•Omega−3 fatty acids have effects on diverse physiological processes.•Omega−3 fatty acids have anti-inflammatory properties.•Sickle cell disease blood cell membranes have low omega-3 fatty acid ...composition.•Docosahexaenoic acid (DHA) treatment restores sickle membrane fatty acid balance.•DHA therapy in SCD reduces vaso-occlusion, inflammation, adhesion and hemolysis.
Sickle cell disease (SCD) is a hematologic disorder with complex pathophysiology that includes chronic hemolysis, vaso-occlusion and inflammation. Increased leukocyte-erythrocyte-endothelial interactions, due to upregulated expression of adhesion molecules and activated endothelium, are thought to play a primary role in initiation and progression of SCD vaso-occlusive crisis and end-organ damage. Several new pathophysiology-based therapeutic options for SCD are being developed, chiefly targeting the inflammatory pathways.
Omega−3 fatty acids are polyunsaturated fatty acids that are known to have effects on diverse physiological processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the principal biologically active omega-3 fatty acids. The therapeutic effects of DHA and EPA on chronic inflammatory disorders and cardiovascular diseases are well recognized. The therapeutic effects of omega-3 fatty acids are attributed to their anti-inflammatory and anti-thrombotic eicosanoids, and the novel class of EPA and DHA derived lipid mediators: resolvins, protectins and maresins.
Blood cell membranes of patients with SCD have abnormal fatty acids composition characterized by high ratio of pro-inflammatory arachidonic acid (AA) to anti-inflammatory DHA and EPA (high omega-6/omega-3 ratio). In addition, experimental and clinical studies provide evidence that treatment with DHA does confer improvement in rheological properties of sickle RBC, inflammation and hemolysis. The clinical studies have shown improvements in VOC rate, markers of inflammation, adhesion, and hemolysis. In toto, the results of studies on the therapeutic effects of omega-3 fatty acids in SCD provide good body of evidence that omega-3 fatty acids could be a safe and effective treatment for SCD.
Blood cell aggregation and adherence to vascular endothelium and inflammation play a central role in vaso-occlusive crisis in sickle cell disease. The antiaggregatory, antiadhesive, antiinflammatory, ...and vasodilatory omega-3 (n-3) fatty acids (DHA and EPA) are significantly reduced in patients with the disease.
The aim was to investigate the therapeutic potential of omega-3 fatty acids for patients with homozygous sickle cell disease in a randomized, placebo-controlled, double-blind trial.
One hundred forty patients recruited from a single center in Sudan were randomly assigned and received, daily, 1 (age 2-4 y), 2 (age 5-10 y), 3 (age 11-16 y), or 4 (age ≥17 y) omega-3 capsules containing 277.8 mg DHA and 39.0 mg EPA or placebo for 1 y. Of these patients, 128 were followed up and the data were obtained. The primary and secondary endpoints-rates of clinical vaso-occlusive crisis and hemolytic events, blood transfusion rate, school attendance, and blood count-were analyzed by intention-to-treat analysis (n = 140).
Omega-3 treatment reduced the median rate of clinical vaso-occlusive events (0 compared with 1.0 per year, P < 0.0001), severe anemia (3.2% compared with 16.4%; P < 0.05), blood transfusion (4.5% compared with 16.4%; P < 0.05), white blood cell count (14.4 ± 3.3 compared with 15.6 ± 4.0 ×10(3)/μL; P < 0.05), and the OR of the inability to attend school at least once during the study period because of illness related to the disease to 0.4 (95% CI: 0.2, 0.9; P < 0.05).
The findings of this trial, which need to be verified in a large multicenter study, suggest that omega-3 fatty acids can be an effective, safe, and affordable therapy for sickle cell anemia. This trial was registered with Current Controlled Trials as ISRCTN80844630.
Chronic inflammation and reduced blood levels of omega-3 fatty acids (n−3) are known characteristics of sickle cell disease (SCD).The anti-inflammatory properties of n−3 fatty acids are well ...recognized.
