Search

Summary: Sickle cell disease (SCD) is an inherited red blood cell disorder associated with frequent painful events and organ damage. Hydroxyurea (HU) is the recommended evidence‐based treatment of SCD. However, among patients eligible for HU, prescription rates are low. Utilizing a scoping review approach, we summarized and synthesized relevant findings regarding provider barriers and facilitators to the prescription of HU in youth and adults with SCD and provided suggestions for future implementation strategies to improve prescription rates. Relevant databases were searched using specified search terms. Articles reporting provider barriers and/or facilitators to prescribing HU were included. A total of 10 studies met the inclusion criteria. Common barriers to the prescription of HU identified by providers included: doubts around patients' adherence to HU and their engaging in required testing, concerns about side effects, lack of knowledge, cost and patient concerns about side effects. Facilitators to the prescription of HU included beliefs in the effectiveness of HU, provider demographics and knowledge. Findings suggest significant provider biases exist, particularly in the form of negative perceptions towards patients' ability to adhere to taking HU and engaging in the required follow‐up. Improving provider knowledge and attitudes towards HU and SCD may help improve low prescription rates. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and young adults. Treatment is long and involves 2–3 years of a prolonged maintenance phase composed of oral chemotherapies. Adherence to these medications is critical to achieving good outcomes. However, adherence is difficult to determine, as there is currently no consensus on measures of adherence or criteria to determine nonadherence. Furthermore, there have been few studies in pediatric B-ALL describing factors associated with nonadherence. Thus, we performed a systematic review of literature on oral chemotherapy adherence during maintenance therapy in ALL following PRISMA guidelines. Published studies demonstrated various objective and subjective methods of assessing adherence without generalizable definitions of nonadherence. However, the results of these studies suggested that nonadherence to oral maintenance chemotherapy was associated with increased risk of relapse. Future studies of B-ALL therapy should utilize a uniform assessment of adherence and definitions of nonadherence to better determine the impact of nonadherence on B-ALL outcomes and identify predictors of nonadherence that could yield targets for adherence improving interventions. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) results in severe complications, such as anaemia and pain episodes. Hydroxyurea (HU) is efficacious in SCD, yet adherence remains low. To assess the relationship of HU adherence to health care utilization and patients' characteristics. This is a 5-year retrospective chart review. Patients' demographics and medical history were collected from the electronic medical record (EMR). HU adherence was evaluated using foetal haemoglobin "HbF%", mean corpuscular volume "MCV", and absolute neutrophil count "ANC". Age groups included children (<12 years), adolescents (12–17 years), and young adults (≥18 years). A total of 113 SCD patients on HU were included (median age 14 years, IQR 10–20; 50% female; 88% HbSS). Young adults had significantly higher HU adherence compared to adolescents and children, including higher median HbF% (24.2 vs. 12.4 vs. 8.6, p =.003), MCV (fl) (106.4 vs. 96.2 vs. 95.4, p =.01) and lower ANC (103/ml) (3.25 vs. 4.9 vs. 4.2, p =.01), respectively. Patients with chronic pain had lower HU adherence (HbF% 15.3 vs. 10.7, p =.04; ANC 3.6 vs. 6.3, p =.002; MCV 102.3 vs. 93.1, p =.1). Patients with higher HbF or MCV and lower ANC had significantly less frequent emergency room visits (rs=–0.26, p =.01; rs=–0.23, p =.01; rs=0.24, p =.01) and hospitalizations (rs=–0.27, p =.01; rs=–0.31, p =.01; rs=0.21, p =.02) as well as shorter length of stays (rs=–0.27, p =.0045; rs=–.34, p = 0.004; rs=0.23, p =.02), respectively. Similar trends in HU adherence and health care utilization were seen in subgroup analysis of only HbSS patients. There was no significant association of HU adherence to patients' sex, socio-economic status, distance from hospital, and HU duration. Young adults with SCD had significantly higher HU adherence compared to children and adolescents. Patients with lower HU adherence and/or chronic pain had increased health care utilization. Future studies examining barriers to adherence and evaluating interventions to optimize HU adherence in SCD are warranted. Young adults with SCD had significantly higher HU adherence, as reflected in their laboratory markers, compared to children and adolescents. Patients with higher HU adherence and/or those without chronic pain had lower or less frequent health care utilization. No significant association of HU adherence to patients' sex, socio-economic status and distance from hospital. [ABSTRACT FROM AUTHOR]

Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents. This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria. Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report (n = 15/36, 41.7%), and pill count (n = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills (n = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in "categories" with different levels of adherence (n = 29) or "quantitatively" as a percentage of medication taken out of those prescribed (n = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis. Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients. Predictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort. Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes. Inadequate adherence to ICT is associated with increased lifetime health costs. There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients. [ABSTRACT FROM AUTHOR]

