A Systematic Review of Adherence to Immunosuppression among Pediatric Heart Transplant Patients.

After pediatric heart transplant, commitment to lifelong immunosuppression is crucial to maintaining graft health. However, a review of the current literature surrounding adherence to immunosuppression in pediatric heart transplant patients is lacking. This systematic review aims to summarize the current landscape of adherence to immunosuppression in pediatric heart transplant patients. We conducted searches in PubMed MEDLINE, Embase, CENTRAL register of Controlled Trials (Wiley), and Scopus, from inception to March 2020. Studies were eligible if they outlined an aspect of adherence to immunosuppression and the measurement of adherence was performed with an objective or otherwise validated measure of adherence (e.g., drug levels, adherence questionnaires). The titles/abstracts of 880 articles were reviewed. After initial screening, 106 articles underwent full text review. As such, 14 articles were included in the final review. Baseline adherence estimates varied greatly, with most values between 40% and 70%. Nonadherence to immunosuppression is associated with worse outcomes (rejection, hospitalization, mortality), impaired quality of life, and mental health concerns in pediatric heart transplant patients. As nonadherence to immunosuppression is common and associated with worse outcomes, there is a need for further development and evaluation of interventions in this space.

Cardiovascular Imaging for Systemic Sclerosis Monitoring and Management.

Systemic sclerosis (SSc) is a complex connective tissue disease with multiple clinical and subclinical cardiac manifestations. SSc can affect most structural components of the heart, including the pericardium, myocardium, valves, and conduction system through a damaging cycle of inflammation, ischemia, and fibrosis. While cardiac involvement is the second leading SSc-related cause of death, it is frequently clinically silent in early disease and often missed with routine screening. To facilitate identification of cardiac disease in this susceptible population, we present here a review of cardiac imaging modalities and potential uses in the SSc patient population. We describe well-characterized techniques including electrocardiography and 2D echocardiography with Doppler, but also discuss more advanced imaging approaches, such as speckle-tracking echocardiography, cardiovascular magnetic resonance imaging (CMR), and stress imaging, among others. We also suggest an algorithm for the appropriate application of these modalities in the workup and management of patients with SSc. Finally, we discuss future opportunities for cardiac imaging in SSc research to achieve early detection and to optimize treatment.

Adherence to immunosuppression in adult heart transplant recipients: A systematic review.

BACKGROUND: Successful maintenance of a heart transplant (HTx) graft requires adherence to a triple-drug regimen of immunosuppression. However, achieving adequate adherence can be difficult secondary to complicated dosing regimens, side effects, and mental/emotional barriers. A detailed review of current patterns of adherence to immunosuppression in adult HTx recipients is lacking. OBJECTIVE: This systematic review aims to detail the current landscape of adherence to immunosuppression in adult heart transplant patients, including the measurement of adherence, correlates to adherence, health outcomes associated with nonadherence, as well as strategies to improve adherence in HTx patients. METHODS: We conducted searches in PubMed MEDLINE, Embase, CENTRAL register of Controlled Trials (Wiley), and Scopus, from inception to March 2020. Studies were eligible if they outlined an aspect of adherence (as noted above in the objective) to immunosuppression in adult HTx patients. The HTx cohort had to contain at least 10 patients and measurement of adherence had to be done with an objective or otherwise validated measure of adherence (e.g. drug levels, automated pill bottles or adherence questionnaires). Two authors independently screened the articles for inclusion, then subsequently reviewed the full texts of the included articles. Data was extracted into standardized forms and bias evaluations were done using the Newcastle-Ottawa or modified Newcastle-Ottawa tools, depending on the study type. The authors followed all guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: The titles/abstracts of 880 articles were reviewed. Ultimately, 23 articles were included in the final review. The median number of participants was 101, with a range of 19 to 1397. Studies provided information on baseline levels of adherence (17 studies), correlates to adherence (14 studies), health outcomes related to nonadherence (3 studies) and interventions to improve adherence (3 studies). Baseline adherence estimates varied greatly depending on the adherence measure. Multiple significant correlates to nonadherence exist and appear to affect patients with certain sociodemographic backgrounds, those with psychological/psychiatric comorbidities and those with poor support structures. Nonadherence is associated with transplant coronary artery disease and acute late rejection; it may also be associated with long-term mortality. Finally, a simplified dosing regimen with once-a-day tacrolimus as well as use of a mobile phone-based intervention were associated with improved adherence. Bias scores were most deficient due to self-reported outcomes in 18 studies, and lack of controls/adjustments for confounders, in 7 studies. CONCLUSIONS: Adherence to immunosuppression in transplant patients varies, but is associated with observable and modifiable factors which are worth addressing. Further high-quality studies regarding strategies to improve adherence are needed in the literature.

