Specifying sickle cell disease interventions: A study protocol of the Sickle Cell Disease Implementation Consortium (SCDIC)

Abstract Background Sickle cell disease (SCD) is an inherited blood disorder that results in a lifetime of anemia, severe pain, and end-organ damage that can lead to premature mortality. While the SCD field has made major medical advances, much needs to be done to improve the quality of care for people with SCD. This study capitalizes on the Sickle Cell Disease Implementation Consortium (SCDIC), a consortium of eight academic sites aiming to test implementation strategies that could lead to more accelerated application of the NHLBI guidelines for treating SCD. This report documents the process to support the consortium by specifying the interventions being developed. Methods This study consists of three steps. The Principal Investigator of each site and two site representatives who are knowledgeable of the intervention (e.g., study coordinator or the person delivering the intervention) will answer an online survey aiming to capture components of the interventions. This survey will be completed by the site representatives three times during the study: during the development of the interventions, after one year of the interventions being implemented, and at the end of this study (after 2 years). A site visit and semi-structured interview (Step 2) in the first year of the process will capture the context of the sites. Step 3 comprises of the development of a framework with the details of the multi-component SCDIC interventions at the sites. Discussion The outcome of this study, a framework of the SCDIC, will enable accurate replication and extension of published research, facilitating the translation of SCD studies to diverse populations and settings and allowing for theory testing of the effects of the intervention components across studies in different contexts and for different populations. Trial registration ClinicalTrial.Gov (#NCT03380351). Registered December 21, 2017

Development and feasibility of a home-based education model for families of children with sickle cell disease

BACKGROUND: Children with sickle cell disease (SCD) commonly have cognitive deficits, even among toddlers. Much medical literature emphasizes disease-based factors to account for these deficits. However, the social environment plays a large role in child development. To address the specific needs of early childhood, a monthly hospital-based education program was initiated to educate parents about child development. Education sessions were poorly attended (20-25%) and deemed unsuccessful. This study describes the development and implementation of a home-based education service to teach parents about SCD, developmental milestones and positive parenting techniques. METHODS: This was a prospective, single-arm intervention to study the feasibility of a home-based caregiver education program for families with infants and toddlers with SCD. Parents of children aged 0-3 years with SCD from one Midwestern hospital were approached to participate in a home-based program. The program followed the Born to Learn™ curriculum provided through the Parents as Teachers™ National Center. Reminder calls or texts were provided the day before each visit. Results of the first twenty-six months of the program are presented. RESULTS: A total of 62% (56 of 91) of families approached agreed to participate; all were African American. The majority of caregivers were single mothers with a high school education or less and whose children had Medicaid for health coverage. The phenotypes of SCD represented in this sample were similar to those in the general SCD population. Over 26 months, 39 families received at least one home visit. Parents of infants (younger than 8 months) were more likely to participate in the home-based education program than parents of older children, (Fisher’s exact test, p < .001). CONCLUSIONS: For participating families, home-based visits were a feasible method for reinforcing clinic education. About 43% of eligible families participated in the education, a two-fold increase in the poor attendance (20%) for a previous hospital-based program. A home visitation program for parents of infants with SCD could offer an effective approach to helping these children overcome adverse environmental conditions that are compounded by the complexities of a chronic health condition

Symptom management care pathway adaptation process and specific adaptation decisions

BACKGROUND: There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions. METHODS: Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications. RESULTS: Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection. CONCLUSIONS: Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1

Engaging caregivers and providers of children with sickle cell anemia in shared decision making for hydroxyurea: Protocol for a multicenter randomized controlled trial