Background: Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. Objective: We aimed to describe the impact of the COVID-19 pandemic on the implementation of an mHealth behavioral intervention for improving hydroxyurea adherence among patients with SCD. Methods: The first 2 sites initiated enrollment 3 months prior to the start of the pandemic (November 2019 to March 2020). During implementation, site A clinics shut down for 2 months and site B clinics shut down for 9 months. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to evaluate the implementation and effectiveness of the intervention. mHealth implementation was assessed based on patients' daily app use. Adherence to hydroxyurea was calculated as the proportion of days covered (PDC) from prescription records over the first 12 and 24 weeks after implementation. A linear model examined the relationship between app usage and PDC change, adjusting for baseline PDC, lockdown duration, and site. We conducted semistructured interviews with patients, health care providers, administrators, and research staff to identify factors associated with mHealth implementation and effectiveness. We used a mixed methods approach to investigate the convergence of qualitative and quantitative findings. Results: The percentage of patients accessing the app decreased after March 15, 2020 from 86% (n=55) to 70% (n=45). The overall mean PDC increase from baseline to week 12 was 4.5% (P=.32) and to week 24 was 1.5% (P=.70). The mean PDC change was greater at site A (12 weeks: 20.9%; P=.003; 24 weeks: 16.7%; P=.01) than site B (12 weeks: -8.2%; P=.14; 24 weeks: -10.3%; P=.02). After adjustment, PDC change was 13.8% greater in those with increased app use after March 15, 2020. Interview findings indicated that site B's closure during COVID-19 had a greater impact, but almost all patients reported that the InCharge Health app helped support more consistent medication use. Conclusions: We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may "insulate" the implementation of interventions to increase medication adherence. [ABSTRACT FROM AUTHOR]

Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassemia. However, the role that adherence to ICT plays in health-related outcomes is less well known. Our objectives were to identify adherence rates of ICT, and to assess methods of measurement, predictors of adherence, and adherence-related health outcomes in the literature published between 1980 and 2020. Of 543 articles, 43 met the inclusion criteria. Studies measured ICT adherence, predictors, and/or outcomes associated with adherence. Most studies were across multiple countries in Europe and North America (n = 8/43, 18.6%), recruited in clinics (n = 39/43, 90.7%), and focused on β-thalassemia (β-thal) (n = 25/43, 58.1%). Common methods of assessing ICT adherence included patient self-report (n = 24/43, 55.8%), pill count (n = 9/43, 20.9%), prescription refill history (n = 3/43, 7.0%), provider scoring (n = 3/43, 7.0%), and combinations of methods (n = 4/43, 9.3%). Studies reported adherence either in 'categories' with different levels of adherence (n = 24) or 'quantitatively' as a percentage of doses of medication taken out of those prescribed (n = 17). Adherence levels varied (median 91.7%, range 42.0–99.97%). Studies varied in sample size and methods of adherence assessment and reporting, which prohibited meta-analysis. Due to a lack of consensus on how adherence is defined, it is difficult to compare ICT adherence reporting. Further research is needed to establish guidelines for assessing adherence and identifying suboptimal adherence. Behavioral digital interventions have the potential to optimize ICT adherence and health outcomes. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) complications lead to poor health-related quality of life (HRQOL) and increased healthcare utilization in this population, which could be mitigated with hydroxyurea therapy; however, adherence is suboptimal. We assessed the relationship of healthcare utilization to hydroxyurea adherence and HRQOL amongst youth with SCD. Methods: Thirty-four patients with SCD (median age 14 years, IQR 12-18) on hydroxyurea participated in this cross-sectional study and completed Morisky Adherence Scale 8-items and Patient Reported Outcomes Measurement Information System (PROMIS®) HRQOL measures. A medical chart review was conducted to assess healthcare utilization. Results: Participants with more frequent hospitalizations and emergency room (ER) visits and longer length of stay (LOS) had significantly lower fetal hemoglobin (rs=-0.44; rs=-0.45; rs=-0.46, p < 0.05) and mean corpuscular volume (rs=-0.47; rs=-0.42; rs=-0.48, p < 0.05), respectively. More frequent hospitalizations and ER visits and longer LOS correlated significantly with worse fatigue (rs=0.51; rs=0.41; rs=0.53, p < 0.05), pain (rs=0.41; rs=0.38; rs=0.47, p < 0.05), physical function mobility (rs=-0.67; rs=-0.59; rs=-0.67, p < 0.05), depression (rs=0.38; rs=0.31; rs=0.42, p < 0.05), and social isolation (rs=0.76; rs=0.76; rs=-0.84, p < 0.05), respectively. Conclusions: We conclude that increased healthcare utilization in youth with SCD is associated with low adherence to hydroxyurea and worse HRQOL domain scores. It is important emphasize the clinical benefits of high adherence to hydroxyurea, particularly among youth with SCD. Future longitudinal studies are warranted to assess the directionality of these relationships, and may reveal modifiable behavioral factors associated with early changes in hydroxyurea adherence levels. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) patients have impaired domains of health-related quality of life (HRQOL). Hydroxyurea is safe and efficacious in SCD; however, adherence is suboptimal, and patients' perceptions are poorly understood amongst adolescents and young adults (AYA). Study objectives were to: (1) examine patients' perceptions of SCD and hydroxyurea; and (2) explore the relationship of their perceptions to clinical characteristics, HRQOL domains and hydroxyurea adherence.Methods: Thirty-four SCD patients on hydroxyurea (≥6 months) participated in a single-institution study. Study measures included Brief-Illness Perceptions Questionnaire, ©Modified Morisky Adherence Scale 8-items, and Patient Reported Outcomes Measurement Information System (PROMIS®). We assessed the relationship of patients' perceptions to hydroxyurea adherence using Wilcoxon rank-sum test, the number of hospitalizations using Kruskal-Wallis test, and the number of ED visits, adherence level, HRQOL domain scores using Spearman's rho correlations. We conducted a sub-analysis in HbSS patients to evaluate the relationship of patients' perceptions to laboratory markers of hydroxyurea adherence.Results: Participants were 59% male and 91% Black, and had a median age of 13.5 (range 12-18) years. Participants with ≥4 hospitalizations over 1-year prior (using electronic medical chart review) reported more negative perceptions of SCD-related symptoms and emotional response, and perceived hydroxyurea as less beneficial; all p-values ≤0.01. Most participants (74%) reported low hydroxyurea adherence. Participants with higher hydroxyurea adherence perceived more hydroxyurea benefits (r s = 0.44, p < 0.01) and had better emotional response to SCD (r s = -0.44, p = 0.01). In a sub-analysis of HbSS patients, perceived benefits of hydroxyurea positively correlated with HbF (r s = 0.37, p = 0.05) and MCV values (r s = 0.35, p = 0.05). Participants with more negative perceptions of SCD-related consequences, concerns, and emotional response, and fewer perceived hydroxyurea benefits reported worse fatigue (r s = 0.68; r s = 0.44; r s = 0.74; r s = -0.60), pain (r s = 0.56; r s = 0.54; r s = 0.63; r s = -0.39), anxiety (r s = 0.55; r s = 0.58; r s = 0.56; r s = -0.47), and depression (r s = 0.64; r s = 0.49; r s = 0.70; r s = -0.62), respectively, all p-values <0.05.Conclusions: Dynamics influencing hydroxyurea adherence are multifactorial, and understanding patients' perceptions is critical to overcoming adherence barriers. Patients' favorable perceptions correlated with greater adherence and better HRQOL domain scores. Prospective evaluation of patients' perceptions of SCD and hydroxyurea in relation adherence, HRQOL domains and clinical outcomes is warranted. [ABSTRACT FROM AUTHOR]

