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Background: Sickle cell disease (SCD) is an autosomal recessive haemoglobin disorder, affecting about 7.74 million individuals worldwide, but it is more prevalent among Africans and Asians. SCD is characterised by many complications, and it is a major health issue in Nigeria, the country with the largest burden of the disease globally. This work aims to present the design and implementation of electronic registries (ER) for SCD in a tertiary hospital in Nigeria. Methods: Registry design was initiated during a staff exchange programme within the ARISE initiative (EU grant agreement no. 824021). Ethical approval was obtained, and paper records were retrieved and transferred into one adult and one paediatric database, developed with Microsoft Access. Results: Data from 2659 SCD patients were entered in the ERs, including 698 (26.3%) adults and 1961 (73.7%) children. There were 287 (41%) male adults, 404 (58%) female and 7 (1%) patients whose gender was missing. There were 1041 (53.1%) male children, 906 (46.2%) female and 14 (0.7%) whose gender was missing. Information on phenotype was available for 2385 subjects, and most of them (2082, 87.3%) were SS. The most prevalent SCD-related complication was painful events (26.6% in adults and 68.7% in children, considering valid cases). Conclusions: About 60% of SCD patients in the centre were included in the ERs providing useful, hands-on recommendations for future ER design in SCD. These ERs might be an appropriate tool for collecting and analysing SCD patients' data. [ABSTRACT FROM AUTHOR]

Objectives: Sickle cell disease (SCD) is an inherited disorder that causes lifelong complications, substantially impacting the physical and emotional well‐being of patients and their caregivers. Studies investigating the effects of SCD on quality of life (QOL) are often limited to individual countries, lack SCD‐specific QOL questionnaires, and exclude the caregiver experience. The SHAPE survey aimed to broaden the understanding of the global burden of SCD on patients and their caregivers and to capture the viewpoint of healthcare providers (HCPs). Methods: A total of 919 patients, 207 caregivers, and 219 HCPs from 10, 9, and 8 countries, respectively, answered a series of closed‐ended questions about their experiences with SCD. Results: The symptoms most frequently reported by patients were fatigue/tiredness (84%) and pain/vaso‐occlusive crises (71%). Patients' fatigue/tiredness had one of the greatest impacts on both patients' and caregivers' QOL. On average, patients and caregivers reported missing 7.5 days and 5.0 days per month, respectively, of school or work. HCPs reported a need for effective tools to treat fatigue/tiredness and a desire for more support to educate patients on long‐term SCD‐related health risks. Conclusions: The multifaceted challenges identified using the SHAPE survey highlight the global need to improve both patient and caregiver QOL. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the acceptability and safety profile of nocturnal long-term oxygen therapy (LTOT) in children with sickle cell disease (SCD) and chronic hypoxaemia.Design: Retrospective cohort study.Patients, Setting and Intervention: Children with SCD who started LTOT from 2014 to early 2019 in two tertiary hospitals in London, UK were retrospectively enrolled. Patients who started disease-modifying therapies <12 months before LTOT or while on LTOT were excluded.Main Outcome Measures: Minor and major adverse events during LTOT were reported. Laboratory and clinical data, transcranial Doppler (TCD) scans and overnight oximetry studies performed at steady state within 12 months before and after starting LTOT were compared.Results: Nineteen children (10 males; median age 12 years, range 6-15) were included. Nearly half of them (9/19; 47%) were on hydroxyurea at baseline. No child discontinued LTOT because of intolerance or poor adherence. No major adverse events were reported. Laboratory data did not show significant changes in haemoglobin and reticulocyte count after 1 year of follow-up. No statistically significant change in the incidence of vaso-occlusive pain events was noted (median annual rate from 0.5 to 0 episode per patient/year; p=0.062). Overnight oximetry tests performed while on LTOT showed improvements in all oxygen saturation parameters (mean overnight and nadir SpO2, % of time spent with SpO2 <90%) compared with the baseline.Conclusion: LTOT is a safe and feasible treatment option for children with SCD and chronic hypoxaemia. [ABSTRACT FROM AUTHOR]

