Motivational interviewing to support medication adherence in older patients: Barriers and facilitators for implementing in hospital setting according to healthcare professionals.

OBJECTIVE: The aim of this study was to understand through Healthcare professionals' (HCPs) opinions the barriers and facilitators to implement MI in older hospitalized patients. METHODS: A qualitative study with semi-structured interviews was performed among 23 HCPs involved in the medication management of older hospitalized patients (geriatricians, nurses, psychologists and pharmacists). A thematic analysis was conducted using a deductive approach through the Theoretical Domain Framework (TDF), and an inductive approach. RESULTS: The thematic analysis reported 25 factors influencing MI implementation, mapped into 8 TDF themes, and including 13 facilitators, 8 barriers, and 4 both. The main factors identified were: 'cognitive and sensory disorders' (barrier), 'having dedicated time and HCPs' (facilitator and barrier), and the 'HCP's awareness about MI' (facilitator). Ten factors were identified as specific to the older population. CONCLUSIONS: Implementing MI in a hospital setting with older patients presented both barriers and facilitators. PRACTICE IMPLICATIONS: To ensure successful MI implementation, it is important to take into account the older patients' context, the hospital environment, and the HCPs-related factors.

The differential impact of a 6-versus 12-month pharmacist-led interprofessional medication adherence program on medication adherence in patients with diabetic kidney disease: the randomized PANDIA-IRIS study.

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention. Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases. Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons. Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.

[Diabetic nephropathy: Interprofessional support of medication adherence]. / Néphropathie diabétique : soutenir l'adhésion médicamenteuse de façon interprofessionnelle.

Medication non-adherence in patients with diabetic kidney disease (DKD) is endemic. The PANDIA-IRIS study, implemented at the community pharmacy of Unisanté, illustrates the support of medication adherence in patients with DKD by pharmacists, through an interprofessional program (IMAP) based on a behavioral science theoretical framework. Implementing behavioural support programmes such as PANDIA-IRIS on a large scale in Switzerland is both a necessity and a challenge. These programmes should be an integral part of standard patient care. The transition of care towards interprofessional collaborations and a clarification of roles in supporting adherence, including the patient as a partner, will contribute to fully considering adherence in therapeutic decision making and support to enable better achievement of long-term clinical goals.

La non-adhésion médicamenteuse chez les patient-es avec une néphropathie diabétique (ND) est endémique. L'étude PANDIA-IRIS, implémentée à la pharmacie communautaire d'Unisanté, illustre le soutien de l'adhésion des patient-es avec ND par des pharmacien-nes, au travers d'un programme interprofessionnel (IMAP) fondé sur un cadre théorique des sciences du comportement. Mettre en place des programmes d'accompagnement comportemental comme PANDIA-IRIS à large échelle en Suisse est à la fois une nécessité et un défi. Ces programmes devraient faire partie intégrante des soins standards des patient-es. La transition des soins vers des collaborations interprofessionnelles et une clarification des rôles dans le soutien de l'adhésion, incluant le-la patient-e comme partenaire, contribueront à considérer pleinement l'adhésion dans la prise de décisions thérapeutiques et dans son accompagnement pour permettre une meilleure atteinte des objectifs cliniques à long terme.

[The prescription: messenger between the person, the doctor's office, the nursing and pharmacy teams]. / L'ordonnance : messager entre la personne, le cabinet médical, l'équipe infirmière et la pharmacie. Introduction à la collaboration interprofessionnelle.

Interprofessional collaboration is essential to enhance quality of care and patient safety. It is clearly defined and requires the following 6 competencies: role clarification, teamwork, interprofessional conflict resolution, collaborative leadership, interprofessional communication and patient/client/family/community-centered care. Through different variations of a clinical scenario in primary care, we propose to demonstrate the importance of putting these skills into practice and to analyze the opportunities to reflect on the different types of interprofessional interactions depending on the complexity of the situation.