Adherence to Immunosuppression Medications among Heart Transplant Recipients: Challenges, Opportunities, and Potential Role of Digital Approaches in the COVID-19 Era.

Society and medical practice have been restructured dramatically to avoid further spread of the COVID-19 virus; telehealth/telemedicine, mask wearing, and nationwide social distancing practices have become widespread. However, we still face unprecedented challenges in fields where patients require frequent and active follow-up visits for monitoring, including that of solid-organ transplant, and in particular, heart transplant. Adherence to immunosuppression remains a unique challenge in heart transplantation, especially during the COVID-19 pandemic. Failure to adhere to immunosuppression can have disastrous consequences, including graft rejection and death. In this article, we discuss challenges related to adherence to immunosuppression medications among heart transplant recipients, as well as opportunities to leverage digital approaches and interventions to monitor and optimize adherence behavior and health outcomes in this population.

When evidence is lacking: a mixed-methods approach for the development of practice guidance in liver transplantation.

BACKGROUND: Most interventions for conditions with a small cohort size, such as transplantation, are unlikely to be part of a clinical trial. When condition-specific evidence is lacking, expert consensus can offer more precise guidance to improve care. Management of cardiovascular risk in liver-transplant recipients is one example for which clinicians have, to date, adapted evidence-based guidelines from studies in the general population. However, even when consensus is achieved, implementation of practice guidance is often inadequate and protracted. We report on a novel mixed-methods approach, the Northwestern Method©, for the development of clinical-practice guidance when condition-specific evidence is lacking. We illustrate the method through the development of practice guidance for managing cardiovascular risk in liver-transplant recipients. METHODS: The Northwestern Method© consists of (i) adaptation of relevant, existing, evidence-based clinical-practice guidelines for the target population; (ii) consensus by experts of the proposed practice guidance; (iii) identification of barriers to guidance adherence in current practice; and (iv) recommendation for implementation and dissemination of the practice guidance. The method is based on an iterative, user-centered approach in which the needs, wants, and limitations of all end users, including patients, are attended to at each stage of the design and development process. CONCLUSIONS: The Northwestern Method© for clinical-practice-guidance development uses a mixed-methods approach to bring together broad representation from multiple disciplines and practice settings to develop consensus considering the unique needs and preferences of patients, caregivers, and practitioners who are directly impacted by clinical-practice-guidance recommendations. We hypothesize that a priori involvement of end users in the guidance-development process will lead to sustainable implementation of guidance statements into clinical practice.

Access to Technology and Preferences for an mHealth Intervention to Promote Medication Adherence in Pediatric Acute Lymphoblastic Leukemia: Approach Leveraging Behavior Change Techniques.

BACKGROUND: Suboptimal adherence to 6-mercaptopurine (6-MP) is prevalent in pediatric acute lymphoblastic leukemia (ALL) and associated with increased risk of relapse. Rapid uptake of personal technology makes mobile health (mHealth) an attractive platform to promote adherence. OBJECTIVE: Study objectives were to examine access to mobile technology and preferences for an mHealth intervention to improve medication adherence in pediatric ALL. METHODS: A cross-sectional survey was administered in oncology clinic to parents of children with ALL as well as adolescents and young adults (AYAs) with ALL receiving maintenance chemotherapy. RESULTS: A total of 49 parents (median age [IQR] 39 [33-42] years; female 76% [37/49]) and 15 patients (median age [IQR] 17 [16-19]; male 80% [12/15]) participated. All parents and AYAs owned electronic tablets, smartphones, or both. Parents' most endorsed mHealth app features included a list of medications (71%, 35/49), information about 6-MP (71%, 35/49), refill reminders (71%, 35/49), and reminders to take 6-MP (71%, 35/49). AYAs' most endorsed features included refill reminders (73%, 11/15), reminders to take 6-MP (73%, 11/15), and tracking 6-MP (73%, 11/15). CONCLUSIONS: Parents and AYAs reported ubiquitous access to mobile technology and strong interest in multiple adherence-specific mHealth app features. Parents and AYAs provided valuable insight into preferred features for a multifunctional behavioral intervention (mHealth app) to promote medication adherence in pediatric ALL.

