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PloS One 2024Sickle cell disease (SCD) remains a public health problem especially in sub-Saharan Africa including Ghana. While pilot initiatives in Africa have demonstrated that...
Barriers and facilitators to community acceptability of integrating point-of-care testing to screen for sickle cell disease in children in primary healthcare settings in rural Upper East Region of Northern Ghana.
INTRODUCTION
Sickle cell disease (SCD) remains a public health problem especially in sub-Saharan Africa including Ghana. While pilot initiatives in Africa have demonstrated that neonatal screening coupled with early intervention reduces SCD-related morbidity and mortality, only 50-70% of screen-positive babies have been successfully retrieved to benefit from these interventions. Point-of-care testing (POCT) with high specificity and sensitivity for SCD screening can be integrated into existing immunization programs in Africa to improve retrieval rates. This study explored community acceptability of integrating POCT to screen for SCD in children under 5 years of age in primary healthcare facilities in Northern Ghana.
METHOD
This was an exploratory study using qualitative research approach where 10 focus group discussions and 20 in-depth interviews were conducted with community members and health workers between April and June 2022. The recorded interviews were transcribed verbatim after repeatedly listening to the recordings. Data was coded into themes using QSR Nvivo 12 software before thematic analysis.
RESULTS
Most participants (70.9%) described SCD as serious and potentially life-threatening condition affecting children in the area. Of 148 community members and health workers, 141 (95.2%) said the screening exercise could facilitate diagnosis of SCD in children for early management. However, discrimination, fear of being tested positive, stigmatization, negative health worker attitude linked with issues of maintaining confidentiality were reported by participants as key factors that could affect uptake of the SCD screening exercise. Most participants suggested that intensive health education (78.3%), positive attitude of health workers (69.5%), and screening health workers not being biased (58.8%) could promote community acceptability.
CONCLUSION
A large majority of participants viewed screening of SCD in children as very important. However, opinions expressed by most participants suggest that health education and professionalism of health workers in keeping patients' information confidential could improve the uptake of the exercise.
Topics: Humans; Anemia, Sickle Cell; Ghana; Primary Health Care; Female; Male; Point-of-Care Testing; Child, Preschool; Adult; Rural Population; Infant; Patient Acceptance of Health Care; Health Personnel; Mass Screening; Middle Aged; Infant, Newborn; Young Adult; Focus Groups
PubMed: 38768171
DOI: 10.1371/journal.pone.0303520 -
BioRxiv : the Preprint Server For... May 2024Alpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated...
Alpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated α-globin genes, and disease severity is directly related to the number of allelic copies compromised. The most severe form, α-thalassemia major (αTM), results from loss of all four copies of α-globin and has historically resulted in fatality . However, transfusions now enable survival to birth. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to imbalance of β-globin and α-globin chains. While curative, hematopoietic stem cell transplantation (HSCT) is limited by donor availability and potential transplant-related complications. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for patients suffering from α-thalassemia. To address this, we designed a novel Cas9/AAV6-mediated genome editing strategy that integrates a functional α-globin gene into the β-globin locus in αTM patient-derived hematopoietic stem and progenitor cells (HSPCs). Incorporation of a truncated erythropoietin receptor transgene into the α-globin integration cassette dramatically increased erythropoietic output from edited HSPCs and led to the most robust production of α-globin, and consequently normal hemoglobin. By directing edited HSPCs toward increased production of clinically relevant RBCs instead of other divergent cell types, this approach has the potential to mitigate the limitations of traditional HSCT for the hemoglobinopathies, including low genome editing and low engraftment rates. These findings support development of a definitive autologous genome editing strategy that may be curative for α-thalassemia.