Omega-3 treated (n=24), hydroxyurea (HU) treated (n=18), and n−3 untreated (n=21) homozygous SCD patients (HbSS) and healthy (HbAA) controls (n=25) matched for age (5–16years), gender and socioeconomic status were studied. According to age (5–10) or (11–16) years, two or three capsules containing 277.8mg docosahexaenoic (DHA) and 39.0mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned to n−3 treated and n−3 untreated groups, respectively. Hydroxyurea treated group was on dosage more than 20mg/kg/day. The effect of supplementation on systemic and blood cell markers of inflammation was investigated.
The n−3 treated group had higher levels of DHA and EPA (p<0.001) and lower white blood cell count and monocyte integrin (p<0.05) compared with the n−3 untreated. No difference was detected between the two groups regarding C-reactive protein, granulocytes integrin and selectin, plasma tumour necrosis factor-α and interleukin-10. The n−3 treated group had lowered nuclear factor-kappa B (NF-κB) gene expression compared to n−3 untreated and HU treated groups (p<0.05).
This study provides evidence that supplementation with n−3 fatty acids may ameliorate inflammation and blood cell adhesion in patients with SCD.
Summary
Objective
To investigate the epidemiology of sickle cell disease (SCD) and determinants of knowledge, attitudes and practices (KAP) towards SCD in western Kordofan State, Sudan.
Methods
A ...community‐based, descriptive, cross‐sectional study was conducted in three towns. Three hundred and seventy‐two households were polled, and blood samples for haemoglobin phenotyping were collected from 1116 individuals. Sociodemographic, socio‐economic and KAP data were collected using investigator‐administered questionnaires. Descriptive, frequency distribution and multiple regression analyses were performed.
Results
About 50.9% of the study population were Misseriya tribes. Consanguineous marriages were reported by 67.5% of the households. The highest percentage of homozygous SCD was 2.8% among children under 5 years of age. About 24.9% were carriers of HbS allele (HbAS). HbS allele frequency was highest in children aged 5–11 years (18.3%, CI: 13.7–22.9%) and lowest in males >15 years old (12.0%, CI: 6.1–17.9%). The average HbS frequency across all age groups was 14.5% (95% CI: 12.2–16.8%). The most frequent β‐globin gene cluster haplotype was the Cameroon (30.8%), followed by the Benin (21.8%), the Senegal (12.8%) and the Bantu (2.2%) haplotypes. About 17.0% of all‐cause child deaths were due to SCD. The estimated change in log odds of having the SS genotype per year increase in age was (−) 0.0058 (95% CI −0.0359, 0.0242). This represents a non‐statistically significant 2.9% increase in 5‐year mortality for individuals with the SS genotype relative to those with AS and AA genotypes. About 46.9% of the households had poor knowledge, 26.1% had satisfactory knowledge, and 26.9% had good knowledge about sickle cell disease. Mothers' and fathers' educational levels were significant predictors of good knowledge about SCD (P < 0.05). About 48.0% had a satisfactory attitude towards sickle cell disease while 30.7% had poor attitude and only 21.3 showed good attitudes. Poor knowledge about SCD and low socio‐economic status were the strongest positive predictors of poor attitude and practices towards SCD (P < 0.01).
Conclusions
Sickle cell disease is a major health problem in West Kordofan, Sudan. Knowledge, attitude and practices towards the disease are not satisfactory. The development of public health programs is highly recommended to control and manage SCD in western parts of Sudan.
Objectif
Etudier l’épidémiologie de la drépanocytose et les déterminants des connaissances, attitudes et pratiques (CAP) vis‐à‐vis de la maladie dans l'Etat du Kordofan Occidental, au Soudan.
Méthodes
Etude communautaire descriptive, transversale, dans trois villes. 372 ménages ont été investigués et des échantillons de sang pour le phénotypage de l'hémoglobine ont été recueillis chez 1116 individus. Les données sociodémographiques, socioéconomiques et CAP ont été recueillies au moyen de questionnaires administrés par les enquêteurs. Des analyses descriptives, sur les fréquences de distribution et de régression multiple ont été effectuées.
