Patient preference for deferasirox film-coated versus dispersible tablet formulation: a sequential-design phase 2 study in patients with thalassemia.

Iron chelation therapy (ICT) is the mainstay of treatment in patients with thalassemia requiring blood transfusions. This phase 2 JUPITER study evaluated patient preference between film-coated tablet (FCT) and dispersible tablet (DT) in transfusion-dependent thalassemia (TDT) or non-TDT (NTDT) patients treated with both formulations in a sequential manner. The primary endpoint was patient-reported preference for FCT over DT, while secondary outcomes included patient reported outcomes (PROs) evaluated by overall preference, and by age, thalassemia transfusion status, and previous ICT status. Out of 183 patients screened, 140 and 136 patients completed the treatment periods 1 and 2 of the core study, respectively. At week 48, the majority of patients preferred FCT over DT (90.3 vs. 7.5%; difference of percentage: 0.83 [95% confidence interval (CI), 0.75-0.89; P < 0.0001]). FCT scored better on secondary PROs and showed less severe gastrointestinal symptoms than DT, except in the change of modified Satisfaction with Iron Chelation Therapy (mSICT) preference scores, which were similar for both the formulations. Patients with TDT had stable ferritin levels, while it showed a downward trend up to week 48 in patients with NTDT on deferasirox treatment. Overall, 89.9% of patients reported ≥ 1 adverse event (AE), of which 20.3% experienced ≥ 1 serious AE. The most common treatment-emergent AEs were proteinuria, pyrexia, urine protein/creatinine ratio increase, diarrhea, upper respiratory tract infections, transaminase increase, and pharyngitis. Overall, this study reinforced the observations from the previous study by showing a distinct patient preference for FCT over DT formulation and further supported the potential benefits of life-long compliance with ICT.

First Report of aacC5-aadA7Δ4 Gene Cassette Array and Phage Tail Tape Measure Protein on Class 1 Integrons of Campylobacter Species Isolated from Animal and Human Sources in Egypt.

Campylobacter species are common commensals in the gastrointestinal tract of livestock animals; thus, animal-to-human transmission occurs frequently. We investigated for the first time, class 1 integrons and associated gene cassettes among pan drug-resistant (PDR), extensively drug-resistant (XDR), and multidrug-resistant (MDR) Campylobacter species isolated from livestock animals and humans in Egypt. Campylobacter species were detected in 58.11% of the analyzed chicken samples represented as 67.53% Campylobacter jejuni(C. jejuni) and 32.47% Campylobacter coli (C. coli). C. jejuni isolates were reported in 51.42%, 74.28%, and 66.67% of examined minced meat, raw milk, and human stool samples, respectively. Variable antimicrobial resistance phenotypes; PDR (2.55%), XDR (68.94%), and MDR (28.5%) campylobacters were reported. Molecular analysis revealed that 97.36% of examined campylobacters were integrase gene-positive; all harbored the class 1 integrons, except one possessed an empty integron structure. DNA sequence analysis revealed the predominance of aadA (81.08%) and dfrA (67.56%) alleles accounting for resistance to aminoglycosides and trimethoprim, respectively. This is the first report of aacC5-aadA7Δ4 gene cassette array and a putative phage tail tape measure protein on class 1 integrons of Campylobacter isolates. Evidence from this study showed the possibility of Campylobacter-bacteriophage interactions and treatment failure in animals and humans due to horizontal gene transfer mediated by class 1 integrons.

Selenium and Vitamin E as antioxidants in chronic hemolytic anemia: Are they deficient? A case-control study in a group of Egyptian children.

Accelerated oxidative damage is one of the hallmarks in both sickle cell disease (SCD) and thalassemia major (TM). A decreased antioxidant level is found in both diseases. Our study was carried out to evaluate the variation in serum levels of Selenium and Vitamin E among a group of transfusion dependant Egyptian SCD and TM patients, further more to correlate these levels with iron overload status or transfusion requirements. A case-control study was conducted at the Cairo University Pediatric Hospital to assess the serum levels of Selenium using Atomic Absorption Spectrometer and Vitamin E using commercially available ELISA Kit in transfusion dependent children, 30 with beta thalassemia and 30 with SCD in a steady state aged from 6 to 18 years, these findings were compared to 30 age/sex matched healthy controls. Our results revealed a depleted antioxidants level in the studied group of Egyptian children with TM and SCD relative to healthy controls (P < 0.05). A significant positive correlation was found between Vitamin E levels and ferritin (r = 0.26, p = 0.047) in SCD and TM patients. Nonsignificant correlation was detected between serum Selenium and Vitamin E. Moreover, values of these antioxidants did not correlate with indices of hemolysis nor with those of inflammation in chronically transfused TM and SCD patients.

Acute hemolytic anemia as an initial presentation of Wilson disease in children.

