Elevated Circulating Angiogenic Progenitors and White Blood Cells Are Associated with Hypoxia-Inducible Angiogenic Growth Factors in Children with Sickle Cell Disease

We studied the number and function of angiogenic progenitor cells and growth factors in children aged 5–18 years without acute illness, 43 with Hemoglobin SS and 68 with normal hemoglobin. Hemoglobin SS subjects had at least twice as many mononuclear cell colonies and more circulating progenitor cell than Control subjects. Plasma concentrations of erythropoietin, angiopoietin-2, and stromal-derived growth factor (SDF)-1α were significantly higher in children with Hemoglobin SS compared to Control subjects. In a multivariate analysis model, SDF-1α concentration was found to be associated with both CPC number and total white blood cell count in the Hemoglobin SS group, suggesting that SDF-1α produced by ischemic tissues plays a role in mobilizing these cells in children with Hemoglobin SS. Despite having a higher number of angiogenic progenitor cells, children with Hemoglobin SS had slower migration of cultured mononuclear cells

IMPROVE trial: A randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies

BACKGROUND: The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Although ambulatory pain accounts for most days in pain, pain is also the most common cause of hospitalization and is typically treated with parenteral opioids. The evidence base is lacking for most analgesic practice in SCD, particularly for the optimal opioid dosing for patient-controlled analgesia (PCA), in part because of the challenges of the trial design and conduct for this rare disease. PURPOSE: The purpose of this report is to describe our Network's experiences with protocol development, implementation, and analysis, including overall study design, the value of pain assessments rather than 'crisis' resolution as trial endpoints, and alternative statistical analysis strategies. METHODS: The Improving Pain Management and Outcomes with Various Strategies (IMPROVE) PCA trial was a multisite inpatient randomized controlled trial comparing two PCA-dosing strategies in adults and children with SCD and acute pain conducted by the SCD Clinical Research Network. The specified primary endpoint was a 25-mm change in a daily average pain intensity using a Visual Analogue Scale, and a number of related pain intensity and pain interference measures were selected as secondary efficacy outcomes. A time-to-event analysis strategy was planned for the primary endpoint. RESULTS: Of 1116 individuals admitted for pain at 31 participating sites over a 6-month period, 38 were randomized and 4 withdrawn. The trial was closed early due to poor accrual, reflecting a substantial number of challenges encountered during trial implementation. LIMITATIONS: While some of the design issues were unique to SCD or analgesic studies, many of the trial implementation challenges reflected the increasing complexity of conducting clinical trials in the inpatient setting with multiple care providers and evolving electronic medical record systems, particularly in the context of large urban academic medical centers. LESSONS LEARNED: Complicated clinical organization of many sites likely slowed study initiation. More extensive involvement of research staff and site principal investigator in the clinical care operations improved site performance. During the subsequent data analysis, alternative statistical approaches were considered, the results of which should inform future efficacy assessments and increase future trial recruitment success by allowing substantial reductions in target sample size. CONCLUSIONS: A complex randomized analgesic trial was initiated within a multisite disease network seeking to provide an evidence base for clinical care. A number of design considerations were shown to be feasible in this setting, and several pain intensity and pain interference measures were shown to be sensitive to time- and treatment-related improvements. While the premature closure and small sample size precluded definitive conclusions regarding treatment efficacy, this trial furnishes a template for design and implementation considerations that should improve future SCD analgesic trials

Sickle Cell Diseae Program Children's Healthcare of Atlanta

Presented on June 23, 2011 from 2:00 pm to 5:30 pm, Klaus 1116E on the Georgia Tech Campus.Runtime: 14:09 minute

Patient Perception on Health Care Delivery for Sickle Cell Disease and Opportunities for Quality Improvement