PubMed: 38766216
DOI: 10.1101/2023.09.01.555926 -
Medicine May 2024Sickle Cell Anemia (SCA) is a hereditary hemoglobinopathy characterized by chronic hemolytic anemia, vaso-occlusive events, and a wide range of clinical complications.... (Review)
Review
Sickle Cell Anemia (SCA) is a hereditary hemoglobinopathy characterized by chronic hemolytic anemia, vaso-occlusive events, and a wide range of clinical complications. Malnutrition, often an underexplored aspect of this complex condition, plays a critical role in disease management and overall patient well-being. This publication provides a comprehensive review of the prevalence, impact, and interventions related to malnutrition in individuals with SCA. A thorough literature review reveals the multifaceted challenges faced by SCA patients in maintaining adequate nutrition. The pathophysiology of SCA, involving chronic inflammation, oxidative stress, and hypermetabolism, contributes to increased nutritional requirements and altered dietary patterns. Factors such as reduced appetite, nutrient malabsorption, dietary restrictions, and socioeconomic disparities further exacerbate the risk of malnutrition. Malnutrition is a prevalent issue among individuals with SCA, affecting patients of different age groups and disease severities. Nutritional deficiencies, including vitamins, minerals, and essential nutrients, are common in this population. The impact of malnutrition on disease outcomes is significant, with associations between nutrient status and complications such as pain crises, infections, and impaired quality of life. This paper also reviews nutritional interventions aimed at addressing malnutrition in SCA patients. While dietary counseling, supplementation, and personalized nutrition plans have shown promise in improving nutritional status, challenges such as patient adherence and access to healthcare must be addressed to optimize their effectiveness.
Topics: Humans; Anemia, Sickle Cell; Malnutrition; Prevalence; Quality of Life; Nutritional Status
PubMed: 38758879
DOI: 10.1097/MD.0000000000038164 -
Medicine May 2024Mild to moderate thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) and they exhibit highly...
BACKGROUND
Mild to moderate thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) and they exhibit highly similar clinical and laboratory features. It is sometimes difficult to make a differential diagnosis between TT and IDA in clinical practice. Therefore, a simple, effective, and reliable index is needed to discriminate between TT and IDA.
METHODS
Data of 598 patients (320 for TT and 278 for IDA) were enrolled and randomly assigned to training set (278 of 598, 70%) and validation set (320 of 598, 30%). Stepwise discriminant analysis was used to define the best diagnostic formula for the discrimination between TT and IDA in training set. The accuracy and diagnostic performance of formula was tested and verified by receiver operating characteristic (ROC) analysis in validation set and its diagnostic performance was compared with other published indices.
RESULTS
A novel formula, Thalassemia and IDA Discrimination Index (TIDI) = -13.932 + 0.434 × RBC + 0.033 × Hb + 0.025 ×MCHC + 53.593 × RET%, was developed to discriminate TT from IDA. TIDI showed a high discrimination performance in ROC analysis, with the Area Under the Curve (AUC) = 0.936, Youden' s index = 78.7%, sensitivity = 89.5%, specificity = 89.2%, respectively. Furthermore, the formula index also obtained a good classification performance in distinguishing 5 common genotypes of TT from IDA (AUC from 0.854-0.987).
CONCLUSION
The new, simple algorithm can be used as an effective and robust tool for the differential diagnosis of mild to moderate TT and IDA in Guangxi region, China.
Topics: Humans; Anemia, Iron-Deficiency; Diagnosis, Differential; Male; Female; Thalassemia; Adult; Algorithms; Discriminant Analysis; ROC Curve; Adolescent; Young Adult; Middle Aged; Sensitivity and Specificity
PubMed: 38758841
DOI: 10.1097/MD.0000000000038205 -
Indian Journal of Medical Ethics 2024Saviour babies or saviour siblings are conceived specifically to be sources of biological materials - ranging from cord blood, stem cells or even organs - to save...
Saviour babies or saviour siblings are conceived specifically to be sources of biological materials - ranging from cord blood, stem cells or even organs - to save another child, usually an older sibling, who is suffering from a disease like thalassemia that can be cured with this biological material. In 2020, the media reported about the birth of India's first saviour baby, in the state of Gujarat [1]. In January 2023, there was a report of the birth of another saviour baby, in the state of Maharashtra [2]. Ethical concerns relating to saviour siblings find a place in the western bioethics discourse. However, it is little discussed in the Indian context.
Topics: Humans; India; Siblings; Female; Thalassemia
PubMed: 38755767
DOI: 10.20529/IJME.2024.012 -
Lipids in Health and Disease May 2024Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A...
Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A serious complication of SCD is acute chest syndrome (ACS). ACS is a condition with a high rate of morbidity and mortality. The aim of the study was to assess hemolysis and lipid parameters in a cohort of confirmed SCD patients to predict ACS development in the following year.Standard lipid were performed (triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol) panel to calculate of non-HDL-C, large buoyant LDL cholesterol (lbLDL-C) and small dense LDL cholesterol (sdLDL-C) with Sampson equation. Hemolysis and hematologic parameters were also evaluated.Among 91 patients included between September 2018 and June 2021, thirty-seven patients had history of ACS and 6 patients developed ACS during following year. In unadjusted logistic regression, total bilirubin was associated with ACS occurrence (RR: 1.2 [1.05-1.51] p = 0.013). Concerning lipid profile, non-HDL-C (RR: 0.87 [0.0.67-0.99] p = 0.04) and sdLDL-C (RR: 0.78 [0.49-0.96] p = 0.03) were associated with ACS occurrence decrease. C-reactive protein was associated with ACS occurrence (RR: 1.27 [1.065-1.85] p = 0.011).Based on these findings, this study demonstrated that several biomarker easily available can be used at steady state to predict ACS in the following year. The validation of these results are required to ensure the reproducibility of the findings.
Topics: Humans; Anemia, Sickle Cell; Male; Female; Acute Chest Syndrome; Adult; Hemolysis; Cholesterol, LDL; Middle Aged; Triglycerides; Cholesterol, HDL; Bilirubin; Lipids
PubMed: 38755670
DOI: 10.1186/s12944-024-02135-8 -
PloS One 2024Despite the huge burden of sickle cell disease (SCD) among Nigerian children, the burden and outcome of respiratory illnesses remain undocumented. Thus, we aimed to...
Burden and outcome of respiratory morbidities among children and adolescents with sickle cell disease-A retrospective review of emergency presentations in some Nigerian tertiary institutions.
BACKGROUND
Despite the huge burden of sickle cell disease (SCD) among Nigerian children, the burden and outcome of respiratory illnesses remain undocumented. Thus, we aimed to describe the spectrum and outcome of respiratory illnesses among SCD childrenand adolescentadmissions in ten Nigerian tertiary hospitals.
METHOD
A retrospective review of the SCD admission records of children and adolescents with a confirmed diagnosis of respiratory illnesses from 2012 to 2021 in ten tertiary health facilities across five geopolitical zones in Nigeria was conducted. The data, collectedbetween March and June 2023, included the age, sex, diagnosis, complications, duration and outcome of hospitalization.
RESULTS
Of the 72,333 paediatric admissions, 7,256 (10.0%) had SCD; the proportion of SCD from the total admission ranged from 2.1 to 16.3% in the facilities. Of the 7,256 children and adolescents with SCD, 1,213 (16.7%) had respiratory morbidities. Lower respiratory disease was the most common (70.0%) respiratory entity and the majority were pneumonia (40.1.0%), followed by acute chest syndrome (26.7%). Seventeen (1.4%) patients died; all had lower respiratory diseases [(acute chest syndrome ACS (11, 64.7%), pneumonia; 5, 29.4%, and asthma (1, 5.9%). Based on the proportion of deaths among overall SCD, the 17 death cases contributed 9.4% (95% CI 5.9 to 14.5). Factors associated with deaths included duration of hospitalization less than 72 hours and lower respiratory tract diseases.
CONCLUSION
Sickle cell disease is a major contributor to hospitalization among Nigerian children and adolescents, with high respiratory morbidity and mortality. Pneumonia and acute chest syndrome were associated with mortality, andthe highest risk of death within the first 72 hours.
Topics: Humans; Anemia, Sickle Cell; Adolescent; Child; Nigeria; Male; Female; Retrospective Studies; Tertiary Care Centers; Child, Preschool; Infant; Hospitalization; Respiratory Tract Diseases; Acute Chest Syndrome; Cost of Illness
PubMed: 38753737
DOI: 10.1371/journal.pone.0303323 -
HemaSphere May 2024α-Thalassemia represents one of the most important genetic modulators of β-hemoglobinopathies. During this last decade, the ongoing interest in characterizing...
α-Thalassemia represents one of the most important genetic modulators of β-hemoglobinopathies. During this last decade, the ongoing interest in characterizing genotype-phenotype relationships has yielded incredible insights into α-globin gene regulation and its impact on β-hemoglobinopathies. In this review, we provide a holistic update on α-globin gene expression stemming from DNA to RNA to protein, as well as epigenetic mechanisms that can impact gene expression and potentially influence phenotypic outcomes. Here, we highlight defined α-globin targeted strategies and rationalize the use of distinct molecular targets based on the restoration of balanced α/β-like globin chain synthesis. Considering the therapies that either increase β-globin synthesis or reactivate γ-globin gene expression, the modulation of α-globin chains as a disease modifier for β-hemoglobinopathies still remains largely uncharted in clinical studies.