La collaboration interprofessionnelle est essentielle pour renforcer la qualité des soins et la sécurité des patient-e-s. Elle est clairement définie et requiert les 6 compétences suivantes : la clarification des rôles et des besoins de chacun, le travail d'équipe, la résolution des conflits, le leadership collaboratif, la communication interprofessionnelle et les soins centrés sur la personne, ses proches et la communauté. À travers différentes variantes d'un scénario clinique en soins primaires, nous proposons de démontrer l'importance d'utiliser ces compétences et d'analyser les opportunités de réfléchir aux différents types d'interactions interprofessionnelles en fonction de la complexité de la situation.

[Learning motivational interviewing to better support patient medication adherence]. / Se former à l'entretien motivationnel pour mieux soutenir l'adhésion thérapeutique des patients.

Motivational interviewing (MI), developed in the 1980s, demonstrated efficacy in helping patients to change their health behavior, and more recently in supporting patient therapeutic adherence. However, the training in patient therapeutic adherence support is poor and unequally distributed within the initial and continuing training of health professionals. To cope, an interprofessional continuing training was designed by health professionals and researchers, aiming at acquiring fundamental knowledge in therapeutic adherence and MI skills. The results of the first training session should encourage health professionals to train, and decision-makers to promote wider dissemination of this training.

Depuis son développement dans les années 1980, l'entretien motivationnel (EM) s'est avéré efficace pour accompagner les patients à modifier leur comportement en santé, et plus récemment dans le soutien de leur adhésion thérapeutique. Cependant, la formation au soutien de l'adhésion thérapeutique est pauvre et inégalement répartie au sein de la formation initiale et continue des professionnels de santé. Face à ce constat, une formation continue interprofessionnelle a été conçue par des professionnels de santé et chercheur-e-s, visant à l'acquisition des connaissances fondamentales en adhésion thérapeutique et des compétences en EM. Les résultats objectivés par la première session de formation devraient inciter les professionnels de santé à se former et les décideurs à favoriser une diffusion plus large de ce type de formation.

Building Interprofessional Collaborative Practices Through a Support Program for Patients With Type 2 Diabetes in Primary Care.

INTRODUCTION: The building of interprofessional collaborative practices throughout the implementation process of a patient support program (Siscare) in primary care for patients with type 2 diabetes was assessed. Siscare included regular patient-pharmacist motivational-based interviews; medication adherence, patient-reported, and clinical outcomes monitoring; and physician-pharmacist interactions. METHOD: This investigation was a prospective, multicenter, observational, mixed-methods cohort study. Interprofessionality was operationalized through four progressive levels of interrelationship practices between the health care professionals. The target number of patients per pharmacy was 10 among 20 pharmacies. RESULTS: The project started with the recognition of Siscare by stakeholders, the creation of an interprofessional steering committee, and the adoption of Siscare by 41 pharmacies among 47 pharmacies in April 2016. Nineteen pharmacies presented Siscare at 43 meetings attended by 115 physicians. Twenty-seven pharmacies included 212 patients; however, no physician prescribed Siscare. Collaboration primarily occurred through the unidirectional transmission of information from the pharmacist to the physician (level 1: 70% of pharmacists transmitted interview reports to physicians), bidirectional exchange of information sometimes occurred (level 2: 42% received physician responses), and concerted measures of treatment objectives took place occasionally (level 3). Twenty-nine of 33 physicians surveyed were in favor of this collaboration. DISCUSSION: Despite multiple implementation strategies, physician resistance and lack of motivation to participate exists, but Siscare was well received by pharmacists, patients, and physicians. Barriers to collaborative practice (financial and IT) need to be further explored. Interprofessional collaboration is a clear need to improve type 2 diabetes adherence and outcomes.

Effectiveness of an Interprofessional Program (Siscare) for Supporting Patients With Type 2 Diabetes.

