Sickle cell anemia is an inherited blood disorder that is characterized by painful vaso-occlusive crises, for which there are few treatment options. Platelets mediate intercellular adhesion and ...thrombosis during vaso-occlusion in sickle cell anemia, which suggests a role for antiplatelet agents in modifying disease events.
Children and adolescents 2 through 17 years of age with sickle cell anemia were randomly assigned to receive oral prasugrel or placebo for 9 to 24 months. The primary end point was the rate of vaso-occlusive crisis, a composite of painful crisis or acute chest syndrome. The secondary end points were the rate of sickle cell-related pain and the intensity of pain, which were assessed daily with the use of pain diaries.
A total of 341 patients underwent randomization at 51 sites in 13 countries across the Americas, Europe, Asia, and Africa. The rate of vaso-occlusive crisis events per person-year was 2.30 in the prasugrel group and 2.77 in the placebo group (rate ratio, 0.83; 95% confidence interval, 0.66 to 1.05; P=0.12). There were no significant differences between the groups in the secondary end points of diary-reported events. The safety end points, including the frequency of bleeding events requiring medical intervention, of hemorrhagic and nonhemorrhagic adverse events that occurred while patients were taking prasugrel or placebo, and of discontinuations due to prasugrel or placebo, did not differ significantly between the groups.
Among children and adolescents with sickle cell anemia, the rate of vaso-occlusive crisis was not significantly lower among those who received prasugrel than among those who received placebo. There were no significant between-group differences in the safety findings. (Funded by Daiichi Sankyo and Eli Lilly; ClinicalTrials.gov number, NCT01794000.).
Background
Sickle cell disease (SCD) and thalassemia are inherited blood disorders, which can lead to life-threatening events and chronic organ damage. Recent advances in treatments have increased ...life expectancy, and hemoglobinopathies have become chronic illnesses with social and emotional impairments. Thus, health-related quality of life (HRQOL) assessment has a fundamental role in disease management and treatment, and generic and disease-specific questionnaires are reliable and validated measures to estimate disease burden. The heterogeneous distribution of treatment opportunities worldwide influences physical, social, and emotional disease perception.
Objectives
To review publications concerning HRQOL for SCD and thalassemia in different areas of the world in order to gather a global perspective of questionnaires used and outcomes evaluated.
Methods
A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Medline databases were searched on 29 September 2021. Inclusion criteria were as follows: (1) studies of HRQOL assessment in SCD and thalassemia patients by using the PROMIS, the SF-36, the SCSES, the PedsQL-SCD, the PedsQOL generic core scale, the ASCQ-Me, and the TranQoL; and (2) every article type, including non-English studies. We excluded studies that were not limited to SCD or thalassemia and studies that were not specific to hemoglobinopathies, and not consistent with the topic of HRQOL assessment. We did not include the gray literature. A total of 102 out of 124 articles from PubMed, Cochrane Library, and Google Scholar were eligible for inclusion (66 SCD articles and 36 thalassemia articles). The quality of studies was assessed through Critical Appraisal tools for use in JBI Systematic Reviews. Data extraction was conducted using a standardized data collection form (authors, year and country of publication, study design, age and number of patients, HRQOL questionnaires, questionnaire language, and clinical outcomes).
Results
The evaluation of HRQOL was conducted on all continents, but differences in the worldwide frequency of HRQOL assessment were observed. HRQOL of SCD patients was less investigated in Europe. HRQOL of thalassemia patients was less investigated in South-East Asia and Africa. Generic HRQOL questionnaires (PROMIS, SF-36, and PedsQL) were frequently adopted, while disease-specific ones (ASCQ-Me, SCSES for SCD, and TranQoL for thalassemia) were less used. Translation into local languages has been often performed.
Conclusion
Health-related quality of life is a complex outcome that has been increasingly incorporated in clinical research and clinical practice worldwide, although with regional differences. Disease-specific outcomes (pain for SCD and transfusion burden for thalassemia) and healthcare system characteristics, particularly in low-income countries, have an impact on HRQOL and should be considered in healthcare plans.