BACKGROUND: Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months. However, the uptake remains suboptimal, likely because caregivers lack information about hydroxyurea and have concerns about its safety and potential long-term side effects. Moreover, clinicians do not routinely receive training or tools, especially those that provide medical evidence and consider caregivers\u27 preferences and values, to facilitate a shared discussion with caregivers. OBJECTIVE: The aim of this study is to understand how best to help parents of young children with sickle cell disease and their clinicians have a shared discussion about hydroxyurea (one that considers medical evidence and parent values and preferences). METHODS: We designed our study to compare the effectiveness of two methods for disseminating hydroxyurea guidelines to facilitate SDM: a clinician pocket guide (ie, usual care) and a clinician hydroxyurea SDM toolkit (H-SDM toolkit). Our primary outcomes are caregiver reports of decisional uncertainty and knowledge of hydroxyurea. The study also assesses the number of children (aged 0-5 years) who were offered and prescribed hydroxyurea and the resultant health outcomes. RESULTS: The Ethics Committee of the Cincinnati Children\u27s Hospital Medical Center approved this study in November 2017. As of February 2021, we have enrolled 120 caregiver participants. CONCLUSIONS: The long-term objective of this study is to improve the quality of care for children with SCA. Using multicomponent dissemination methods developed in partnership with key stakeholders and designed to address barriers to high-quality care, caregivers of patients with SCA can make informed and shared decisions about their health. TRIAL REGISTRATION: ClinicalTrials.gov NCT03442114; https://clinicaltrials.gov/ct2/show/NCT03442114. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/27650

Electronic health record-embedded individualized pain plans for emergency department treatment of vaso-occlusive episodes in adults with sickle cell disease: Protocol for a preimplementation and postimplementation study

BACKGROUND: Individuals living with sickle cell disease often require aggressive treatment of pain associated with vaso-occlusive episodes in the emergency department. Frequently, pain relief is poor. The 2014 National Heart, Lung, and Blood Institute evidence-based guidelines recommended an individualized treatment and monitoring protocol to improve pain management of vaso-occlusive episodes. OBJECTIVE: This study will implement an electronic health record-embedded individualized pain plan with provider and patient access in the emergency departments of 8 US academic centers to improve pain treatment for adult patients with sickle cell disease. This study will assess the overall effects of electronic health record-embedded individualized pain plans on improving patient and provider outcomes associated with pain treatment in the emergency department setting and explore barriers and facilitators to the implementation process. METHODS: A preimplementation and postimplementation study is being conducted by all 8 sites that are members of the National Heart, Lung, and Blood Institute-funded Sickle Cell Disease Implementation Consortium. Adults with sickle cell disease aged 18 to 45 years who had a visit to a participating emergency department for vaso-occlusive episodes within 90 days prior to enrollment will be eligible for inclusion. Patients will be enrolled in the clinic or remotely. The target analytical sample size of this study is 160 patient participants (20 per site) who have had an emergency department visit for vaso-occlusive episode treatment at participating emergency departments during the study period. Each site is expected to enroll approximately 40 participants to reach the analytical sample size. The electronic health record-embedded individualized pain plans will be written by the patient\u27s sickle cell disease provider, and sites will work with the local informatics team to identify the best method to build the electronic health record-embedded individualized pain plan with patient and provider access. Each site will adopt required patient and provider implementation strategies and can choose to adopt optional strategies to improve the uptake and sustainability of the intervention. The study is informed by the Technology Acceptance Model 2 and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Provider and patient baseline survey, follow-up survey within 96 hours of an emergency department vaso-occlusive episode visit, and selected qualitative interviews within 2 weeks of an emergency department visit will be performed to assess the primary outcome, patient-perceived quality of emergency department pain treatment, and additional implementation and intervention outcomes. Electronic health record data will be used to analyze individualized pain plan adherence and additional secondary outcomes, such as hospital admission and readmission rates. RESULTS: The study is currently enrolling study participants. The active implementation period is 18 months. CONCLUSIONS: This study proposes a structured, framework-informed approach to implement electronic health record-embedded individualized pain plans with both patient and provider access in routine emergency department practice. The results of the study will inform the implementation of electronic health record-embedded individualized pain plans at a larger scale outside of Sickle Cell Disease Implementation Consortium centers. TRIAL REGISTRATION: ClinicalTrials.gov NCT04584528; https://clinicaltrials.gov/ct2/show/NCT04584528. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24818

Evaluation and implications of natural product use in preoperative patients: a retrospective review