Objective: To assess the effectiveness of an interprofessional support program (Siscare) that includes motivational interviews (patient-pharmacist), electronic monitoring (EM) of medications, patient-reported and clinical outcomes monitoring, and interactions with physicians for patients with type 2 diabetes in French-speaking Switzerland. Methods: This was a prospective, multicenter, observational cohort study using a hybrid implementation-effectiveness design. Individual daily adherence to at least one oral antidiabetic medication was measured by EM. A global adherence score was estimated by the product of a model-estimated implementation and a nonparametric estimate of persistence over time. Clinical outcomes (A1C, blood glucose, BMI, blood pressure, heart rate, and cholesterol levels) and quality of life (QoL) were analyzed over time using linear mixed-effect models. Results: A total of 212 patients were included from 27 pharmacies; 120 patients (57%) were followed up for at least 15 months. In total, 140 patients (66%) were male, the mean age was 64 ± 11 years, and the mean number of chronic medications per patient at baseline was 5 ± 3. Of 178 patients who used EM, 95% (95% CI 92-99%) remained persistent at the end of the follow-up period. The percentage of persistent patients taking their medications appropriately (implementation) was stable during follow-up and was estimated to be 90% (95% CI 87-92%) at baseline and 88% (95% CI 84-91%) at month 15. At baseline, the mean A1C and BMI were 7.5% and 31 kg/m2, respectively, which decreased by 0.5% (P = 0.012) and 0.6 kg/m2 (P = 0.017), respectively, after 15 months. QoL remained stable during follow-up. Conclusion: The program supports medication adherence and improves clinical outcomes, illustrating the overall preventive effect of coordinated care.

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.

Motivational interviewing to support medication adherence in adults with chronic conditions: Systematic review of randomized controlled trials.

OBJECTIVES: To systematically review published randomized controlled trials (RCTs) assessing the efficacy of MI to support medication adherence in adults with chronic conditions. METHODS: A systematic review (PROSPERO-CRD42020025374) was performed by searching in Pubmed/MEDLINE, PsycINFO, The Cochrane Library and Web of Science. Studies were included for the following: RCTs assessing the impact of MI on medication adherence among adults with chronic diseases. Two reviewers conducted independent screening of records and full-text articles published until July 2020. Quality was assessed with the Risk of Bias 2 tool for RCTs. RESULTS: From 1262 records identified, 54 RCTs were included. The MI interventions were delivered alone or in combination with other interventions, and varied in mode of delivery (e.g. face-to-face, phone), exposure level (duration, number of sessions), and provider characteristics (profession, training). Most interventions were developed in infectious diseases (n = 16), cardiology (n = 14), psychiatry (n = 8), and endocrinology (n = 7). Medication adherence showed significant improvement in 23 RCTs, and other clinical outcomes were improved in 19 RCTs (e.g. risky behaviors, disease symptoms). CONCLUSIONS: MI is an approach to medication adherence support with an increasing evidence base in several clinical domains and further potential for adaptation to different settings. PRACTICE IMPLICATIONS: In further studies, particular attention should focus on methodological issues such as the populations of patients to include - patients with suboptimal adherence, the evaluation of fidelity to the MI spirit and components, and a sound measurement of medication adherence and clinical outcomes.

Population Pharmacokinetics of Palbociclib and Its Correlation with Clinical Efficacy and Safety in Patients with Advanced Breast Cancer.

Neutropenia is the most frequent dose-limiting toxicity reported in patients with metastatic breast cancer receiving palbociclib. The objective of this study was to investigate the pharmacokinetic-pharmacodynamic (PK/PD) relationships for toxicity (i.e., absolute neutrophil count, ANC) and efficacy (i.e., progression-free survival, PFS). A semi-mechanistic PK/PD model was used to predict neutrophils' time course using a population approach (NONMEM). Influence of demographic and clinical characteristics was evaluated. Cox proportional hazards models were developed to evaluate the influence of palbociclib PK on PFS. A two-compartment model with first-order absorption and a lag time adequately described the 255 palbociclib concentrations provided by 44 patients. The effect of the co-administration of proton-pump inhibitors in fasting conditions increased palbociclib clearance by 56%. None of the tested covariates affected the PD parameters. Model-based simulations confirmed the concentration-dependent and non-cumulative properties of palbociclib-induced neutropenia, reversible after treatment withdrawal. The ANC nadir occurred approximately at day 24 of each cycle. Cox analyses revealed a trend for better PFS with increasing palbociclib exposure in older patients. By characterizing palbociclib-induced neutropenia, this model offers support to clinicians to rationally optimize treatment management through patient-individualized strategies.

