Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease.
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ABSTRACT:
SUBMITTER: Chonat S
PROVIDER: S-EPMC5720159 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease.
Chonat Satheesh S Quinn Charles T CT
Advances in experimental medicine and biology 20170101
Thalassemia and sickle cell disease (SCD) are disorders of hemoglobin that affect millions of people worldwide. The carrier states for these diseases arose as common, balanced polymorphisms during human history because they afforded protection against severe forms of malaria. These complex, multisystem diseases are reviewed here with a focus on current standards of clinical management and recent research findings. The importance of a comprehensive, multidisciplinary and lifelong system of care i ...[more]
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Project description:BackgroundThere are sparse data on the long-term and late effects of hematopoietic cell transplantation (HCT) for sickle cell disease (SCD).ObjectiveThis study aims to establish an international registry of long-term outcomes post-HCT for SCD and demonstrate the feasibility of recruitment at a single site in the United States.MethodsThe Sickle Cell Transplantation Evaluation of Long-Term and Late Effects Registry (STELLAR) was designed to enroll patients with SCD ≥1 year post-HCT, their siblings without SCD, and nontransplanted controls with SCD to collect web-based participant self-reports of health status and practices by using the Bone Marrow Transplant Survivor Study (BMTSS) surveys, health-related quality of life (HRQOL) using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Profile-25 or Pediatric Profile-29 survey, chronic graft-versus-host disease (cGVHD) using the symptom scale survey, daily pain using an electronic pain diary, the economic impact of HCT using the financial hardship survey, sexual function using the PROMIS Sexual Function SexFSv2.0 survey, and economic productivity using the American Time Use Survey (ATUS). We also piloted retrieval of clinical data previously submitted to the Center for International Blood and Marrow Transplant Research (CIBMTR); recorded demographics, height, weight, blood pressure, waist and hip circumferences, timed up and go (TUG) test, and handgrip test; and obtained blood for metabolic screening, gonadal function, fertility potential, and biorepository of plasma, serum, RNA, and DNA.ResultsOf 100 eligible post-HCT patients, we enrolled 72 (72%) participants aged 9-38 (median 17) years. We also enrolled 19 siblings aged 5-32 (median 10) years and 28 nontransplanted controls with SCD aged 4-46 (median 22) years. Of the total 119 participants, 73 (61%) completed 85 sets of surveys and 41 (35%) contributed samples to the biorepository. We completed ATUS interviews of 28 (24%) participants. We successfully piloted retrieval of data submitted to the CIBMTR and expanded recruitment to multiple sites in the United States, Canada, the United Kingdom, and Nigeria.ConclusionsIt is feasible to recruit subjects and conduct study procedures for STELLAR in order to determine the long-term and late effects of HCT for SCD.International registered report identifier (irrid)DERR1-10.2196/36780.
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Project description:Chronic pain affects one-half of adults with sickle cell disease (SCD). Despite the prevalence of chronic pain, few studies have been performed to determine the best practices for this patient population. Although the pathophysiology of chronic pain in SCD may be different from other chronic pain syndromes, many of the guidelines outlined in the pain literature and elsewhere are applicable; some were consensus-adopted in the 2014 National Heart, Lung, and Blood Institute SCD Guidelines. Recommended practices, such as controlled substance agreements and monitoring of urine, may seem unnecessary or counterproductive to hematologists. After all, SCD is a severe pain disorder with a clear indication for opioids, and mistrust is already a major issue. The problem, however, is not with a particular disease but with the medicines, leading many US states to pass broad legislation in attempts to curb opioid misuse. These regulations and other key tenets of chronic pain management are not meant to deprive adults with SCD of appropriate therapies, and their implementation into hematology clinics should not affect patient-provider relationships. They simply encourage prudent prescribing practices and discourage misuse, and should be seen as an opportunity to more effectively manage our patient's pain in the safest manner possible. In line with guideline recommendations as well as newer legislation, we present five lessons learned. These lessons form the basis for our model to manage chronic pain in adults with SCD.
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Project description:Considerable progress with respect to donor source has been achieved in allogeneic stem cell transplant for patients with hemoglobin disorders, with matched sibling donors in the 1980s, matched unrelated donors and cord blood sources in the 1990s, and haploidentical donors in the 2000s. Many studies have solidified hematopoietic progenitors from matched sibling marrow, cord blood, or mobilized peripheral blood as the best source-with the lowest graft rejection and graft versus host disease (GvHD), and highest disease-free survival rates. For patients without HLA-matched sibling donors, but who are otherwise eligible for transplant, fully allelic matched unrelated donor (8/8 HLA-A, B, C, DRB1) appears to be the next best option, though an ongoing study in patients with sickle cell disease will provide data that are currently lacking. There are high GvHD rates and low engraftment rates in some of the unrelated cord transplant studies. Haploidentical donors have emerged in the last decade to have less GvHD; however, improvements are needed to increase the engraftment rate. Thus the decision to use unrelated cord blood units or haploidentical donors may depend on the institutional expertise; there is no clear preferred choice over the other. Active research is ongoing in expanding cord blood progenitor cells to overcome the limitation of cell dose, including the options of small molecule inhibitor compounds added to ex vivo culture or co-culture with supportive cell lines. There are inconsistent data from using 7/8 or lower matched unrelated donors. Before routine use of these less matched donor sources, work is needed to improve patient selection, conditioning regimen, GvHD prophylaxis, and/or other strategies.