This article reviews data about transition from paediatric to adult services in patients with sickle cell disease, the most common inherited disease in the UK, and outlines how this has been addressed in a large UK sickle cell centre. [ABSTRACT FROM AUTHOR]

Background: Effective stroke prevention in sickle cell disease (SCD) is recommended for children with sickle cell anaemia. Effective implementation relies on the correct stratification of stroke risk using Transcranial Doppler Ultrasound (TCD), prior to committing children to long-term treatment with transfusion. Nevertheless, less than 50% of children with SCD in Europe receive annual TCD—one of the reasons being a lack of trained personnel. The present European multi-centre study was designed to promote the standardisation and delivery of effective screening. Methods: Fifty-five practitioners from differing professional backgrounds were recruited to the TCD training program. The impact of the training programme was evaluated in three European haematology clinics by comparing stroke risk classification and middle cerebral artery time-averaged maximum velocity (TAMMV) obtained from a cohort of 555 patients, before and after training. Results: 42% (23/55) of trainees successfully completed the program. The TAMMV, used to predict stroke risk at each Centre, demonstrated the highest values in Centre 3 (p < 0.0001) before training. The imaging-TCD TAMMV was also higher in Centre 3 (p < 0.001). Following training, the TAMMV showed closer agreement between centres for both imaging-TCD and non-imaging TCD. The stroke risk distribution of children at each centre varied significantly before training (p < 0.001), but improved after training (Fisher's Exact: no treatment = 5.6, p = 0.41, treatment = 13.8, p < 0.01). The same consistency in stroke risk distribution following training was demonstrated with both non-imaging and imaging-TCD data. Conclusion: The attainment of competency in stroke screening using transcranial Doppler scanning (TCD) in sickle cell disease is more feasible for professionals with an ultrasound imaging background. A quality assurance (QA) system is required to ensure that standards are maintained. Further work is in progress to develop an achievable and reproducible QA program. [ABSTRACT FROM AUTHOR]

The clinical severity of sickle cell disease (SCD) is strongly influenced by the level of fetal haemoglobin (HbF) persistent in each patient. Three major HbF loci (BCL11A, HBS1L-MYB, and Xmn1-HBG2) have been reported, but a considerable hidden heritability remains. We conducted a genome-wide association study for HbF levels in 1006 Nigerian patients with SCD (HbSS/HbSβ0), followed by a replication and meta-analysis exercise in four independent SCD cohorts (3,582 patients). To dissect association signals at the major loci, we performed stepwise conditional and haplotype association analyses and included public functional annotation datasets. Association signals were detected for BCL11A (lead SNP rs6706648, β = -0.39, P = 4.96 × 10-34) and HBS1L-MYB (lead SNP rs61028892, β = 0.73, P = 1.18 × 10-9), whereas the variant allele for Xmn1-HBG2 was found to be very rare. In addition, we detected three putative new trait-associated regions. Genetically, dissecting the two major loci BCL11A and HBS1L-MYB, we defined trait-increasing haplotypes (P < 0.0001) containing so far unidentified causal variants. At BCL11A, in addition to a haplotype harbouring the putative functional variant rs1427407-'T', we identified a second haplotype, tagged by the rs7565301-'A' allele, where a yet-to-be-discovered causal DNA variant may reside. Similarly, at HBS1L-MYB, one HbF-increasing haplotype contains the likely functional small indel rs66650371, and a second tagged by rs61028892-'C' is likely to harbour a presently unknown functional allele. Together, variants at BCL11A and HBS1L-MYB SNPs explained 24.1% of the trait variance. Our findings provide a path for further investigation of the causes of variable fetal haemoglobin persistence in sickle cell disease., (© The Author(s) 2024. Published by Oxford University Press.)