Objectives To identify barriers to hydroxyurea adherence (negative beliefs, access, and/or recall barriers), and their relationship to adherence rates and health-related quality of life ( HRQOL) among adolescents and young adults ( AYA) with sickle cell disease ( SCD). Methods A cross-sectional survey was administered to 34 AYAs (12-22 years old) in SCD clinics from January to December 2015. Study measures included Brief Medication Questionnaire, Modified Morisky Adherence Scale 8-items, visual analog scale, and Patient Reported Outcomes Measurement Information System. Results Participants (59% male; 91% Black) had a median age of 13.5 years ( IQR 12-18). Participants reported negative beliefs (32%), recall barriers (44%), and access barriers (32%). Participants with recall barriers reported worse pain ( P=.02), fatigue ( P=.05), and depression ( P=.05). The number of adherence barriers inversely correlated with adherence level using © MMAS-8 ( rs=−.38, P=.02) and VASdose ( rs=−.25, P=.14) as well as MCV ( rs=−.45, P=.01) and HbF% ( rs=−.36, P=.05), suggesting higher hydroxyurea adherence in patients with fewer barriers. Conclusions Patients with fewer barriers to hydroxyurea adherence were more likely to have higher adherence rates and better HRQOL scores. Routine assessment of hydroxyurea adherence and its related barriers could provide actionable information to improve adherence rates, HRQOL, and other clinical outcomes. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. 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 in heart transplant patients varies considerably. • Socio-demographics, mental health, and poor support correlate with nonadherence. • Nonadherence may lead to coronary artery disease and acute late rejection. • Simplified dosing regimen and a mobile app intervention were associated with improved adherence. [ABSTRACT FROM AUTHOR]

The number of children and adolescents with chronic health conditions (CHCs) has doubled over the past two decades. Medication adherence is a key component of disease management within these groups. Low adherence to prescribed medications is a known problem in adolescents with CHCs and is related to health outcomes, including quality of life, disease complications, and mortality. Adolescence is a critical time to create routines and health behaviors that optimize disease self-management and transition to adult care. The mounting interest in the development and use of mobile health tools provides novel opportunities to connect patients, particularly adolescents, with their providers outside of the clinic and to improve health outcomes. There is growing evidence to support the efficacy of technology-based approaches, in particular text-messaging and mobile apps, to improve adherence behavior in adolescents, although cost-effectiveness and long-term health benefits remain unclear. In this short viewpoint article, we review some important considerations for promoting medication adherence in adolescents with CHCs using technology-based approaches. [ABSTRACT FROM AUTHOR]