Lut Berben

The Psychometric Properties and Practicability of Self-Report Instruments to Identify Medication Nonadherence in Adult Transplant Patients: A Systematic Review

Introduction. Nonadherence to immunosuppressive therapy is recognized as a key prognostic indicator for poor posttransplantation long-term outcomes. Several methods aiming to measure medication nonadherence have been suggested in the literature. Although combining measurement methods is regarded as the gold standard for measuring nonadherence, self-report is generally considered a central component of adherence assessment. However, no systematic review currently exists to determine which instrument(s) are most appropriate for use in transplant populations. Methodology. The transplant360 Task Force first performed a survey of the self-report adherence instruments currently used in European centers. Next, a systematic literature review of self-report instruments assessing medication adherence in chronically ill patients was conducted. Self-report instruments were evaluated to assess those which were: (a) short and easy to score; (b) assessed both the taking and timing of medication intake; and (c) had established reliability and validity. Results. Fourteen instruments were identified from our survey of European centers, of which the Basel Assessment of Adherence Scale for Immunosuppressives met the aforementioned criteria. The systematic review found 20 self-report instruments, of which only two qualified for use in transplantation, that is, the Brief Antiretroviral Adherence Index and the Medication Adherence Self-Report Inventory. Discussion. The three selected self-report scales may assist transplant professionals in detecting nonadherence. However, these scales were only validated in patients with HIV. Although HIV shares similar characteristics with transplantation, including the importance of taking and timing of medication, further validation in transplant populations is required.

Effect size estimation: Methods and examples

BACKGROUND While the p-value will tell the reader a studys results are statistically significant, it does not provide any information about the practical or clinical importance of the findings. Furthermore, p-values are influenced by sample size. They are more likely to be significant when sample size is large and less likely if the sample is small. Effect size estimates, on the other hand, are not sensitive to sample size and provide information about the direction and strength of the relationship between variables (e.g., a treatment and an outcome). In addition to providing valuable clinical information about study findings, effect size estimates can provide a common metric to compare results across studies. Despite their usefulness, effect size estimates are often not reported as part of the research results. Consequently, effect sizes often have to be calculated based on summary and test statistics reported in research articles. RESULTS This article provides the formulas utilized to directly calculate common effective size estimates using summary statistics reported in research studies, as well as methods to more indirectly estimate these effect sizes when basis summary statistics are not reported. In addition we present formulas to compute the corresponding confidence interval for each effect size.

The spectrum of nonadherence with medication in heart, liver, and lung tranplant patients assessed in various ways

Adherence to medication regimes is crucial for transplant patients. Addressing methodological limitations and gaps in the literature, we studied: (i) the prevalence of nonadherence (NA) with immunosuppression (IS) using various measurement methods, (ii) NA prevalence regarding intake and timing, (iii) changes in NA over time, (iv) differences in NA across organ transplant populations, (v) NA regarding co‐medication. Using a descriptive, prospective, comparative design over 3 months, we included convenience samples of adult heart (n = 79), liver (n = 55), and lung (n = 104) transplant patients. NA with IS was measured using self‐report, collateral report, blood assay, electronic monitoring (Helping HandTM, Bang and Olufsen Medicom, Denmark), and their combinations. In the overall sample, depending on the method used, IS NA ranged from 23.9% to 70.0%. For co‐medication, the overall NA rate was 30.1% using self‐report. Nonadherence rates remained stable over time. At inclusion, significant NA differences between organ groups were reported via self‐ and collateral report; lung transplant patients were less adherent than heart or liver transplant recipients, both to IS and to co‐medication.

Describing the evolution of medication nonadherence from pretransplant until 3 years post-transplant and determining pretransplant medication nonadherence as risk factor for post-transplant nonadherence to immunosuppressives: the Swiss Transplant Cohort Study.