Forgiveness of Dolutegravir-Based Triple Therapy Compared With Older Antiretroviral Regimens: A Prospective Multicenter Cohort of Adherence Patterns and HIV-RNA Replication.

BACKGROUND: For many people with HIV (PWH), taking antiretroviral therapy (ARV) every day is difficult. METHODS: Average adherence (Av-Adh) and log-transformed treatment interruption (TI) to ARV were prospectively measured over 6 months using electronic drug monitoring (EDM) in several cohorts of PWH. Multivariate linear regression models including baseline confounders explored the influence of EDM-defined adherence (R 2) on 6-month log10 HIV-RNA. Multivariate logistic regression models were used to compare the risk of HIV-RNA detection (VR) within subgroups stratified by lower (≤95%) and higher (>95%) Av-Adh. RESULTS: Three hundred ninety-nine PWH were analyzed with different ARVs: dolutegravir (n = 102), raltegravir (n = 90), boosted PI (bPI; n = 107), and NNRTI (n = 100). In the dolutegravir group, the influence of adherence pattern measures on R 2 for HIV-RNA levels was marginal (+2%). Av-Adh, TI, and Av-Adh × TI increased the R 2 for HIV-RNA levels by 54% and 40% in the raltegravir and bPI treatment groups, respectively. TI increased the R 2 for HIV-RNA levels by 36% in the NNRTI treatment group. Compared with the dolutegravir-based regimen, the risk of VR was significantly increased for raltegravir (adjusted odds ratio [aOR], 45.6; 95% CI, 4.5-462.1; P = .001), NNRTIs (aOR, 24.8; 95% CI, 2.7-228.4; P = .005), and bPIs (aOR, 28.3; 95% CI, 3.4-239.4; P = .002) in PWH with Av-Adh ≤95%. Among PWH with >95% Av-Adh, there were no significant differences in the risk of VR among the different ARVs. CONCLUSIONS: These findings support the concept that dolutegravir in combination with 2 other active ARVs achieves greater virological suppression than older ARVs, including raltegravir, NNRTI, and bPI, among PWH with lower adherence.

Optimizing Oral Targeted Anticancer Therapies Study for Patients With Solid Cancer: Protocol for a Randomized Controlled Medication Adherence Program Along With Systematic Collection and Modeling of Pharmacokinetic and Pharmacodynamic Data.

BACKGROUND: The strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response. OBJECTIVE: The aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations. METHODS: The OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits. RESULTS: The first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022. CONCLUSIONS: The OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients' needs and to consider their concerns about their PKI self-management, considering the patient as an active partner. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484064; https://clinicaltrials.gov/ct2/show/NCT04484064. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30090.

[Hospital to home transition of care: challenges for patients with type 2 diabetes]. / Transition hôpital-ambulatoire : les enjeux pour les patients avec un diabète sucré.

The transition from hospital to ambulatory care is a high-risk period for patients with diabetes mellitus and is a challenge for health care professionals. Various interprofessional collaborative interventions have shown a positive impact on continuity of care at discharge. Communication and transmission of information between the hospital and ambulatory settings as well as coordination between healthcare professionals are key points to explore and to improve to ensure optimal continuity of care.

La transition entre l'hôpital et l'ambulatoire est une période à risque pour les patients avec un diabète sucré et un enjeu pour les professionnels de la santé. Différentes interventions en collaboration interprofessionnelle ont montré un impact positif sur la continuité des soins à la sortie de l'hôpital. La communication et la transmission d'informations entre les milieux hospitalier et ambulatoire ainsi qu'une coordination entre les professionnels de la santé sont des points clés à explorer et à continuer d'améliorer pour garantir une continuité des soins optimale.

Interprofessional Medication Adherence Program for Patients With Diabetic Kidney Disease: Protocol for a Randomized Controlled and Qualitative Study (PANDIA-IRIS).