Tonsillectomy and adenoidectomy (T&A) is frequently performed in children with sickle cell disease (SCD). Our aim was to evaluate the impact of this surgery on overnight oxygenation and rates of complications in these patients. Children with SCD who underwent T&A between 2008 and 2014 in two tertiary hospitals were retrospectively evaluated. Overnight oximetry and admission rates due to vaso-occlusive pain episodes (VOEs) and acute chest syndrome (ACS) in the year preceding and following the surgery were compared. 19 patients (10 males, 53%) with a median age of 6 years (range 3.5-8) were included. A significant increase of mean overnight arterial oxygen saturation measured by pulse oximetry ( S ) (from 93±3.6% to 95.3±2.8%, p=0.001), nadir pO 2 (from 83.0±7.1% to 88±4.1%, p=0.004) and a reduction of 3% oxygen desaturation index (from a median value of 5.7 to 1.8, p=0.003) were shown. The mean annual rate of ACS decreased from 0.6±1.22 to 0.1±0.2 events per patient-year (p=0.003), while the mean cumulative rate of hospitalisations for all causes and the incidence of VOEs were not affected. T&A improved nocturnal oxygenation and was also associated with a reduction in the incidence of ACS at 1-year follow-up after surgery.S pO 2 (from 83.0±7.1% to 88±4.1%, p=0.004) and a reduction of 3% oxygen desaturation index (from a median value of 5.7 to 1.8, p=0.003) were shown. The mean annual rate of ACS decreased from 0.6±1.22 to 0.1±0.2 events per patient-year (p=0.003), while the mean cumulative rate of hospitalisations for all causes and the incidence of VOEs were not affected. T&A improved nocturnal oxygenation and was also associated with a reduction in the incidence of ACS at 1-year follow-up after surgery., Competing Interests: Conflict of interest: I. Liguoro has nothing to disclose. Conflict of interest: M. Arigliani has nothing to disclose. Conflict of interest: B. Singh has nothing to disclose. Conflict of interest: L. Van Geyzel has nothing to disclose. Conflict of interest: S. Chakravorty has nothing to disclose. Conflict of interest: C. Bossley has nothing to disclose. Conflict of interest: M. Pelidis has nothing to disclose. Conflict of interest: D. Rees has nothing to disclose. Conflict of interest: B.P.D. Inusa reports educational grants from Novartis plc, AstraZeneca, Cyclerion and Bluebird bio, outside the submitted work. Conflict of interest: A. Gupta has nothing to disclose., (Copyright ©ERS 2020.)

Sickle cell disease (SCD) is a monogenetic disorder due to a single base-pair point mutation in the β-globin gene resulting in the substitution of the amino acid valine for glutamic acid in the β-globin chain. Phenotypic variation in the clinical presentation and disease outcome is a characteristic feature of the disorder. Understanding the pathogenesis and pathophysiology of the disorder is central to the choice of therapeutic development and intervention. In this special edition for newborn screening for haemoglobin disorders, it is pertinent to describe the genetic, pathologic and clinical presentation of sickle cell disease as a prelude to the justification for screening. Through a systematic review of the literature using search terms relating to SCD up till 2019, we identified relevant descriptive publications for inclusion. The scope of this review is mainly an overview of the clinical features of pain, the cardinal symptom in SCD, which present following the drop in foetal haemoglobin as young as five to six months after birth. The relative impact of haemolysis and small-vessel occlusive pathology remains controversial, a combination of features probably contribute to the different pathologies. We also provide an overview of emerging therapies in SCD., Competing Interests: Conflicts of InterestB.P.D.I. receives educational grant from Global Therapeutics, Pfizer, Novartis plc Cyclerion and honorarium from Novartis plc. L.L.H. is a consultant for Hilton Publishing, Pfizer, AstraZeneca, Emmaus, Emmi Solutions, and University of Cincinnati., (© 2019 by the authors.)