Résultats
Les personnes de la tribu Messiria constituaient 50,9% de la population étudiée. Des mariages consanguins ont été rapportés par 67,5% des ménages. Le pourcentage le plus élevé des homozygotes de la drépanocytose était de 2,8% chez les enfants de moins de 5 ans. 24,9% étaient porteurs de l'allèle HbS (HbAS). La fréquence des allèles HbS était la plus élevée chez les enfants de 5 à 11 ans (18,3%, IC: 13,7% ‐22,9%) et la plus faible chez les hommes > 15 ans (12,0%, IC: 6,1% ‐17,9%). La fréquence moyenne de l'HbS pour tous les groupes d’âge était de 14,5% (IC95%: 12,2% ‐16,8%). Les regroupements des haplotypes du gène de la β‐globine les plus fréquents étaient ceux du Cameroun (30,8%), suivie par ceux du Bénin (21,8%), du Sénégal (12,8%) et des Bantous (2,2%). 17,0% de tous les causes de décès d'enfants étaient dus à la drépanocytose. La variation estimée du logarithme des chances d'avoir le génotype SS par année d'augmentation de l’âge était de (‐) 0,0058 (IC95% : ‐0,0359 à 0,0242). Ce qui représente une augmentation non statistiquement significative de 2,9% de la mortalité des moins de cinq ans pour les individus ayant le génotype SS par rapport à ceux avec les génotypes AS et AA. 46,9% des ménages avaient de mauvaises connaissances, 26,1% avaient des connaissances satisfaisantes et 26,9% avaient de bonnes connaissances sur la drépanocytose. Les niveaux d’éducation des mères et des pères étaient des facteurs prédictifs significatifs de bonnes connaissances sur la drépanocytose (p <0,05). 48,0% avaient des attitudes satisfaisantes vis‐à‐vis de la drépanocytose tandis que 30,7% avaient de mauvaises attitudes et seulement 21,3% ont montré de bonnes attitudes. De mauvaises connaissances sur la drépanocytose et le faible statut socioéconomique étaient les facteurs prédictifs positifs les plus forts des mauvaises attitudes et pratiques vis‐à‐vis de la drépanocytose (p <0,01).
Conclusions
La drépanocytose est un problème de santé majeur dans le Kordofan occidental, au Soudan. Les connaissances, attitudes et pratiques à l’égard de la maladie ne sont pas satisfaisants. Le développement de programmes de santé publique est fortement recommandé pour contrôler et prendre en charge la drépanocytose dans les régions occidentales du Soudan.
Objetivo
Investigar la epidemiología de la anemia falciforme (AF) y los determinantes de conocimientos, actitudes y prácticas (CAP) frente a la AF en el Estado de Kordofan del Oeste en Sudán.
Métodos
Estudio basado en la comunidad, descriptivo y crosseccional en tres poblados. Se encuestaron 372 hogares y se tomaron muestras de sangre a 1116 individuos para fenotipar la hemoglobina. Se recolectaron datos socio‐demográficos, socio‐económicos y de CAP utilizando cuestionarios administrados por los investigadores. Se realizaron análisis descriptivos, de distribución de frecuencias y de regresión múltiple.