BACKGROUND: Despite effective treatments, more than 30% of patients with diabetes will present with diabetic kidney disease (DKD) at some point. Patients with DKD are among the most complex as their care is multifactorial and involves different groups of health care providers. Suboptimal adherence to polypharmacy is frequent and contributes to poor outcomes. As self-management is one of the keys to clinical success, structured medication adherence programs are crucial. The PANDIA-IRIS (patients diabétiques et insuffisants rénaux: un programme interdisciplinaire de soutien à l'adhésion thérapeutique) study is based on a routine medication adherence program led by pharmacists. OBJECTIVE: The aim of this study is to define the impact of the duration of this medication adherence program on long-term adherence and clinical outcomes in patients with DKD. METHODS: This monocentric adherence program consists of short, repeated motivational interviews focused on patients' medication behaviors combined with the use of electronic monitors containing patients' medications. When patients open the electronic monitor cap to take their medication, the date and hour at each opening are registered. In total, 73 patients are randomized as 1:1 in 2 parallel groups; the adherence program will last 6 months in the first group versus 12 months in the second group. After the intervention phases, patients continue using their electronic monitors for a total of 24 months but without receiving feedback. Electronic monitors and pill counts are used to assess medication adherence. Persistence and implementation will be described using Kaplan-Meier curves and generalized estimating equation multimodeling, respectively. Longitudinal adherence will be presented as the product of persistence and implementation and modelized by generalized estimating equation multimodeling. The evolution of the ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified-Release Controlled Evaluation) and UKPDS (United Kingdom Prospective Diabetes Study) clinical scores based on medication adherence will be analyzed with generalized estimating equation multimodeling. Patients' satisfaction with this study will be assessed through qualitative interviews, which will be transcribed verbatim, coded, and analyzed for the main themes. RESULTS: This study was approved by the local ethics committee (Vaud, Switzerland) in November 2015. Since then, 2 amendments to the protocol have been approved in June 2017 and October 2019. Patients' recruitment began in April 2016 and ended in October 2020. This study was introduced to all consecutive eligible patients (n=275). Among them, 73 accepted to participate (26.5%) and 202 (73.5%) refused. Data collection is ongoing and data analysis is planned for 2022. CONCLUSIONS: The PANDIA-IRIS study will provide crucial information about the impact of the medication adherence program on the adherence and clinical outcomes of patients with DKD. Monitoring medication adherence during the postintervention phase is innovative and will shed light on the duration of the intervention on medication adherence. TRIAL REGISTRATION: Clinicaltrials.gov NCT04190251_PANDIA IRIS; https://clinicaltrials.gov/ct2/show/NCT04190251. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25966.

Association of Incomplete Adherence to Antiretroviral Therapy With Cardiovascular Events and Mortality in Virologically Suppressed Persons With HIV: The Swiss HIV Cohort Study.

BACKGROUND: Incomplete antiretroviral therapy (ART) adherence, even if sufficient to maintain viral suppression, is associated with enhanced inflammation in persons with HIV (PWH). However, its clinical implications remain unknown. METHODS: PWH enrolled in the Swiss HIV Cohort Study without a history of cardiovascular disease (CVD) who initiated ART between 2003 and 2018 and had viral suppression (<50 copies/mL) for ≥6 months were evaluated. The association between incomplete self-reported ART adherence (≥1 or ≥2 missed doses in the last month) and (1) any CVD event (myocardial infarction, revascularization, cerebral hemorrhage, stroke, and/or death due to CVD event) or (2) non-CVD-related death was evaluated using adjusted Cox proportional hazards models. RESULTS: A total of 6971 PWH (74% male) were included in the analysis (median age [interquartile range {IQR}], 39 [32-47] years). The median (IQR) follow-up was 8 (4-11) years, with 14 (8-23) adherence questionnaires collected per participant. In total, 205 (3%) participants experienced a CVD event, and 186 (3%) died a non-CVD-related death. In an adjusted competing risk model where missing data were imputed, missing ≥1 ART dose showed an increased, but not statistically significant, risk for CVD events (hazard ratio [HR], 1.23; 95% CI, 0.85-1.79; P = .28). Non-CVD-related mortality showed a statistically significantly increased risk with missing ≥1 ART dose (HR, 1.44; 95% CI, 1.00-2.07; P = .05) and missing ≥2 ART doses (HR, 2.21; 95% CI, 1.37-3.57; P = .001). CONCLUSIONS: Incomplete ART adherence was significantly associated with an increased risk for non-CVD-related mortality in PWH with virologic suppression. This highlights the potential role of nonadherence to ART as a driver of non-AIDS clinical outcomes.

