Non-adherence after heart transplantation (HTx) is a significant problem. The main objective of this study was to evaluate if a mHealth strategy is more effective than standard care in improving adherence and patients’ experience in heart transplant recipients. Methods: This was a single-center, randomized controlled trial (RCT) in adult recipients >1.5 years post-HTx. Participants were randomized to standard care (control group) or to the mHeart Strategy (intervention group). For patients randomized to the mHeart strategy, multifaceted theory-based interventions were provided during the study period to optimize therapy management using the mHeart mobile application. Patient experience regarding their medication regimens were evaluated in a face-to-face interview. Medication adherence was assessed by performing self-reported questionnaires. A composite adherence score that included the SMAQ questionnaire, the coefficient of variation of drug levels and missing visits was also reported. Results: A total of 134 HTx recipients were randomized (intervention N = 71; control N = 63). Mean follow-up was 1.6 (SD 0.6) years. Improvement in adherence from baseline was significantly higher in the intervention group versus the control group according to the SMAQ questionnaire (85% vs. 46%, OR = 6.7 (2.9; 15.8), p-value < 0.001) and the composite score (51% vs. 23%, OR = 0.3 (0.1; 0.6), p-value = 0.001). Patients’ experiences with their drug therapy including knowledge of their medication timing intakes (p-value = 0.019) and the drug indications or uses that they remembered (p-value = 0.003) significantly improved in the intervention versus the control group. Conclusions: In our study, the mHealth-based strategy significantly improved adherence and patient beliefs regarding their medication regimens among the HTx population. The mHeart mobile application was used as a feasible tool for providing long-term, tailor-made interventions to HTx recipients to improve the goals assessed.

Background and Purpose: Around 40– 50% of diffuse large-B cell lymphoma (DLBCL) patients suffer from refractory disease or relapse after R-CHOP first-line treatment. Many ongoing clinical trials for DLBCL patients involve microtubule targeting agents (MTAs), however, their anticancer activity is limited by severe side effects. Therefore, we chose to improve the therapeutic window of the MTA monomethyl auristatin E developing a nanoconjugate, T22-AUR, that selectively targets the CXCR4 receptor, which is overexpressed in many DLBCL cells (CXCR4⁺) and associated with poor prognosis. Methods: The T22-AUR specificity towards CXCR4 receptor was performed by flow cytometry in different DLBCL cell lines and running biodistribution assays in a subcutaneous mouse model bearing CXCR4⁺ DLBCL cells. Moreover, we determined T22-AUR cytotoxicity using cell viability assays, cell cycle analysis, DAPI staining and immunohistochemistry. Finally, the T22-AUR antineoplastic effect was evaluated in vivo in an extranodal CXCR4⁺ DLBCL mouse model whereas the toxicity analysis was assessed by histopathology in non-infiltrated mouse organs and by in vitro cytotoxic assays in human PBMCs. Results: We demonstrate that the T22-AUR nanoconjugate displays CXCR4-dependent targeting and internalization in CXCR4⁺ DLBCL cells in vitro as well as in a subcutaneous DLBCL mouse model. Moreover, it shows high cytotoxic effect in CXCR4⁺ DLBCL cells, including induction of G2/M mitotic arrest, DNA damage, mitotic catastrophe and apoptosis. Furthermore, the nanoconjugate shows a potent reduction in lymphoma mouse dissemination without histopathological alterations in non-DLBCL infiltrated organs. Importantly, T22-AUR also exhibits lack of toxicity in human PBMCs. Conclusion: T22-AUR exerts in vitro and in vivo anticancer effect on CXCR4⁺ DLBCL cells without off-target toxicity. Thus, T22-AUR promises to become an effective therapy for CXCR4⁺ DLBCL patients.