Resultados
La tribu Messiria constituía un 50.9% de la población de estudio. Se reportaron matrimonios consanguíneos en 67.5% de los hogares. El más alto porcentaje de AF homocigota era del 2.8% en niños menores de 5 años de edad. 24.9% eran portadores del alelo HbS (HbAS). La frecuencia del alelo HbS era mayor en niños con edades entre los 5‐11 años (18.3%, IC: 13.7%‐22.9%) y menor en hombres >15 años (12.0%, IC: 6.1%‐17.9%). El promedio de frecuencia de HbS en todos los grupos de edad era del 14.5% (IC 95%: 12.2%‐16.8%). El haplotipo más frecuente del gen de la globina beta era el de Camerún (30.8%), seguido por los haplotipos Benín (21.8%) y Senegal (12.8%) y el Bantú (2.2%). Un 17.0% de la mortalidad por cualquier causa en niños era debida a la AF. El cambio estimado en la probabilidad de tener el genotipo SS por año incrementado en edad era (‐) 0.0058 (IC95% ‐0.0359, 0.0242). Esto representa un aumento estadísticamente no significativo del 2.9% en la mortalidad a cinco años para individuos con el genotipo SS en comparación con aquellos con los genotipos AS y AA. Un 46.9% de los hogares tenía un conocimiento pobre, un 26.1% tenía un conocimiento satisfactorio y un 26.9% tenía un buen conocimiento sobre la AF. Los niveles de educación de las madres y padres eran vaticinadores significativos de buen conocimiento sobre la AF (p<0.05). Un 48.0% tenía una actitud satisfactoria sobre AF mientras que un 30.7% tenía una actitud pobre y solo un 21.3% tenía una buena actitud. Un conocimiento pobre sobre la AF y un estatus socioeconómico bajo eran los principales vaticinadores positivos de una actitud y prácticas pobres frente a la AF (p<0.01).
Conclusiones
La AF es un problema de salud mayor en Kordofan del Oeste, Sudán. Los conocimientos, actitud y prácticas frente a la enfermedad no son satisfactorios. Es altamente recomendable desarrollar programas de salud pública para el control y el manejo de la AF en áreas occidentales de Sudán.
The omega-3 (n−3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence ...that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with drug-resistant epilepsy (DRE) was investigated.
A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (n = 99) subjects with DRE, aged 5–16 years (n = 85) and 17–45 years (n = 14). After randomization, subjects were given two, four, or six capsules per day of DHA (417.8 mg DHA and 50.8 mg EPA/capsule, n = 33), EPA (385.6 mg EPA and 81.2 mg DHA/capsule, n = 33), or placebo (high oleic acid sunflower oil, n = 33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients' total count of seizures per month. The treatment effects on seizure incidence rate ratio (IRR) were tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure, and number of antiepileptic drug (AED) combinations used at enrollment.
Fifty-nine subjects (n = 59) completed the study (59.6%). The average number of seizures per month were 9.7 ± 1.2 in the EPA group, 11.7 ± 1.5 in the DHA group, and 16.6 ± 1.5 in the placebo group. Age, gender, and seizure-type adjusted seizure IRRs of the EPA and DHA groups compared with the placebo group were 0.61 (CI = 0.42–0.88, p = 0.008, 42% reduction) and 0.67 (CI = 0.46–1.0, p = 0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (p = 0.56). Both treatment groups had a significantly higher number of seizure-free days compared with the placebo group (p < 0.05).
This study demonstrates that EPA and DHA are effective in reducing seizure frequency in patients with DRE.
•Eicosapentaenoic acid (EPA) and docosahexaenoic acid (EPA), are known to modify neuronal function and excitability.•Treatment with DHA or EPA reduces seizure rate in patients with Drug Resistant Epilepsy (DRE) by 39% and 42% respectively.•DHA and EPA reduces the number of seizure-free days. DHA and EPA had a comparable therapeutic effects in patients with DRE.
The epidemiology of viral hepatitis during pregnancy is essential for health planners and programme managers. While much data exist concerning viral hepatitis during pregnancy in many African ...countries, no proper published data are available in Sudan.
The study aimed to investigate the sero-prevalence and the possible risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) among antenatal care attendants in central Sudan.
During 3 months from March-June 2006, sera were collected from pregnant women at Umdurman Maternity Hospital in Sudan, and they were tested for markers of hepatitis B virus (HBVsAg) and HCV.
HBVsAg was detected in 41 (5.6%) out 728 women, Anti-HCV was detected in 3 (0.6%) out of 423 women, all of them were not aware of their condition. Age, parity, gestational age, residence, history of blood transfusion, dental manipulations, tattooing and circumcision did not contribute significantly to increased HBVsAg sero-positivity.