Longitudinal analysis of safety and medication adherence of patients in the Fingolimod patient support program: a real-world observational study.

The Fingolimod Patient Support Program (F-PSP) is an interprofessional specialty pharmacy service designed to ensure responsible use of fingolimod by promoting patient safety and medication adherence. This study aims to evaluate the safety and medication adherence of patients who joined the F-PSP between 2013 and 2016. Sociodemographic and medical characteristics, patient safety data (patient-reported symptoms, discontinuations due to adverse events (AEs), repeated first-dose monitoring), and medication adherence (implementation, persistence, reasons for discontinuation, influence of covariates, barriers and facilitators) were described. Sixty-seven patients joined the F-PSP. Patients reported a high frequency of symptoms. Due to AEs, 7 patients discontinued fingolimod, 3 took therapeutic breaks, and 1 reduced the regimen temporarily. Three patients repeated the first-dose monitoring. Patients had a high medication adherence over the 18-month analysis period: implementation decreased from 98.8 to 93.7%, and fingolimod persistence was 83.2% at 18 months. The patients' level of education, professional situation, and living with child(ren) influenced implementation. Patients reported more facilitators of medication adherence than barriers. The F-PSP seems valuable for supporting individual patients (ensuring responsible use of fingolimod and inviting patients for shared-decision making) and public health (indirectly gathering real-world evidence).

Random forest machine learning algorithm predicts virologic outcomes among HIV infected adults in Lausanne, Switzerland using electronically monitored combined antiretroviral treatment adherence.

Machine Learning (ML) can improve the analysis of complex and interrelated factors that place adherent people at risk of viral rebound. Our aim was to build ML model to predict RNA viral rebound from medication adherence and clinical data. Patients were followed up at the Swiss interprofessional medication adherence program (IMAP). Sociodemographic and clinical variables were retrieved from the Swiss HIV Cohort Study (SHCS). Daily electronic medication adherence between 2008-2016 were analyzed retrospectively. Predictor variables included: RNA viral load (VL), CD4 count, duration of ART, and adherence. Random Forest, was used with 10 fold cross validation to predict the RNA class for each data observation. Classification accuracy metrics were calculated for each of the 10-fold cross validation holdout datasets. The values for each range from 0 to 1 (better accuracy). 383 HIV+ patients, 56% male, 52% white, median (Q1, Q3): age 43 (36, 50), duration of electronic monitoring of adherence 564 (200, 1333) days, CD4 count 406 (209, 533) cells/mm3, time since HIV diagnosis was 8.4 (4, 13.5) years, were included. Average model classification accuracy metrics (AUC and F1) for RNA VL were 0.6465 and 0.7772, respectively. In conclusion, combining adherence with other clinical predictors improve predictions of RNA.

Population Pharmacokinetics of Erlotinib in Patients With Non-small Cell Lung Cancer: Its Application for Individualized Dosing Regimens in Older Patients.

