Mohamed Badr

Deviating from safety guidelines during deferiprone therapy in clinical practice may not be associated with higher risk of agranulocytosis

A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC) <1.5u2009×u2009109/L, out of concern that continued therapy might lead to a more severe drop. However, it is uncertain how these recommendations are followed under real‐life conditions and, if they are not followed, whether continuation of therapy results in increased incidence of agranulocytosis.

Renal tubular dysfunction in children with sickle cell haemoglobinopathy

Children with sickle cell disease (SCD) are remarkably more prone than others to renal dysfunction. The kidneys, as one of the systemic long‐term hazards in SCD, may be affected by both the haemodynamic changes of chronic anaemia as well as by the consequences of vaso‐occlusion. The aim of this study was to evaluate the proximal tubular function in a group of Saudi children with established SCD.

Successful utilization of an electronic pain diary in a multinational phase 3 interventional study of pediatric sickle cell anemia

Background/Aims: Patients with sickle cell anemia can experience recurrent pain episodes, which affect quality of life. The reported prevalence of pain is higher in studies using patient diaries than in healthcare facility utilization data. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events was a multinational study that assessed the efficacy and safety of prasugrel in reducing the rate of vaso-occlusive events in children with sickle cell anemia (NCT01794000) and included an electronic patient-reported outcome diary to record pain occurrence. We aimed to capture diary completion rates and compliance in children who used the electronic patient-reported outcome diary during the Determining Effects of Platelet Inhibition on Vaso-Occlusive Events study and examine factors contributing to diary completion rates and compliance. Methods: Daily electronic patient-reported outcome diary data were collected for up to 9u2009months in Determining Effects of Platelet Inhibition on Vaso-Occlusive Events participants aged 4 to <18u2009years in Africa, the Americas, Europe, and the Middle East. The questionnaires were available in 11 languages/dialects for collecting subjective (pain intensity, activity interference) and objective (study drug use, analgesic use, school attendance) data. Pain intensity was measured using the Faces Pain Scale–Revised. Data were entered by participants or caregivers and transferred wirelessly each day to a central database. Diary completion rates were the number of daily diary entries divided by the total number of expected daily diary entries. Percentages of participants who were compliant with the diary (≥80% diary completion) were calculated. Results: A total of 311 participants received a diary; 268 provided diary data through Month 9. Diary completion rates and compliance were high throughout the collection period and across all groups and regions, despite no games being included on the device. For subjective data, the overall completion rate was 94.4%, and 92.6% of participants were compliant. For objective data, the overall completion rate was 93.3%, and 89.7% of participants were compliant. Completion rates and compliance differed significantly by age and region and were higher for 4 to <12u2009year olds and very much higher for participants from Africa and the Middle East. Caregivers almost always entered data for participants <6u2009years and rarely entered data for participants ≥12u2009years. Comparing participant-entered and caregiver-entered data, pain intensity score data were more consistent for 4 to <12u2009year olds than older children, but pain intensity scores for older children were higher when entered by caregivers. Conclusion: With appropriate design, participant training, and sufficient monitoring, an electronic patient-reported outcome diary can capture daily sickle cell–related pain data in large multinational studies. Providing a mechanism for caregiver reporting is particularly valuable for participants <6u2009years and may also facilitate compliance in older children who experience high levels of pain.

Comparative biochemical studies on steroidogenic compounds in chickens.

Comparative studies of the effects of Nordette and Lutofolone on 15 days old chicken were carried out to determine their effects on growth performance, biochemical parameters and an analysis of hormonal residues in the liver and muscle. Sixty chickens were equally divided into three groups. Group 1 was served as a control. Groups 2 and 3 were treated daily with Nordette (1 mg/kg B.W.) mixed in the ration and Lutofolone (0.5 mg/kg B.W.) orally via a bent stainless steel feeding tube, respectively, for 30 days (from the 15th till the 45th day old). Then these treated groups were left for another 15 days without any treatment. Blood samples were collected at 45 and 60 days old and used for biochemical studies, while liver and muscles were excised from each chicken and used to prepare tissue homogenate for estimation of hormonal residues (estrogen and progesterone). Both drugs caused a gain in body weight. They also increased several serum variables, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, creatine kinase (CK), creatinine and uric acid, and reduced total proteins, albumin and globulin levels at 30 days post-administration. Moreover, this study exhibited a significant increase in the levels of estrogen residues in the liver and muscle. Estrogen level was much higher in the liver than muscles. However, some of these findings were insignificant changed at 15 days post-stopping of the hormones. Data on the biochemical parameters and residue levels obtained from these results clearly indicate that anabolic agents may entail a special risk to the chickens and probably to the consumer.

β-Thalassemia: Genotypes and Phenotypes

β-Thalassemias are extremely heterogeneous at the molecular level. More than 200 disease-causing mutations have been identified. The majority of mutations are single nucleotide substitutions. Rarely, β-thalassemia results from gross gene deletion. The degree of globin chain imbalance is determined by the nature of the mutation of the βgene. β0 refers to the complete absence of production of β-globin on the affected allele. β+ refers to alleles with some residual production of β-globin (around 10%). In β++, the reduction in β-globin production is very mild. The broad spectrum of β-thalassemia alleles can produce a wide spectrum of different β-thalassemia phenotypes. In this chapter, we review the molecular basis of the marked heterogeneity of the thalassemia syndromes or in other words the genotype-phenotype relationship in β-thalassemia.