Thus 5.6% of pregnant women were positive for HBVsAg irrespective of their age, parity and socio-demographic characteristics. There was low prevalence of Anti-HCV.
Abstract We investigated whether or not Omega-3 long-chain polyunsaturated fatty acid (omega-3 LCPUFA) supplementation exacerbates oxidative stress in homozygous sickle cell patients aged 2 to 14 ...years. Depending on their age, they received between one and three omega-3 (277.8 mg DHA and 39.0 mg EPA/capsule) or placebo (high oleic acid sunflower seed oil) capsules for one year. Supplementation increased significantly the levels of the two fatty acids in red cell phosphatidylcholine and phosphatidylethanolamine ( p <0.001). The patients who received omega-3 LCPUFA compared with their placebo-taking counterparts had a higher concentration of plasma vitamin E at one year (14.3±2.8 versus 12.3±2.8 µmol/l; p <0.001). The two groups had comparable concentrations of the vitamin at six month intervention (10.8±2.2 versus 10.7±2.9 µmol/l; p >0.05) and baseline (10.7±3.1 versus 10.7±2.8 µmol/l; p >0.05). After six month of intervention, the patients on omega 3 fatty acids had lower GPx-1 (33.5±13.4 versus 46.6 ±17.6, p <0.01) and Cu/Zn-SOD (1070±600 versus 1470±690 p <0.05) activities than at baseline. GPx-1 (33.5±17.6 IU/g Hb versus 43.7±13.2 IU/g Hb; p <0.01) and Cu/Zn-SOD (1070±600 IU/g Hb versus 1360±920 IU/g Hb; p >0.05) activities were reduced in the omega 3 compared with the placebo at six month intervention. There was no difference in the activity of either of the enzymes between baseline and six month intervention in the placebo group ( p >0.05). This study demonstrates; DHA and EPA supplementation, rather than exacerbating the inherent oxidative stress associated with the disease, seems to provide an antioxidant protection. Hence, it will be safe to provide omega-3 LCPUFA to sickle cell patients to help ameliorate vaso-occlusive and haemolytic crises and membrane fatty acid abnormality.
Sickle cell disease (SCD) is one of the most common inherited blood disorder among African Americans affecting 70,000–100,000 individuals in the United States. It is characterized by abnormal ...hemoglobin (HbS) which develops into severe hemolytic anemia and vaso-occlusive crisis. Therefore, patients with SCD suffer from a chronic state of inflammation, which is responsible for multiple organ damage, ischemic attacks, and premature death. Another major hallmark of SCD patients is the abnormally low levels of omega-3 fatty acids, especially docosahexaenoic acid (DHA) in their red blood cell membranes. Treatment with DHA can reduce red blood cell adhesion and enhance cerebral blood flow, thus, our main goal is to investigate the effect of SC411, which is a novel, highly purified DHA ethyl ester formulation with a proprietary delivery platform in SCD. Utilizing a transgenic mouse model of SCD (HbSS-Townes) and recurrent hypoxic challenges (10%O2, 0.5% CO2 and balance N2 for 3 h) to mimic ischemic-like conditions, our data suggest that SC411 can elevate blood DHA and eicosapentaenoic acid (EPA) levels after 8 weeks of treatment. SC411 can also decrease arachidonic acid (AA) and sickling of red blood cells. In addition, SC411-treated SCD mice showed presented with cerebral blood flow, alleviated neuroinflammation, and revived working memory which ultimately enhanced overall survival. In summary, this study suggests that treatment with SC411 improves cellular and functional outcomes in SCD mice. This finding may provide novel therapeutic opportunities in the treatment against ischemic injury elicited by SCD.
Background:
Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk ...of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 109/L and increase from baseline ⩾20 × 109/L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels.
Objectives:
Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP.
Design:
Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study.
Methods and analysis:
The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 109/L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy.
Ethics:
Ethical guidelines and informed consent are followed.
Discussion:
The LUNA 3 trial will further investigate rilzabrutinib’s safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response.
Trail Registration:
ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60.
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