The Health Resources and Services (HRSA)-sponsored Sickle Cell Disease (SCD)Treatment Demonstration Regional Collaborative Program, EMBRACE SCD Florida has three aims: 1. To educate providers about SCD, 2. To assess patients' perception on health care and barriers encountered, and 3. To increase hydroxyurea (HU) treatment as disease-modifying therapy. We report the patients' perception on health care delivery as assessed by surveys of 65 patients at two SCD centers in South Florida. All participants signed the IRB-approved informed consent/assent and completed a 46-question survey. Surveys addressed patient demographics, HU use, pain experienced, facility utilization and confidence in SCD doctors and primary care providers (PCPs). Parents represented 62 % of the sample respondents. There were 37 female and 28 male patients, with a mean age of 14.8 years, median 12 years (range 1-45). Patients were self-identified as SS (N=42, 65%), SC (N=8), sickle-β+ thalassemia (N=5), sickle-β0 thalassemia (N=2), other (N=1), and 7 (11%) did not know their genotype. Most (55%) were African-Americans; 26% Haitians, 12% Black non-African-American or other, and 6% were White. Nine percent were Hispanic. Insurance coverage was identified as Medicaid (75%), Managed Care Organization (7%), Medicare (13%), and private insurance (5%). Of the 44 patients with SS and Sβ0, 84% (N=37) received medical advice to take HU from SCD provider. In addition, 12 patients (4 unknown type, 5 Sβ+ and 3 SC) were advised to take HU for a total of 49 or 75% of all patients surveyed. Seventy-eight percent (N=38) of those agreed to be treated, and 22% (N=11) declined HU. Eighty-four percent of those who agreed to be treated (N=32) reported taking HU as prescribed. Those patients who have received HU identified many barriers: lack of money to pay (N=5), nausea (N=5), hair loss (N=1), do not like the taste (N=8), do not like to take medications so they either do not take it frequently (N=7) or force themselves to take it (N=12), lack of effectiveness for their pain (N=10), and forgetting to take HU (N=18). Eighteen of 49 (37%) said they had no problems taking HU. We asked all patients about their pain experience. Of the 63 who responded, 30 (47.6%) said pain was managed well all the time, whereas the rest perceived difficulties in pain management: 20 (31.7%), 12 (19%), and one (1.6%) perceived their pain was managed well 75% of time, 50% of the time, and 25% or less of the time, respectively. The frequency of taking pain medications was variable among patients. The most common frequency of taking pain medications was several times a month (24 of 63 or 38%), but ranged from taking pain medication daily (N=9, 14%) to never or almost never (N=10, 16%). The emergency room (ER) was the first place they would go to when they get sick. One patient reported he prefers staying home. Patients reported a median of two ER visits (range 0-45) and two hospitalizations (range 0-30) in the previous 12 months. Almost all (92%) patients reported having a PCP. Sixty-seven percent visited the PCP 1-3 times per year, whereas 88% visited the SCD doctor 4-12 times per year. Whereas 68.3% patients trusted their PCP to manage their SCD, their level of trust with the SCD doctor was 95.2% (p <0.01). Similarly, 68% patients agreed that both the PCP and the SCD doctor should share responsibilities in their care. The table shows what participants considered most important for their PCP and their SCD doctor to know or learn about SCD. The most common single thing participants would change about the health care system was insurance/health care coverage (N=7), improved communication with providers (N=4), better care (N=2), or to have a cure for SCD (N=2). Six would not change anything. Eighty-four percent of patients did not know how to contact Sickle Cell Disease of America (SCDAA). Nine patients or parents (14%) felt discriminated against by health providers (N=3, doctors, nurses, pharmacy) and others (N=6, employers, classmates, others) as a result of their SCD. We identified five opportunities for quality improvement: 1. Improve pain control as 52.4% patients viewed their pain was sub-optimally managed, 2. Further examine and decrease barriers for HU treatment, 3. PCP education, as 31.7% of patients lacked trust in their competence, 4. Educate and encourage patient interaction with community-based organizations like SCDAA, and 5. Explore policy change in health care insurance coverage. Table Disclosures Alvarez: Forma Therapeutics: Consultancy; Novartis: Consultancy. Clay:Novartis: Speakers Bureau. Black:NHLBI: Research Funding; Micelle BioPharma: Research Funding; Pfizer: Research Funding; Sancilio and Company: Research Funding; Sanofi: Consultancy; Prolong Pharmaceuticals: Consultancy; Novartis: Research Funding; HRSA: Research Funding. Osunkwo:Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Terumo: Speakers Bureau; Micella Biopharma: Other: DSMB member

Successful quality improvement project to increase hydroxyurea prescriptions for children with sickle cell anaemia