PURPOSE: Erlotinib is an oral first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for non-small cell lung cancers (NSCLC) with EGFR-activating mutations. Older patients experience more toxicities compared with younger patients at the standard recommended dose of 150 mg once daily. The aims of this study were to describe the pharmacokinetic profile of erlotinib in unselected patients with NSCLC, to quantify and explain its variability, to challenge the standard recommended dose in older patients, and to propose clinical recommendations for the therapeutic management of patients taking erlotinib. METHODS: A population pharmacokinetic model was developed using erlotinib plasma concentrations collected from patients with NSCLC participating in a routine therapeutic drug monitoring program (with the nonlinear mixed effect modeling program NONMEM). Relevant demographic characteristics, clinical factors, and co-medications were tested as potential covariates. An independent dataset was used for model validation. Simulations based on the final model allowed comparison of expected erlotinib concentrations under standard and alternative dosing regimens for smokers and for several age groups. FINDINGS: A total of 481 erlotinib plasma concentrations from 91 patients with NSCLC were used for model building and 239 plasma drug concentrations from 107 patients for model validation. A one-compartment model with first-order absorption and elimination provided the best fit. Average erlotinib CL/F with interindividual variability (%CV) was 3.8 L/h (41.5%), and V/F was 166 L (53.8%). The absorption rate constant was 1.48 h-1. The external validation showed a negligible bias of -4% (95% CI, -7 to -1) in the individual predictions, with a precision of 23%. Current smoking and use of proton pump inhibitors were associated with higher CL/F, whereas age was associated with lower CL/F. Simulations suggest that a lower dose in older patients would decrease the risk of overexposure. IMPLICATIONS: This large cohort study confirms the substantial interindividual variability in erlotinib plasma exposure and the impact of smoking and proton pump inhibitor intake. This large variability in erlotinib pharmacokinetics indicates that the standard recommended dose of 150 mg once daily is likely not appropriate to reach the expected concentrations in each patient. Concentration monitoring should be performed to individually adjust the erlotinib dosing regimen. The observed decrease in erlotinib CL/F with age suggests that a lower starting daily dose of 100 mg with concentration-guided dose adjustment would prevent overexposure and potential toxicity in older frail patients with co-morbidities.

Therapeutic Drug Monitoring of Targeted Anticancer Protein Kinase Inhibitors in Routine Clinical Use: A Critical Review.

BACKGROUND: Therapeutic response to oral targeted anticancer protein kinase inhibitors (PKIs) varies widely between patients, with insufficient efficacy of some of them and unacceptable adverse reactions of others. There are several possible causes for this heterogeneity, such as pharmacokinetic (PK) variability affecting blood concentrations, fluctuating medication adherence, and constitutional or acquired drug resistance of cancer cells. The appropriate management of oncology patients with PKI treatments thus requires concerted efforts to optimize the utilization of these drug agents, which have probably not yet revealed their full potential. METHODS: An extensive literature review was performed on MEDLINE on the PK, pharmacodynamics, and therapeutic drug monitoring (TDM) of PKIs (up to April 2019). RESULTS: This review provides the criteria for determining PKIs suitable candidates for TDM (eg, availability of analytical methods, observational PK studies, PK-pharmacodynamics relationship analysis, and randomized controlled studies). It reviews the major characteristics and limitations of PKIs, the expected benefits of TDM for cancer patients receiving them, and the prerequisites for the appropriate utilization of TDM. Finally, it discusses various important practical aspects and pitfalls of TDM for supporting better implementation in the field of cancer treatment. CONCLUSIONS: Adaptation of PKIs dosage regimens at the individual patient level, through a rational TDM approach, could prevent oncology patients from being exposed to ineffective or unnecessarily toxic drug concentrations in the era of personalized medicine.

The ABC taxonomy for medication adherence translated into French and German.

AIMS: We translated the ABC adherence taxonomy (i.e. 7 terms and their corresponding definitions) published by Vrijens et al. (2012) into French and German without changing the original meaning with the aim to promote a standardised taxonomy for medication adherence to French- and German-speaking researchers and clinicians. METHODS: A Delphi survey was performed. To generate round 1, we identified French and German synonyms for the 7 adherence terms through a literature search in PubMed. Investigators translated the original English definitions into French and German. Panellists were members of ESPACOMP-the International Society for Patient Medication Adherence; experts suggested by ESPACOMP members and first authors of medication adherence publications in French and German. Google forms were used to create online questionnaires. Delphi rounds were performed until consensus was reached. The consensus was defined according to the acceptance rate as moderate consensus (50-75%), consensus (>75-95%), and strong consensus (>95%). RESULTS: The literature search resulted in 4-6 (French) and 4-7 (German) items per English term. Delphi rounds were launched between November 2016 and April 2018. Three rounds sufficed to reach consensus on all terms and definitions from 26 French-speaking and 25 German-speaking panellists. Preferred terms for medication adherence are adhésion médicamenteuse (82%) in French and Medikamentenadhärenz (88%) in German. CONCLUSION: The use of a common terminology for medication adherence with translations in French and German will contribute to standardise the vocabulary, to harmonise research projects and ultimately ease comparison of study results among researchers and clinicians.