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Project description:Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality.This is an update of a Cochrane review first published in 2011 and updated in 2014.We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events.We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. Date of the last search: 25 April 2016.We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 26 January 2016), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 26 January 2016.We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sß(0), SC, or Sß(+) that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension).We used the standard methodological procedures expected by Cochrane.No studies matching the selection criteria were found.There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention.
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Project description:OBJECTIVES:To assess current knowledge of National Heart, Lung and Blood Institutes (NHLBI) and Thalassemia International Federation (TIF) recommendations, blood banking practices and perceived challenges among transfusion services in the management of patients with haemoglobinopathies. BACKGROUND:Previous reports have demonstrated variations in transfusion practices for sickle cell disease (SCD) and thalassemia patients. Recently, NHLBI/TIF have provided transfusion recommendations for patients with haemoglobinopathies. METHODS:A cross-sectional survey was conducted of transfusion services from the state of Georgia previously identified as having SCD/thalassemia populations. The survey assessed transfusion service practices in pre-transfusion testing and blood product selection; awareness/implementation of NHLBI/TIF transfusion-based recommendations and perceived challenges in transfusing haemoglobinopathy patients. RESULTS:Responses were received from 35 of 49 (71%) institutions. Only institutions indicating transfusing SCD or thalassemia patients (32) were included in analysis. Seventy-one percent of non-sickle cell treatment centres (SCTCs) and 20% of non-thalassemia treatment centres follow NHLBI and TIF recommendations to perform a red blood cell phenotype beyond ABO/Rh(D) and provide Rh and Kell prophylactically matched units for SCD and thalassemia patients, respectively. Forty percent of institutions (33% of non-SCTCs) employ RBC genotyping to evaluate the red cell phenotype for SCD patients. Over 77% of institutions do not utilise a reliable method to identify SCD patients prior to transfusion, such as a required question/answer field on type/screen or crossmatch orders. CONCLUSION:Many healthcare systems' transfusion practices for haemoglobinopathy patients are discordant with NHLBI/TIF recommendations. Efforts are needed to increase awareness and implementation of current recommendations among all transfusion services seeing these patients.
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Project description: Not available
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Project description:Sickle cell disease (SCD)-associated nephropathy is a major source of morbidity and mortality in patients because of the lack of efficacious treatments targeting renal manifestations of the disease. Here, we describe a long-term treatment strategy with the selective endothelin-A receptor (ETA) antagonist, ambrisentan, designed to interfere with the development of nephropathy in a humanized mouse model of SCD. Ambrisentan preserved GFR at the level of nondisease controls and prevented the development of proteinuria, albuminuria, and nephrinuria. Microscopy studies demonstrated prevention of podocyte loss and structural alterations, the absence of vascular congestion, and attenuation of glomerulosclerosis in treated mice. Studies in isolated glomeruli showed that treatment reduced inflammation and oxidative stress. At the level of renal tubules, ambrisentan treatment prevented the increased excretion of urinary tubular injury biomarkers. Additionally, the treatment strategy prevented tubular brush border loss, diminished tubular iron deposition, blocked the development of interstitial fibrosis, and prevented immune cell infiltration. Furthermore, the prevention of albuminuria in treated mice was associated with preservation of cortical megalin expression. In a separate series of identical experiments, combined ETA and ETB receptor antagonism provided only some of the protection observed with ambrisentan, highlighting the importance of exclusively targeting the ETA receptor in SCD. Our results demonstrate that ambrisentan treatment provides robust protection from diverse renal pathologies in SCD mice, and suggest that long-term ETA receptor antagonism may provide a strategy for the prevention of renal complications of SCD.
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Project description:BackgroundCaring for older persons has become a global necessity to ensure functional ability and healthy ageing. It is of paramount importance that standards of care are monitored, especially for older persons who live in long term care facilities (LTCF). We, therefore, scoped and summarised evidence relating to standards and the quality of care for older persons in LTCFs in gerontological literature globally.MethodsWe conducted a scoping review using Askey and O'Malley's framework, including Levac et al. recommendations. PubMed, CINAHL, Health Sources, Scopus, Cochrane Library, and Google Scholar were searched with no date limitation up to May 2020 using keywords, Boolean terms, and medical subject headings. We also consulted the World Health Organization website and the reference list of included articles for evidence sources. This review also included peer-reviewed publications and grey literature in English that focused on standards and quality of care for older residents in LTCFs. Two reviewers independently screened the title, abstract, and full-text of evidence sources screening stages and performed the data extraction. Thematic content analysis was used, and a summary of the findings are reported narratively.ResultsSixteen evidence sources published from 1989 to 2017 met this study's eligibility criteria out of 73,845 citations obtained from the broader search. The majority of the studies were conducted in the USA 56% (9/16), and others were from Canada, Hong Kong, Ireland, Norway, Israel, Japan, and France. The included studies presented evidence on the effectiveness of prompted voiding intervention for urinary incontinence in LTCFs (37.5%), the efficacy of professional support to LTCF staff (18.8%), and the prevention-effectiveness of a pressure ulcer programme in LTCFs (6.3%). Others presented evidence on regulation and quality of care (12.5%); nursing documentation and quality of care (6.3%); medical, nursing, and psychosocial standards on the quality of care (6.3%); medication safety using the Beer criteria (6.3%); and the quality of morning care provision (6.3%).ConclusionThis study suggests most studies relating to standards and quality of care in LTCFs focus on effectiveness of interventions, few on people-centredness and safety, and are mainly conducted in European countries and the United States of America. Future studies on people-centerdness, safety, and geographical settings with limited or no evidence are recommended.
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