Background: Medication nonadherence in heart transplant recipients (HTxR) is related to graft loss and death. mHeart is a mobile app that uses electronic patient-reported outcome measures (ePROMs) to identify and manage medication nonadherence in the outpatient heart transplant (HTx) population. Objective: The study primarily aimed to validate mHeart to measure medication nonadherence in early stage HTxR by assessing the psychometric properties of ePROMs. The secondary aims were to (1) measure patient satisfaction with the mHeart tool and its usability and (2) explore the impact of a theory-based treatment on medication nonadherence rates to determine its scalability to larger research. Methods: A prospective study was conducted in the outpatient clinic of a tertiary hospital. All consecutive early stage HTxR (<1.5 years from HTx) were included. The ePROM psychometric properties assessed were validity, reliability, responsiveness, interpretability, and burden. ePROMs comprised the 4-item Morisky-Green-Levine questionnaire and an adapted version of the Haynes-Sackett questionnaire. The Simplified Medication Adherence Questionnaire (SMAQ) was also applied on-site. Three consecutive medication nonadherence assessments were performed by a transplant pharmacist. To improve medication nonadherence, theory-based interventions were delivered in a 1-month period. Patient satisfaction was assessed by a semiquantitative Web-based survey at the end of the study. Results: We included 31 early stage HTxR (age: mean 54 years, SD 12 years), and 71% (22/31) of them were men. The HTxR were taking a mean 13 (SD 4; range 7-18) drugs per day. A total of 42% (13/31) of patients were unaware of the consequences of medication nonadherence, and 39% (12/31) of patients were nonadherent to immunosuppressive treatment. The content validity measure showed excellent levels of expert panel agreement for the Haynes-Sacket (14/14, 100%) and Morisky-Green-Levine (13/14, 93%) questionnaires. SMAQ and Morisky-Green-Levine ePROMs showed similar measurement domains (convergent validity, phi=0.6, P<.001), which, as expected, differed from Haynes-Sackett ePROMs (divergent validity, phi=0.3, P=.12). Reliability assessment revealed a very strong association between ePROM and on-site PROMs (phi>0.7, P<.001). Reproducibility was moderate (Haynes-Sackett κ=0.6, P<.002) or poor (Morisky-Green-Levine κ=0.3, P=.11) because of unexpected improved medication adherence rates during the test-retest period. According to responsiveness, the theory-based multifaceted intervention program improved medication nonadherence by 16% to 26% (P<.05). A burden analysis showed that ePROMs could potentially overcome traditional on-site limitations (eg, automatic recording of ePROM responses in the hospital information system). The mean score for overall patient satisfaction with the mHeart approach was 9 (SD 2; score range: 0-10). All 100% (29/29) of patients surveyed reported that they would recommend the mHeart platform to other HTxR. Conclusions: ePROMs adhered to the quality standards and successfully identified medication nonadherence in the HTx population, supporting their widespread use. The theory-based intervention program showed a promising improvement in medication adherence rates and produced excellent patient satisfaction and usability scores in HTxR.

BACKGROUND Adherence problems, interactions and higher rate of risk activities have been observed in HIV individuals using recreational drugs. Our aim was to describe recreational drug use in both HIV individuals and general population in Europe, and to assess at what extent HIV guidelines address this issue. METHODS Data on recreational drug use across Europe were obtained from the European Monitoring Centre for Drugs and Drug Addiction for the general population, and through Pubmed search. for HIV patients. We assessed the incorporation of recreational drug issues in HIV treatment guidelines for the following topics: a) recreational drugs; b) adherence to antiretrovirals; c) interactions; d) transmission risk. Guidelines included: World Health Organization; European Aids Clinical Society; U.S. Department of Health and Human Services; International Antiviral Society-USA; and seven European national guidelines. RESULTS 29 countries reported recreational drug use in general population. The highest prevalences were observed for Cannabis (i.e. 8-10% in Spain, France and Czech Republic) followed by cocaine, amphetamines and ecstasy. The 13 studies selected in the systematic review showed a great variability in recreational drug use on the HIV population. Apart from classical recreational drugs, we found a relevant use of new drugs including sexual experience enhancers. Polydrug consumption was about 50% in some studies. Most guidelines included general information about recreational drugs, showing great variability on the inclusion of the evaluated topics. We found more specific, evidence-based recommendations on interactions, followed by medication adherence and transmission risk. CONCLUSIONS Available data on the people living with HIV suggest a higher use of recreational drugs than in the general population, which is already relevant. However, recreational drug issues should be included or addressed more thoroughly in most guidelines.