PubMed: 38752170
DOI: 10.1002/hem3.78 -
Scientific Reports May 2024This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and...
This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and metabolic variables during exercise. Knowing that diastolic dysfunction is frequent in this population, we hypothesize that a lack of cardiac adaptation through exercise might lead to premature increase in blood lactate concentrations in SCA patients, a potential trigger for acute disease complication. SCA patients were prospectively included in PHYSIO-EXDRE study and underwent a comprehensive stress test with a standardized incremental exercise protocol up to 4 mmol L blood lactate concentration (BL4). Gas exchange, capillary lactate concentration and echocardiography were performed at baseline, during stress test (at ∼ 2 mmol L) and BL4. The population was divided into two groups and compared according to the median value of percentage of theoretical peak oxygen uptake (% ) at BL4. Twenty-nine patients were included (42 ± 12 years old, 48% of women). Most patients reached BL4 at low-intensity exercise [median value of predicted power output (W) was 37%], which corresponds to daily life activities. The median value of % at BL4 was 39%. Interestingly, diastolic maladaptation using echocardiography during stress test along with hemoglobin concentration were independently associated to early occurrence of BL4. As BL4 occurs for low-intensity exercises, SCA patients may be subject to acidosis-related complications even during their daily life activities. Beyond assessing physical capacities, our study underlines that diastolic maladaptation during exercise is associated with an early increase in blood lactate concentration.
Topics: Humans; Anemia, Sickle Cell; Male; Female; Adult; Diastole; Middle Aged; Exercise Tolerance; Exercise Test; Pilot Projects; Echocardiography; Adaptation, Physiological; Lactic Acid; Prospective Studies; Oxygen Consumption; Exercise
PubMed: 38750085
DOI: 10.1038/s41598-024-61689-w -
Revista Da Associacao Medica Brasileira... 2024The ability to cause death is the definitive measure of an infectious disease severity, particularly one caused by a novel pathogen like severe acute respiratory...
OBJECTIVE
The ability to cause death is the definitive measure of an infectious disease severity, particularly one caused by a novel pathogen like severe acute respiratory syndrome-CoV-2 (COVID-19). This study describes sickle cell disease-related mortality issues during the COVID-19 pandemic in Brazil.
METHODS
The provisional 2020 mortality data originated from the public databases of the Mortality Information System and were investigated using the multiple-cause-of-death methodology.
RESULTS
In 2020, 688 sickle cell disease-related deaths occurred, of which 422 (61.3%) had an underlying cause of death and 266 (38.7%) had an associated cause of death. Furthermore, 98 COVID-19-related deaths occurred, of which 78 were underlying cause of death among sickle cell disease associated (non-underlying) cause of death. Sickle cell disease-related deaths occurred mostly among young adults aged 25-49 years. COVID-19 deaths occurred at ages older than among sickle cell disease-related deaths. Majority of deaths happened in the southeast (42.3%) and northeast regions (34.0%), while COVID-19 deaths prevailed in the northeast region (42.9%). Regarding overall deaths, the leading underlying cause of death was sickle cell disease itself, followed by infectious and parasitic diseases (14.8%), owing to COVID-19 deaths, and diseases of the circulatory system (8.9%). Next, in males, diseases of the digestive system (4.8%) occurred, while, in females, maternal deaths succeeded, included in the chapter on pregnancy, childbirth, and the puerperium, accounting for 5.9% of female deaths. The leading overall associated (non-underlying) cause of deaths were septicemias (29.4%), followed by respiratory failure (20.9%), pneumonias (18.3%), and renal failure (14.7%).
CONCLUSION
In Brazil, COVID-19 deaths produced trend changes in sickle cell disease-related causes of death, age at death, and regional distribution of deaths in 2020.
Topics: Humans; COVID-19; Anemia, Sickle Cell; Brazil; Adult; Female; Middle Aged; Male; Cause of Death; Young Adult; SARS-CoV-2; Adolescent; Child; Pandemics; Aged; Child, Preschool; Age Distribution
PubMed: 38747879
DOI: 10.1590/1806-9282.20231466