Hydroxyurea (HU) is an effective but underused disease-modifying therapy for patients with sickle cell anaemia (SCA). EMBRACE SCD, a sickle cell disease treatment demonstration project, aimed to improve access to HU by increasing prescription (Rx) rates by at least 10% from baseline in children with SCA.The Model for Improvement was used as the quality improvement framework. HU Rx was assessed from clinical databases in three paediatric haematology centres. Children aged 9 months–18 years with SCA not on chronic transfusions were eligible for HU treatment. The health belief model was the conceptual framework to discuss with patients and promote HU acceptance. A visual aid showing erythrocytes under the effect of HU and the American Society of Hematology HU brochure were used as educational tools. At least 6 months after offering HU, a Barrier Assessment Questionnaire was given to assess reasons for HU acceptance and refusals. If HU was declined, the providers discussed with family again. We conducted chart audits to find missed opportunities to prescribe HU as one plan–do–study–act cycle.At initial measurement, 50.2% of 524 eligible patients had HU prescribed. During the testing and initial implementation phase, the mean performance after 10 data points was 53%. After 2 years, the mean performance was 59%, achieving an 11% increase in mean performance and a 29% increase from initial to the last measurement (64.8% HU Rx). During a 15-month period, 32.1% (N=168) of the eligible patients who were offered HU completed the barrier questionnaire with 19% (N=32) refusing HU, mostly based on not perceiving enough severity of their children’s SCA or fearing side effects.Reviewing patient charts for missed opportunity of offering HU with feedback and evaluating the reasons of declining HU via a questionnaire were key components in increasing HU Rx in our population

Beyond the Definitions of the Phenotypic Complications of Sickle Cell Disease: An Update on Management

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes

Early Patient-Centered Outcomes Research Experience With the Use of Telehealth to Address Disparities: Scoping Review

BackgroundHealth systems and providers across America are increasingly employing telehealth technologies to better serve medically underserved low-income, minority, and rural populations at the highest risk for health disparities. The Patient-Centered Outcomes Research Institute (PCORI) has invested US $386 million in comparative effectiveness research in telehealth, yet little is known about the key early lessons garnered from this research regarding the best practices in using telehealth to address disparities. ObjectiveThis paper describes preliminary lessons from the body of research using study findings and case studies drawn from PCORI seminal patient-centered outcomes research (PCOR) initiatives. The primary purpose was to identify common barriers and facilitators to implementing telehealth technologies in populations at risk for disparities. MethodsA systematic scoping review of telehealth studies addressing disparities was performed. It was guided by the Arksey and O’Malley Scoping Review Framework and focused on PCORI’s active portfolio of telehealth studies and key PCOR identified by study investigators. We drew on this broad literature using illustrative examples from early PCOR experience and published literature to assess barriers and facilitators to implementing telehealth in populations at risk for disparities, using the active implementation framework to extract data. Major themes regarding how telehealth interventions can overcome barriers to telehealth adoption and implementation were identified through this review using an iterative Delphi process to achieve consensus among the PCORI investigators participating in the study. ResultsPCORI has funded 89 comparative effectiveness studies in telehealth, of which 41 assessed the use of telehealth to improve outcomes for populations at risk for health disparities. These 41 studies employed various overlapping modalities including mobile devices (29/41, 71%), web-based interventions (30/41, 73%), real-time videoconferencing (15/41, 37%), remote patient monitoring (8/41, 20%), and store-and-forward (ie, asynchronous electronic transmission) interventions (4/41, 10%). The studies targeted one or more of PCORI’s priority populations, including racial and ethnic minorities (31/41, 41%), people living in rural areas, and those with low income/low socioeconomic status, low health literacy, or disabilities. Major themes identified across these studies included the importance of patient-centered design, cultural tailoring of telehealth solutions, delivering telehealth through trusted intermediaries, partnering with payers to expand telehealth reimbursement, and ensuring confidential sharing of private information. ConclusionsEarly PCOR evidence suggests that the most effective health system- and provider-level telehealth implementation solutions to address disparities employ patient-centered and culturally tailored telehealth solutions whose development is actively guided by the patients themselves to meet the needs of specific communities and populations. Further, this evidence shows that the best practices in telehealth implementation include delivery of telehealth through trusted intermediaries, close partnership with payers to facilitate reimbursement and sustainability, and safeguards to ensure patient-guided confidential sharing of personal health information