Background: Rare diseases (RDs) are a heterogeneous group of complex and low-prevalence conditions in which the time to establish a definitive diagnosis is often too long. In addition, for most RDs, few to no treatments are available and it is often difficult to find a specialized care team. Objectives: The project “acERca las enfermedades raras” (in English: “bringing RDs closer”) is an initiative primary designed to generate a consensus by a multidisciplinary group of experts to detect the strengths and weaknesses in the public healthcare system concerning the comprehensive care of persons living with a RD (PLWRD) in the region of Catalonia, Spain, where a Network of Clinical Expert Units (Xarxa d’Unitats de Expertesa Clínica or XUEC) was created and is being implemented since 2015. The additional primary aim was to propose recommendations to solve or improve the limitations found. Methods: A task force of 13 participants with multidisciplinary expertise on RDs completed a questionnaire and participated in two focus groups. A document was drafted with an item series of strengths and weaknesses of the healthcare system regarding the care of PLWRD, and a set of proposals or recommendations to overcome the problems identified. Results: The Catalan Government healthcare model of XUECs for the comprehensive care for RDs is currently valid and adapted to the needs of PLWRD and their families since its strategic optimal and operational framework, and it is aligned with the European Reference Networks (ERNs) thematic areas. The problems found in the current healthcare model were grouped into ten main areas: (1) the healthcare model for RDs; (2) coordination with primary healthcare providers and other tertiary and secondary hospitals; (3) access to and coordination with non-medical services; (4) the role of case manager in the XUEC; (5) genetic diagnosis; (6) undiagnosed patients; (7) treatments; (8) referring process, continuous follow-up, and transition from pediatric to adult centers; (9) research and education for professionals; and (10) associations of PLWRD and their families (patients’ advocacy). The need for more resources was currently detected as the common factor for most of them. Ten key recommendations to improve the healthcare system regarding RDs were postulated. Conclusions: Catalonia has established a unique healthcare model for RDs in Spain, with clear strengths and advantages. However, after analyzing them, the experts suggested that new governmental political and administrative decisions are needed to ensure the efficient implementation of a healthcare plan for PLWRD in Catalonia, which could be applied to other regions and nations worldwide.

Background: Solid organ transplantation could be the only life-saving treatment for end-stage heart failure. Nevertheless, multimorbidity and polypharmacy remain major problems after heart transplant. A technology-based behavioral intervention model was established to improve clinical practice in a heart transplant outpatient setting. To support the new strategy, the mHeart app, a mobile health (mHealth) tool, was developed for use by patients and providers. Objective: The primary objective of this study was to describe the implementation of the mHeart model and to outline the main facilitators identified when conceiving an mHealth approach. The secondary objectives were to evaluate the barriers, benefits, and willingness to use mHealth services reported by heart transplant recipients and cardiology providers. Methods: This was an implementation strategy study directed by a multidisciplinary cardiology team conducted in four stages: design of the model and the software, development of the mHeart tool, interoperability among systems, and quality and security requirements. A mixed methods study design was applied combining a literature review, several surveys, interviews, and focus groups. The approach involved merging engineering and behavioral theory science. Participants were chronic-stage heart transplant recipients, patient associations, health providers, stakeholders, and diverse experts from the legal, data protection, and interoperability fields. Results: An interdisciplinary and patient-centered process was applied to obtain a comprehensive care model. The heart transplant recipients (N=135) included in the study confirmed they had access to smartphones (132/135, 97.7%) and were willing to use the mHeart system (132/135, 97.7%). Based on stakeholder agreement (>75%, N=26), the major priorities identified of the mHealth approach were to improve therapy management, patient empowerment, and patient-provider interactions. Stakeholder agreement on the barriers to implementing the system was weak (<75%). Establishing the new model posed several challenges to the multidisciplinary team in charge. The main factors that needed to be overcome were ensuring data confidentiality, reducing workload, minimizing the digital divide, and increasing interoperability. Experts from various fields, scientific societies, and patient associations were essential to meet the quality requirements and the model scalability. Conclusions: The mHeart model will be applicable in distinct clinical and research contexts, and may inspire other cardiology health providers to create innovative ways to deal with therapeutic complexity and multimorbidity through health care systems. Professionals and patients are willing to use such innovative mHealth programs. The facilitators and key strategies described were needed for success in the implementation of the new holistic theory–based mHealth strategy.