The objective of the present article is to highlight the need for attention to Quality of Life of patients with Sickle Cell Disease living in Italy. The transformation of sickle cell disease from a ...severe life-threatening disease of childhood into a chronic, lifelong condition due to the significant improvements in care and treatment options, imposes increasing new challenges to health care providers and patients. Patients now face physical, psychosocial and emotional challenges throughout their lives. They generally have to receive chronic treatments and regular multidisciplinary monitoring which increase social and emotional burden rendering adherence to treatment sometimes complicated. A chronic disease impacts all aspects of patients' lives, not only the physical one, but also the social and emotional aspects as well as the educational and working life. The entire "Quality of Life" is affected and recent evidence demonstrates the importance quality of life has for patients with chronic illness. The results of this review focus on emerging data regarding quality of life across the lifespan of patients with Sickle Cell Disease, and highlight the need for more action in this field in Italy, where recent immigration and improved care determine an increasing population of children with sickle cell disease being taken into long term care.
Sickle cell disease (SCD) is a severe hereditary blood disorder caused by a mutation of the beta-globin gene, which results in a substantial reduction in life expectancy. Many studies are focused on ...various novel therapeutic strategies that include re-activation of the
γ
-globin gene. Among them, expression therapy caused by the fetal hemoglobin (HbF) at a later age is highly successful. The induction of HbF is one of the dominant genetic modulators of the hematological and clinical characteristics of SCD. In fact, HbF compensates for the abnormal beta chain and has an ameliorant effect on clinical complications. Erythropoiesis is a multi-step process that involves the proliferation and differentiation of a small population of hematopoietic stem cells and is affected by several factors, including signaling pathways, transcription factors, and small non-coding RNAs (miRNAs). miRNAs play a regulatory role through complex networks that control several epigenetic mechanisms as well as the post-transcriptional regulation of multiple genes. In this review, we briefly describe the current understanding of interactions between miRNAs, their molecular targets, and their regulatory effects in HbF induction in SCD.
Sickle cell disease (SCD) is an inherited monogenic disorder with high prevalence throughout sub-Saharan Africa, the Mediterranean basin, the Middle East, and India. Sources of SCD epidemiology ...remain scarce and fragmented. A systematic literature review (SLR) to identify peer-reviewed studies on SCD epidemiology was performed, with a search of bibliographic databases and key conference proceedings from 1 January 2010 to 25 March 2022 (congress abstracts after 2018). The SLR followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Meta-analyses, using a binomial normal random-effects model, were performed to estimate global and regional prevalence and birth prevalence. Of 1770 journal articles and 468 abstracts screened, 115 publications met the inclusion criteria. Prevalence was highest in Africa (~800/100,000), followed by the Middle East (~200/100,000) and India (~100/100,000), in contrast to ~30/100,000 in Europe. Birth prevalence was highest in Africa (~1000/100,000) and lowest in North America (~50/100,000) and Europe (~30/100,000). This SLR confirmed that sub-Saharan and North-East Africa, India, the Middle East, and the Caribbean islands are global SCD hotspots. Publications including mortality data were sparse, and no conclusions could be drawn about mortality. The identified data were limited due to gaps in the published literature for large parts of the world population; the inconsistent reporting of SCD genotypes, diagnostic criteria, and settings; and a sparsity of peer-reviewed publications from countries with assumed high prevalence. This SLR demonstrated a lack of systematic knowledge and a need to provide uniform data collection on SCD prevalence and mortality.
Oral ferrous salts are standard treatment for children with iron deficiency anemia (IDA). The objective of our study was to monitor oral iron therapy in children, aged 3 months–12 years, with IDA. We ...prospectively collected clinical and hematological data of children with IDA, from 15 AIEOP (Associazione Italiana di Ematologia ed. Oncologia Pediatrica) centers. Response was measured by the increase of Hb from baseline. Of the 107 analyzed patients, 18 received ferrous gluconate/sulfate 2 mg/kg (ferrous 2), 7 ferrous gluconate/sulfate 4 mg/kg (ferrous 4), 7 ferric iron salts 2 mg/kg (ferric), 62 bis-glycinate iron 0.45 mg/kg (glycinate), and 13 liposomal iron 0.7–1.4 mg/kg (liposomal). Increase in reticulocytes was evident at 3 days, while Hb increase appeared at 2 weeks. Gain of Hb at 2 and 8 weeks revealed a higher median increase in both ferrous 2 and ferrous 4 groups. Gastro-intestinal side effects were reported in 16% (ferrous 2), 14% (ferrous 4), 6% (glycinate), and 0 (ferric and liposomal) patients. The reticulocyte counts significantly increased after 3 days from the start of oral iron supplementation. Bis-glycinate iron formulation had a good efficacy/safety profile and offers an acceptable alternative to ferrous iron preparations.
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