BACKGROUND: Wilson disease (WD) is an inherited disorder of copper metabolism. Hemolytic anemia in WD occurs in up to 17% of patients at some point during their illness. AIM: To screen for WD among children presenting with hemolytic anemia. METHODOLOGY: Twenty cases (mean age, 8.8 ± 3.9 y) with Coombs-negative hemolytic anemia, attending the hematology clinic of children hospital, Cairo University, were screened for WD by serum ceruloplasmin level, 24 hours urinary copper before and after D-penicillamine challenge test, and slit-lamp examination for detecting Kayser-Fleischer rings. RESULTS: No case had low ceruloplasmin, whereas bilateral Kayser-Fleischer rings was detected in 5% of our cases. Urinary copper was elevated in 5% before and in 40% after D-penicillamine challenge test. According to the scoring system used, 1 case had definite WD and 7 cases were likely to have WD. These 8 (40%) cases were referred to as group B. Group B had a significantly lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and reticulocytes (P=0.04, 0.001, 0.04, and 0.04, respectively) and a significantly higher urinary copper after penicillamine (P=0.000) when compared with group A (unlikely WD). CONCLUSION: WD is not uncommon in children with hemolytic anemia after exclusion of other common causes.

Blood transfusion among thalassemia patients: A single Egyptian center experience.

BACKGROUND: Although red cell transfusions are lifesavers for patients with thalassemia, they are responsible for a series of complications and expose the patients to a variety of risks. MATERIAL AND METHODS: This cross-sectional study included 464 Egyptian beta(ß) thalassemia major patients whose age ranged between 10 months and 31 years (mean 10.2 ± 6.6 years). All patients were subjected to thorough history taking with special emphasis on blood transfusions regarding rate of blood transfusion, type of received blood, and history of previous transfusion reactions in addition to type of chelation and compliance to iron chelation therapy and history of diabetes. Serum ferritin and pretransfusion hemoglobin assessment were done for all patients. RESULTS: The mean pretransfusion hemoglobin level was 5.7 ± 1.16 g/dl. Allergic reactions were observed in 3.9% of the patients during the period of the study, while the history of previous allergic reaction was given by 72% of the patients. Deferiprone showed better compliance (58.6%) than deferoxamine (26.3%). The prevalence of diabetes was 10.1% among the studied group. On comparing diabetics to nondiabetics, serum ferritin, transfusion intervals, and age were statistically higher among diabetics (P<0.001). CONCLUSION: Lower pretransfusion hemoglobin and high rate of prevalence of diabetes, in addition to better compliance to deferiprone than deferoxamine, were detected among the patients.

Apolipoprotein E gene polymorphism and the risk of left ventricular dysfunction among Egyptian ß-thalassemia major.

In Egypt, ß-thalassemia is the most common hereditary hemolytic anemia. Cardiac dysfunction, secondary to iron overload with formation of oxygen free radicals, is the most common cause of death in ß-thalassemia patients. This study was designed to determine whether the allelic genotype of apolipoprotein E (Apo E), which exhibits antioxidant properties, could represent a genetic risk factor for the development of left ventricular (LV) dysfunction in ß-thalassemia major. Fifty Egyptian ß-thalassemia major patients were subjected to echocardiography to assess LV function. Apo E genotyping by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was done for all patients in addition to 50 age and sex matched healthy control subjects. Patients were classified into three groups. Group I and II were clinically asymptomatic. Group II subjects had evidence of LV dilatation, while Group III patients had clinical and echocardiographic findings of LV failure. Apo E4 allele was significantly higher among Group II and III than in controls. In conclusion, Apo E4 allele can be considered as a genetic risk factor for LV dysfunctions in ß-thalassemic patients. It could be used as predictive indicator for additional risk of LV failure, particularly in asymptomatic patients with LV dilatation, requiring a closer follow-up, to prevent further disease progression.

The effect of reducing repetition time TR on the measurement of liver R2 for the purpose of measuring liver iron concentration.

The effects of reducing the pulse repetition time from 2500 ms to 1000 ms when using spin-density-projection-assisted R2-magnetic resonance imaging for the purpose of measuring liver iron concentration were evaluated. Repeated liver R2 measurements were made using both protocols on 60 subjects with liver iron concentrations ranging from 0.5 to 48.6 mg Fe (g dry tissue)(-1). The mean total scan time at repetition time 1000 ms was 42% of that at repetition time 2500 ms. The repeatability coefficients for the two protocols were not significantly different from each other. A systematic difference in the measured R2 using each protocol was found indicating that an adjustment factor is required when one protocol is used to replace the other. The 95% limits of agreement between the two protocols were not significantly different from their repeatability coefficients indicating that the protocols can be interchanged without any significant change in accuracy or precision of liver iron concentration measurement.