech single-center retrospective longitudinal study was conducted in 2019. All outpatients ≥18 years of age, ≥3 months post-transplant, and on tacrolimus-based regimens were approached. After collecting seven consecutive tacrolimus concentrations we asked participating patients to self-report adherence to immunosuppressants (BAASIS© scale). The IPV of tacrolimus was calculated as the medication level variability index (MLVI), the coefficient of variation (CV), the time-weighted CV, and via nonlinearly modeled dose-corrected trough levels. These patient-level variables were analyzed using regression analysis. Detected nonlinearities in the dose-response curve were controlled for by adding tacrolimus dosing and its higher-order terms as covariates, along with self-reported medication adherence levels.Results: Of 243 patients using tacrolimus, 42% (n = 102) reported medication non-adherence. Non-adherence was associated with higher CVs, higher time-weighted CVs, and lower dose-corrected nonlinearly modeled trough levels; however, it was not associated with MLVIs. All of the significant operationalizations suggested a weak association that was similar across the applied methods.Discussion and conclusion: Implementation non-adherence was reflected by higher CV or time-weighted CV and by lower blood concentrations of tacrolimus. As an additional tool for identifying patients at risk for non-adherence, simple IPV calculations incorporated into medical records should be considered in everyday clinical practice.

Barbora Vankova,1 Katerina Mala-Ladova,1 Ales Antonin Kubena,1 Josef Maly,1 Sylvie Dusilova Sulkova2 1Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic; 2Hemodialysis Centre, University Hospital, Hradec Králové, Czech Republic Purpose: Kidney transplant (KTx) recipients should strictly adhere to their lifelong complex therapeutic regimen, and any barriers to medication adherence can weaken correct patient behavior. This study aimed to determine the adherence to immunosuppressive therapy (IS) in KTx adult outpatients in the Czech Republic, and attempted to gain a greater insight into their attitudes toward IS and self-management tasks.Materials and methods: Pharmacist-led structured interviews were conducted to assess self-reported adherence to IS using the Czech version of the Medication Adherence Report Scale, in the context of attitudes toward IS in terms of necessity and concern scale of the Beliefs about Medicines Questionnaire. A specific questionnaire was developed to target IS self-management tasks. Medication records were also reviewed for IS serum levels, reflecting direct adherence measurement. Descriptive statistics were used to calculate adherence and self-management variables, and were analyzed by univariate and multivariate correlations, including the decision-tree method.Results: The interview was completed by 211 (male 123; mean age 55.0±12.4 years, mean time 6.6±5.9 years after KTx) of the total of 235 patients. Full adherence to IS was reported by 173 (82.0%) patients. Most of them had IS serum levels within the therapeutic range, however, cyclosporine was associated with the highest variability (P