Comparison of different methods to assess tacrolimus concentration intra-patient variability as potential marker of medication non-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

Reimbursed medication adherence enhancing interventions in 12 european countries:Current state of the art and future challenges

Background: Medication non-adherence jeopardises the effectiveness of chronic therapies and negatively affects financial sustainability of healthcare systems. Available medication adherence-enhancing interventions (MAEIs) are utilised infrequently, and even more rarely reimbursed. The aim of this paper was to review reimbursed MAEIs across selected European countries. Methods: Data on reimbursed MAEIs were collected from European countries at the ENABLE Cost Action expert meeting in September 2021. The identified MAEIs were analysed and clustered according to their characteristics, direct vs. indirect relation to adherence, and the targeted adherence phase. Results: Out of 12 contributing countries, 10 reported reimbursed MAEIs, 28 in total, of which 20 were identified as MAEIs targeting adherence directly. Reimbursed MAEIs were most often performed by either doctors (n = 6), nurses (n = 6), or pharmacists (n = 3). The most common types of MAEIs were education (n = 6), medication regimen management (n = 5), and adherence monitoring feedback (n = 4). Only seven reimbursed MAEIs were technology-mediated, whereas 11 addressed two interlinked phases of medication adherence, i.e., implementation and persistence. Conclusion: Our review highlights the scarcity of reimbursed MAEIs across the selected European countries, and calls for their more frequent use and reimbursement

Awareness campaigns of atrial fibrillation as an opportunity for early detection by pharmacists: an international cross-sectional study

Atrial fibrillation (AF) accounts for up to one third of strokes, one of the lead mortality causes worldwide. The European Society of Cardiology guidelines recommend opportunistic screening as a means to increase the odds of early detection and institution of appropriate treatment according to risk factors identified. However, in most countries there are various barriers to effective uptake of screening, including low awareness. The Atrial Fibrillation Association is a patient association engaged with raising awareness of AF. Establishing a partnership with the International Pharmacists for Anticoagulation Care Taskforce, we set as goals to test a model for raising awareness of AF involving pharmacists globally; and to identify barriers and enablers to its implementation. A cross-sectional study was conducted during the Arrhythmia Alliance World Heart Rhythm Week. Pharmacists from 10 countries invited individuals (≥ 40 years; without anticoagulation therapy of AF) to participate in the awareness campaign. Participants agreeing were engaged in the early detection of AF (EDAF) using pulse palpation. Individuals with rhythm discrepancies were referred and prospectively assessed to have information on the proportion of confirmed diagnosis, leading to estimate the detection rate. Interviews with country coordinators explored barriers and enablers to implementation. The study involved 4193 participants in the awareness campaign and 2762 in the EDAF event (mean age 65.3 ± 13.0), of whom 46.2% individuals were asymptomatic, recruited across 120 sites. Most common CHA2DS2-VASc risk factor was hypertension. Among 161 patients referred to physician, feedback was obtained for 32 cases, of whom 12 new arrhythmia diagnoses were confirmed (5 for AF, 2 for atrial flutter), all among elders (≥ 65 years). Qualitative evaluation suggested a local champion to enable pharmacists’ success; technology enhanced engagement amongst patients and increased pharmacists’ confidence in referring to physicians; interprofessional relationship was crucial in success. This study suggests pharmacists can contribute to greater outreach of awareness campaigns. Effective communication pathways for inter-professional collaboration were suggested enablers to gain full benefits of EDAF

Inflammatory blood parameters as prognostic factors for implant-associated infection after primary total hip or knee arthroplasty: a systematic review

Abstract Background Implant-associated infection (IAI) is a potential complication following total hip (THA) or knee arthroplasty (TKA). The initial phase of the inflammatory process can be measured by applying one of the inflammatory blood parameters (IBP). This systematic review aims to assess the response of IBP to trauma caused by orthopedic surgery and evaluate the clinical utility of quantitative measurements of IBP as prognostic factors for infection. Methods All studies indexed in Ovid MEDLINE (PubMed), Ovid EMBASE, the Cochrane Library and the ISI Web of Science databases, from inception until January 31, 2020, were analyzed. Studies included were those on adults who underwent THA or TKA with minimum follow up of 30 days after surgery. In addition to minimum follow up, data on the prognostic factors for pre- or post-THA/TKA IAI were mandatory. The Quality Assessment of Diagnostic Accuracy tool (version 2) (QUADAS-2) and Standards for Reporting of Diagnostic Accuracy Studies guideline 2015 (STARD) were used for quality assessment. Results Twelve studies fulfilled the inclusion and exclusion criteria. C-reactive protein was analyzed in seven studies, interleukin-6 in two studies and erythrocyte sedimentation rate in eight studies. White blood cell count and procalcitonin were analyzed in the only study. The overall quality of included studies was low. A potential for other cytokines (IL-1ra, IL-8) or MCP-1 was observed. Conclusions This is the first systematic review of IBP response to orthopedic surgery which identified some IBP for pre/post-operative screening, despite insufficient data supporting their prognostic potential for patient risk stratification

Medication adherence interventions in transplantation lack information on how to implement findings from randomized controlled trials in real-world settings: A systematic review

Growing numbers of randomized controlled trials (RCTs) are showing the effectiveness of interventions to improve medication adherence in transplantation recipients. However, real-world implementation is still a major challenge. This systematic review assesses the range of information available in RCTs supporting these interventions' clinical adoption in adult transplant populations.; We included RCTs of interventions that a) targeted any phase of medication adherence in solid organ or allogeneic stem cell transplantation recipients and b) were published between January 2015 and November 2020. We excluded study protocols, conference abstracts and studies focusing only on pediatric populations. We identified relevant database and trial registries as well as traced references backward and citations forward. Implementation-relevant information was evaluated using adapted versions of Peters' ten criteria: 1. healthcare/organizational context; 2. social/economic/policy context; 3. patient involvement; 4. other stakeholder involvement; 5. sample representativeness; 6. trial conducted in a real-world-setting; 7. presence of feasibility study; 8. implementation strategy; 9. process evaluation; 10. implementation outcomes, using a stoplight color-rating system.; Screening 17'004 titles/abstracts resulted in 23 eligible RCTs, including 2'339 patients (n = 19-209/study). All included studies focused on the implementation phase of medication adherence. The best-reported criteria were feasibility study (43%), representative sample (17%) and conducted in a real-world-setting (17%). Least reported were context (9%), implementation strategies (4%), process evaluation (4%).; RCTs testing medication adherence interventions tend to report limited implementation-relevant information. This hinders their translation to real-world transplant settings. Integrating implementation science principles early in the conceptualization of RCTs would fuel real-world-translation, reducing research waste