Although medication nonadherence (MNA) is a major risk factor for poor outcomes, the evolution of MNA from pre‐ to 3 years post‐transplant among the four major organ transplant groups remains unknown. Therefore, this study described this evolution and investigated whether pretransplant MNA predicts post‐transplant immunosuppressive medication nonadherence (IMNA). Adult participants (single transplant, pretransplant and ≤1 post‐transplant assessment, using medications pretransplant) in the Swiss Transplant Cohort Study (a prospective nation‐wide cohort study) were included. Nonadherence, defined as any deviation from dosing schedule, was assessed using two self‐report questions pretransplant and at 6, 12, 24 and 36 months post‐transplant. Nonadherence patterns were modelled using generalized estimating equations. The sample included 1505 patients (average age: 52.5 years (SD: 13.1); 36.3% females; 924 renal, 274 liver, 181 lung, 126 heart). The magnitude and variability of self‐reported MNA decreased significantly from pretransplant to 6 months post‐transplant (OR = 0.21; 95% CI: 0.16–0.27). Post‐transplant IMNA increased continuously from 6 months to 3 years post‐transplant (OR = 2.75; 95% CI: 1.97–3.85). Pretransplant MNA was associated with threefold higher odds of post‐transplant IMNA (OR = 3.10; 95% CI: 2.29–4.21). As pretransplant MNA predicted post‐transplant IMNA and a continuous increase in post‐transplant IMNA was observed, early adherence‐supporting interventions are indispensible.

An Ecological Perspective on Medication Adherence

Adherence to a prescribed medication regimen is influenced not only by characteristics of the individual patient, but also by factors within the patient’s environment, or so-called system level factors. Until now, however, health care system factors have received relatively little attention in explaining medication nonadherence. Ecological models might serve as a framework to help explain the influence of health care system factors on patient behavior (e.g., adherence). In an ecological model, different levels of factors influence patients’ behavior, i.e. factors at the patient-level, micro- (provider and social support), meso- (health care organization), and macro (health policy) -levels. In order to understand medication adherence and implement interventions to improve medication adherence, factors at these different levels should be taking into consideration. This paper describes an ecological model compromised of the most important factors at the patient-, micro-, meso- and macro-levels.

Efficacy of a medication adherence enhancing intervention in transplantation: The MAESTRO-Tx trial

BACKGROUND Well-designed randomized controlled trials (RCTs) testing efficacy of post-transplant medication adherence enhancing interventions and clinical outcomes are scarce. METHODS This randomized controlled trial enrolled adult heart, liver, and lung transplant recipients who were >1 year post-transplant and on tacrolimus twice daily (convenience sample) (visit 1). After a 3-month run-in period, patients were randomly assigned 1:1 to intervention group (IG) or control group (CG) (visit 2), followed by a 6-month intervention (visits 2-4) and a 6-month adherence follow-up period (visit 5). All patients used electronic monitoring for 15 months for adherence measurement, generating a daily binary adherence score per patient. Post-intervention 5-year clinical event-free survival (mortality or retransplantation) was evaluated. The IG received staged multicomponent tailored behavioral interventions (visits 2-4) building on social cognitive theory and trans-theoretical model (e.g., electronic monitoring feedback, motivational interviewing). The CG received usual care and attended visits 1-5 only. Intention-to-treat analysis used generalized estimating equation modeling and Kaplan-Meier survival analysis. RESULTS Of 247 patients, 205 were randomly assigned (103 IG, 102 CG). At baseline, average daily proportions of patients with correct dosing (82.6% IG, 78.4% CG) and timing adherence (75.8% IG, 72.2% CG) were comparable. The IG had a 16% higher dosing adherence post-intervention (95.1% IG, 79.1% CG; p < 0.001), resulting in odds of adherence being 5 times higher in the IG than in the CG (odds ratio 5.17, 95% confidence interval 2.86-9.38). This effect was sustained at end of follow-up (similar results for timing adherence). In the IG, 5-year clinical event-free survival was 82.5% vs 72.5% in the CG (p = 0.18). CONCLUSION Our intervention was efficacious in improving adherence and sustainable. Further research should investigate clinical impact, cost-effectiveness, and scalability.