Background: Medication Reconciliation and Medication Safety are two themes emphasized in a variety of healthcare organizations. As a result, health care facilities have established methods for obtaining a patient's medication history. However, these methods may vary among institutions or even among the health care professionals in a single institution, and studies have shown that patients are reluctant to disclose their complementary and alternative medicine use to any health care professional. This lack of disclosure is important in surgical patients because of potential herbal interactions with medications and drugs used during the surgical procedure; and the potential for adverse reactions including effects on coagulation, blood pressure, sedation, electrolytes or diuresis. Therefore, the objectives of this study are to identify patterns of natural product use, to identify potential complications among patients scheduled for surgery, to improve existing medication reconciliation efforts, and to develop discontinuation guidelines for the use of these products prior to surgery. Methods: A retrospective review of surgery patients presenting to the Anesthesia Preoperative Evaluation Clinic (APEC) at the University of Kansas Hospital was conducted to identify the prevalence of natural product use. The following data was collected: patient age; gender; allergy information; date of medication history; number of days prior to surgery; source of medication history; credentials of person obtaining the history; number and name of prescription medications, over-the-counter medications and natural products; and natural product dosage. Following the collection of data and analysis of the most common natural products used, possible complications and interactions were identified, and a protocol regarding the pre-operative use of natural products was developed and implemented. Results: Approximately one-fourth of patients seen in the APEC indicated the use of natural products. Patients taking natural products were significantly older, were more likely to undergo cardiac or chest surgery, and were more likely to be taking more prescription and non-prescription medications (all p < 0.001). Conclusion: Based on the results of this study, it is concluded that there is a need for established guidelines regarding discontinuation of selected natural products prior to surgery and further education is needed concerning the perioperative implications of natural products

Mitochondrial Pyruvate Carriers are not Required for Adipogenesis but are Regulated by High-Fat Feeding in Brown Adipose Tissue

© 2020 The Obesity Society. Objective: The objectives of this study were to assess the role of mitochondrial pyruvate carriers (MPCs) in adipocyte development in vitro and determine whether MPCs are regulated in vivo by high-fat feeding in male and female C57BL/6J mice. Methods: This study utilized small interfering RNA-mediated knockdown to assess the requirement of MPC1 for adipogenesis in the 3T3-L1 model system. Treatment with UK-5099, a potent pharmacological MPC inhibitor, was also used to assess the loss of MPC activity. Western blot analysis was performed on adipose tissue samples from mice on a low-fat diet or a high-fat diet (HFD) for 12 weeks. Results: The loss of MPC expression via small interfering RNA-mediated knockdown or pharmacological inhibition did not affect adipogenesis of 3T3-L1 cells. In vivo studies indicated that expression of MPCs was significantly decreased in brown adipose tissue of male mice, but not female, on an HFD. Conclusions: Although MPCs are essential for pyruvate transport, MPCs are not required for adipogenesis in vitro, suggesting that other substrates can be used for energy production when the MPC complex is not functional. Also, a significant decrease in MPC1 and 2 expression occurred in brown fat, but not white fat, of male mice fed an HFD

Keeping Weight Off: study protocol of an RCT to investigate brain changes associated with mindfulness-based stress reduction

INTRODUCTION: Obesity is a growing epidemic fuelled by unhealthy behaviours and associated with significant comorbidities and financial costs. While behavioural interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. This may partially be due to failure to target stress and emotional reactivity. Mindfulness-based stress reduction (MBSR) reduces stress and emotional reactivity and may be a useful tool for behaviour change maintenance. This study seeks to provide a mechanistic understanding for clinical trials of the benefits of MBSR for weight loss maintenance by examining changes in functional connectivity (FC) and the association of these changes with clinical outcomes. METHODS AND ANALYSIS: Community-dwelling individuals (n=80) who intentionally lost \u3e /=5% of their body weight in the past year will be recruited and randomised to an MBSR programme or educational control. FC using resting-state functional MRI will be measured at baseline and 8 weeks. Psychological factors, health behaviours, body mass index and waist circumference will be measured at baseline, 8 weeks and 6 months post intervention. A 12-month telephone follow-up will assess self-reported weight. Analyses will characterise FC changes in response to MBSR in comparison with a control condition, assess the relationship between baseline FC status and pre-post MBSR changes in FC and investigate the association of FC change with changes in psychological factors and weight loss maintenance. ETHICS AND DISSEMINATION: The University of Massachusetts Medical School Institutional Review Board has approved this study, Declaration of Helsinki protocols are being followed, and patients will give written informed consent. The Independent Monitoring Committee will monitor protocol adherence. Results from the study will be disseminated to the medical community at conferences and submitted for publication in peer-reviewed journals when the last patient included has been followed up for 12 months. TRIAL REGISTRATION NUMBER: NCT02189187