Background: Sickle Cell Disease (SCD) has been designated by WHO as a public health problem in sub-Saharan Africa, and the development of newborn screening (NBS) is crucial to the reduction of high SCD morbidity and mortality. Strategies from the field of implementation science can be useful for supporting the translation of NBS evidence from high income countries to the unique cultural context of sub-Saharan Africa. One such strategy is community engagement at all levels of the healthcare system, and a widely-used implementation science framework, "Getting to Outcomes ® " (GTO), which incorporates continuous multilevel evaluation by stakeholders about the quality of the implementation., Objectives: (1) to obtain critical information on potential barriers to NBS in the disparate ethnic groups and settings (rural and urban) in the healthcare system of Kaduna State in Nigeria; and, (2) to assist in the readiness assessment of Kaduna in the implementation of a sustainable NBS programme for SCD., Methods: Needs assessment was conducted with stakeholder focus groups for two days in Kaduna state, Nigeria, in November 2017., Results: The two-day focus group workshop had a total of 52 participants. Asking and answering the 10 GTO accountability questions provided a structured format to understand strengths and weaknesses in implementation. For example, we found a major communication gap between policy-makers and user groups., Conclusion: In a two-day community engagement workshop, stakeholders worked successfully together to address SCD issues, to engage with each other, to share knowledge, and to prepare to build NBS for SCD in the existing healthcare system., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest, (© 2018 by the authors.)

Background: Sickle-cell disease (SCD) is the most common inherited genetic disorder in sub-Saharan Africa, and it is associated with early mortality and lifelong morbidity. Early diagnosis is essential for instituting appropriate care and preventive therapy., Objective: To compare parental knowledge or perception of their offspring's hemoglobin phenotype prior to testing and actual validated laboratory test results., Methods: In a prospective community-based survey, we assessed parental knowledge of their children's hemoglobin phenotype and corroborated this with the results from a laboratory confirmatory test determined by high-performance liquid chromatography., Results: We screened 10,126 children aged less than 5 years. A total of 163 (1.6%) parents indicated that their offspring had been previously tested and had knowledge of the child's hemoglobin genotype. However, 51 (31.2%) of 163 parents of children who had been previously tested did not know the result of their offspring's test, and 18 (35.3%) of these 51 children were found to have SCD. Of those who claimed previous knowledge, 25 (15.3%) of 163 reported incorrect results. Overall, we identified 272 (2.76%) new cases from 9,963 children who had not been previously tested., Conclusion: There is the need to promote public awareness about SCD and the benefit of early diagnosis, quality assurance in laboratory diagnosis and institution of sustainable patient care pathways., (© 2016 S. Karger AG, Basel.)

Background: Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care., Methods: In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct., Results: A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04)., Conclusions: Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).

Background: Sickle cell disease (SCD) is now the most common genetic condition in the world including the UK with an estimate of over 12,500 affected people and over 300 new births per year. Blood transfusion therapy plays a very important role as a disease-modifying strategy in severe SCD e.g. primary and secondary stroke prevention and other acute life-threatening complications such as acute chest infections and acute multi-organ failure. Blood transfusion, however, carries a number of risks including alloimmunisation. There is the need to increase the level of awareness and education about SCD and also to increase blood donation drive among affected communities. These communities are mostly ethnic minority populations who are recognised to have poor access to health care services. Due to the strong impact of religion on these populations, faith organisations may provide potential access for health promotion and interventions., Methods: A literature search was conducted to find studies published between 1990-2008 aimed at examining the influence of religious leaders and faith organisations in health, with particular reference to haemoglobinopathies., Results: Eleven studies were reviewed covering a variety of health interventions. The findings suggest that involvement of religious leaders and faith organisations in health related interventions improved the level of acceptance, participation and positive health outcomes within the faith communities., Conclusion: Religious leaders and faith organisations have the potential to influence health education, health promotion and positive health outcomes amongst members of their faith community. They also provide potential access to at-risk populations for increasing awareness about SCD, encouraging health service utilization and ethnic blood donor drives.