Medication non-adherence as a critical factor in the management of presumed resistant hypertension: a narrative review

AIMS Medication non-adherence is a crucial behavioural risk factor in hypertension management. Forty-three to 65.5% of patients with presumed resistant hypertension are non-adherent. This narrative review focuses on the definition of adherence/non-adherence, measurement of medication adherence, and the management of medication non-adherence in resistant hypertension using multilevel intervention approaches to prevent or remediate non-adherence. METHODS AND RESULTS A review of adherence and resistant hypertension literature was conducted. Medication adherence consists of three different yet related dimensions: initiation, implementation, and discontinuation. To effectively measure medication non-adherence, a combination of direct and indirect methods is optimal. Interventions to tackle medication non-adherence must be integrated in multilevel approaches. Interventions at the patient level can combine educational/cognitive (e.g., patient education), behavioural/counselling (e.g., reducing complexity, cueing, tailoring to patients lifestyle) and psychological/affective (e.g., social support) approaches. Improving provider competencies (e.g., reducing regimen complexity), implementing new care models inspired by principles of chronic illness management, and interventions at the healthcare system level can be combined. CONCLUSIONS Improvement of patient outcomes in presumed resistant hypertension will only be possible if the behavioural dimensions of patient management are fully integrated at all levels.

Building research initiative group: chronic illness management and adherence in transplantation (BRIGHT) study: study protocol

AIM This article describes the rationale, design and methodology of the Building research initiative group: chronic illness management and adherence in transplantation (BRIGHT) study. This study of heart transplant patients will: (1) describe practice patterns relating to chronic illness management; (2) assess prevalence and variability of non-adherence to the treatment regimen; (3) determine the multi-level factors related to immunosuppressive medication non-adherence. BACKGROUND The unaltered long-term prognosis after heart transplantation underscores an urgent need to identify and improve factors related to survival outcomes. The healthcare system (e.g. level of chronic illness management implemented) and patient self-management are major drivers of outcome improvement. DESIGN The study uses a survey design in 40 heart transplant centres covering 11 countries in four continents. METHODS Theoretical frameworks informed variable selection, which are measured by established and investigator-developed instruments. Heart transplant recipients, outpatient clinicians and programmes directors complete a survey. A staged convenience sampling strategy is implemented in heart transplant centres, countries and continents. Depending on the centres size, a random sample of 25-60 patients is selected (N estimated 1680 heart transplant recipients). Five randomly selected clinicians and the medical director from each centre will be invited to participate. CONCLUSION This is the first multi-centre, multi-continental study examining healthcare system and heart transplant centres chronic illness management practice patterns and potential correlates of immunosuppressive medication non-adherence. The knowledge gained will inform clinicians, researchers and healthcare policy makers at which level(s) interventions need to be implemented to improve long-term outcomes for transplant recipients.

Health literacy in heart transplantation: Prevalence, correlates and associations with health behaviors—Findings from the international BRIGHT study

BACKGROUND Health literacy (HL) is a major determinant of health outcomes; however, there are few studies exploring the role of HL among heart transplant recipients. The objectives of this study were to: (1) explore and compare the prevalence of inadequate HL among heart transplant recipients internationally; (2) determine the correlates of HL; and (3) assess the relationship between HL and health-related behaviors. METHODS A secondary analysis was conducted using data of the 1,365 adult patients from the BRIGHT study, an international multicenter, cross-sectional study that surveyed heart transplant recipients across 11 countries and 4 continents. Using the Subjective Health Literacy Screener, inadequate HL was operationalized as being confident in filling out medical forms none/a little/some of the time (HL score of 0 to 2). Correlates of HL were determined using backward stepwise logistic regression. The relationship between HL and the health-related behaviors were examined using hierarchical logistic regression. RESULTS Overall, 33.1% of the heart transplant recipients had inadequate HL. Lower education level (adjusted odds ratio [AOR] 0.24, p < 0.001), unemployment (AOR 0.69, p = 0.012) and country (residing in Brazil, AOR 0.25, p < 0.001) were shown to be associated with inadequate HL. Heart transplant recipients with adequate HL had higher odds of engaging in sufficient physical activity (AOR 1.6, p = 0.016). HL was not significantly associated with the other health behaviors. CONCLUSIONS Clinicians should recognize that almost one third of heart transplant participants have inadequate health literacy. Furthermore, they should adopt communication strategies that could mitigate the potential negative impact of inadequate HL.

Continuous Voxel Classification by Stochastic Relaxation: Theory and Application to MR Imaging and MR Angiography

In this paper we present a stochastic relaxation method based on Bayesian decision theory for voxel classification in medical images. The labels are continuous (as opposed to discrete) values representing the degree of belief that a voxel belongs to a certain object class.