Mobile Phone-Based Behavioral Interventions in Pregnancy to Promote Maternal and Fetal Health in High-Income Countries: Systematic Review.

BACKGROUND: Chronic diseases have recently had an increasing effect on maternal-fetal health, especially in high-income countries. However, there remains a lack of discussion regarding health management with technological approaches, including mobile health (mHealth) interventions. OBJECTIVE: This study aimed to systematically evaluate mHealth interventions used in pregnancy in high-income countries and their effects on maternal health behaviors and maternal-fetal health outcomes. METHODS: This systematic review identified studies published between January 1, 2000, and November 30, 2018, in MEDLINE via PubMed, Cochrane Library, EMBASE, CINAHL, PsycINFO, Web of Science, and gray literature. Studies were eligible for inclusion if they included only pregnant women in high-income countries and evaluated stand-alone mobile phone interventions intended to promote healthy maternal beliefs, behaviors, and/or maternal-fetal health outcomes. Two researchers independently reviewed and categorized aspects of full-text articles, including source, study design, intervention and control, duration, participant age, attrition rate, main outcomes, and risk of bias. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the study was registered in PROSPERO before initiation. RESULTS: Of the 2225 records examined, 28 studies were included and categorized into 4 themes: (1) gestational weight gain, obesity and physical activity (n=9); (2) smoking cessation (n=9); (3) influenza vaccination (n=2); and (4) general prenatal health, preventive strategies, and miscellaneous topics (n=8). Reported sample sizes ranged from 16 to 5243 with a median of 91. Most studies were performed in the United States (18/28, 64%) and were randomized controlled trials (21/28, 75%). All participants in the included studies were pregnant at the time of study initiation. Overall, 14% (4/28) of studies showed association between intervention use and improved health outcomes; all 4 studies focused on healthy gestational weight. Among those, 3 studies showed intervention use was associated with less overall gestational weight gain. These 3 studies involved interventions with text messaging or an app in combination with another communication strategy (Facebook or email). Regarding smoking cessation, influenza vaccination, and miscellaneous topics, there was some evidence of positive effects on health behaviors and beliefs, but very limited correlation with improved health outcomes. Data and interventions were heterogeneous, precluding a meta-analysis. CONCLUSIONS: In high-income countries, utilization of mobile phone-based health behavior interventions in pregnancy demonstrates some correlation with positive beliefs, behaviors, and health outcomes. More effective interventions are multimodal in terms of features and tend to focus on healthy gestational weight gain.

Applying the COM-B model to patient-reported barriers to medication adherence in pediatric acute lymphoblastic leukemia.

BACKGROUND: Adherence to oral chemotherapy, including 6-mercaptopurine (6-MP), is suboptimal in pediatric acute lymphoblastic leukemia (ALL), which is associated with increased risk of relapse. Study objectives were to examine self-reported adherence to 6-MP and related barriers to adherence, mapped to the capability, opportunity, motivation, and behavior (COM-B) model for behavior change. PROCEDURE: Forty-nine parents (median, 39 years old; 76% females) and 15 patients (median, 17 years old, 20% females) completed the study survey. RESULTS: Suboptimal adherence was reported in 43% of parents and 73% of patients. Most parents and patients (80% and 90%, respectively) reported ≥1 adherence barrier. Parents reported difficulty helping their child meet others with ALL (43%), contacting community organizations (39%), and meeting other parents (37%). Patients reported difficulty finding out what their medications are (40%), finding out what 6-MP does (47%), and meeting other patients (40%). Using the COM-B, we found that parents and patients endorsed barriers in multiple components, especially physical (55%, 67%) and social opportunity (56%, 47%), highlighting that barriers to adherence may be multifaceted. CONCLUSIONS: Our results suggest that parents and patients with ALL face various prevalent barriers to medication adherence and provide insight into the development of behavioral interventions focused on promoting adherence, which is essential to prevent relapse and optimize health outcomes in ALL.