RESUMEN
Drug-resistant epilepsy presents significant challenges in treating epileptic patients, leading to recurrent seizures and necessitating the use of polypharmacy with anti-epileptic drugs. Both of these conditions contribute to increased oxidative stress, which is detrimental to the brain. The aim of this study was to determine the role of vitamins C and E in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients. This was a double-blinded, randomized clinical trial with a placebo, parallel design, and block randomization. The subjects were drug-resistant epileptic patients aged 1-18 years who received routine treatment. Randomization was performed on 100 patients who were divided into the treatment or placebo groups. The patients received a combination of vitamin C (100 mg/day) and vitamin E (200 IU/day for those <5 years or 400 IU/day for those ≥5 years) or a placebo for eight weeks. Malondialdehyde (MDA) levels and seizure frequency were measured prior to and after the intervention. A total of 42 and 46 patients were followed till the end of the study in the intervention and placebo groups, respectively. Our data indicated that the MDA levels prior to treatment were not significantly different between the treatment and placebo groups (0.901 vs 0.890 mmol/mL, p=0.920) and were significantly reduced after the treatment in both the treatment group (p<0.001) and placebo group (p=0.028). The changes in MDA levels (between post- and pre-treatment) were also not significantly different between the two groups (p=0.181). Our per-protocol analysis indicated that the reduction in seizure frequency was significantly higher in the treatment group compared to the placebo group (95% vs 35%, p<0.001), with 92% and 60% relative and absolute risk reduction, respectively. The intention-to-treat analysis also indicated that the reduction in seizure frequency was significantly higher in the intervention group than in the control group (80% vs 32%, p<0.001), with relative and absolute risk reduction of 70% and 48%, respectively. There was no significant relationship between changes in MDA levels and seizure frequency in either group. In conclusion, vitamins C and E could reduce seizure frequency and, therefore, could be considered as adjuvant therapy in drug-resistant epileptic patients.
Asunto(s)
Antioxidantes , Ácido Ascórbico , Epilepsia Refractaria , Estrés Oxidativo , Vitamina E , Humanos , Estrés Oxidativo/efectos de los fármacos , Masculino , Femenino , Método Doble Ciego , Ácido Ascórbico/uso terapéutico , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacología , Epilepsia Refractaria/tratamiento farmacológico , Antioxidantes/uso terapéutico , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Adolescente , Vitamina E/administración & dosificación , Vitamina E/farmacología , Vitamina E/uso terapéutico , Niño , Preescolar , Malondialdehído , Lactante , Convulsiones/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/farmacología , Anticonvulsivantes/administración & dosificaciónRESUMEN
Indonesia is located along the 'Thalassemia Belt' and a hotspot for hemoglobinopathies. Around 3.0-10.0% of the population carry ß-thalassemia (ß-thal) and 2.6-11.0% of the population carry α-thalassemia (α-thal). It is estimated that around 2500 babies are born with ß-thal major (ß-TM) each year. At present, the cornerstone of treatment for ß-TM in Indonesia remains supportive, including blood transfusions and iron chelation therapy. Hemovigilance systems in some cities are poor and it increases the risk of transfusion-transmitted infections and transfusion reactions. The availability of iron chelators remains uncertain, even in some rural areas, iron chelators do not exist. The poor adherence to iron chelation therapy and maintaining pretransfusion hemoglobin (Hb) levels above 9.0 g/dL are still a major issue in Indonesia. The cost of blood transfusion and iron chelation are covered by national health insurance. In line with the rise of life expectancy, the financial burden of thalassemia in Indonesia is increasing sharply. Thus, optimizing preventive programs may be the most suitable option for the current thalassemia condition in Indonesia.
Asunto(s)
Reacción a la Transfusión , Talasemia alfa , Talasemia beta , Humanos , Indonesia/epidemiología , Hierro , Quelantes del Hierro/uso terapéutico , Talasemia beta/epidemiología , Talasemia beta/terapiaRESUMEN
BACKGROUND: Pharmacokinetic (PK) studies of low-dose prophylaxis (LDP) of coagulation factor VIII (FVIII) in children with severe haemophilia A (SHA) are scarce. OBJECTIVE: This study aims to investigate the PK profile of children with SHA receiving LDP of FVIII. METHODS: Paediatric patients receiving FVIII infusions (10 IU/kg twice weekly) were included. PK profiles were estimated using the Web Accessible Population Pharmacokinetic Service for Haemophilia (WAPPS-Haemo). The primary outcomes were the terminal half-life (t1/2 ), concentration-time profile, and time to reach an FVIII level of < 1%. The secondary outcome was the suggested dosing interval of FVIII prophylaxis based on the individual PK profile. RESULTS: Twenty-five patients were recruited; their mean age was 12.3 ± 3.0 years. The t1/2 differed among patients receiving LDP of FVIII twice weekly, with a median of t1/2 was 14.8 h (IQR 12.6-16). The median time to reach an FVIII level of < 1% was 73.8 h (IQR 58.8-80.3). Most patients could maintain a trough level of FVIII > 1% longer than 48 h. At 72-96 h, patients needed a second dose of FVIII infusion because the FVIII level was < 1%. The suggested dosing interval of FVIII prophylaxis ranged from daily to every 96 h, depending on the individual PK profile. CONCLUSION: Our study identified inter-individual differences in the PK parameters using LDP of FVIII twice weekly. The inter-individual results in different dosing intervals advise the timing of LDP. Estimating individual PK parameters enables the identification of the optimal prophylaxis frequency to prevent bleedings.
Asunto(s)
Hemofilia A , Hemostáticos , Adolescente , Niño , Factor VIII/farmacocinética , Hemofilia A/complicaciones , Hemorragia/prevención & control , Hemostáticos/uso terapéutico , Humanos , IndonesiaRESUMEN
AIM: to describe non-spesific and specific immune response profile in Indonesian thalassemia major with and without splenectomy. METHODS: this study was held at Thalassaemia Centre, Cipto Mangunkusumo Hospital Jakarta on September 2013-February 2014. A comparative cross sectional study was conducted in healthy, thalassemia major aged more than 12 year and seronegative HIV. They were matched in age and sex for splenectomised and non-splenectomised groups, analysing the non-spesific immune response (neutrophil count and phagocytosis) and specific immune response (count and function of cellular immunity). Infection episodes were also analized as immune response in vivo parameter. RESULTS: splenectomised thalassemia major showed increased neutrophil count but significantly decreased non-spesific immune response (neutrophil phagocytosis). Spesific immune response of splenectomised group presented significantly higher absolute lymphocyte, lymphocyte T, CD4+ and CD8+ counts compared to non-splenectomised thalassemia major (p<0.05). Ratio CD4+/CD8+ were similar in these groups. Serum marker of activated cellular imunity function (IL-2 and TNF-) were similar among two groups. Mild infection episodes on splenectomised and non-splenectomised group were 2.02 (ranged 0 to 12) times and 0.81 (ranged 0 to 8) times (p=0.004), respectively. Severe infection on splenectomised group were sepsis for 2 weeks and diarrhea for 1 week, whereas on non-splenectomised group was typhoid fever for 4 days. CONCLUSION: there were significant differences on immune response among thalassemia major patients. Splenectomised thalassemia major showed a greater degree of susceptibility to infections than non-splenectomised thalassemia major.
Asunto(s)
Esplenectomía , Talasemia beta/inmunología , Adolescente , Adulto , Biomarcadores/sangre , Recuento de Linfocito CD4 , Niño , Estudios Transversales , Femenino , Humanos , Inmunidad Celular , Indonesia , Interleucina-2/sangre , Masculino , Neutrófilos/metabolismo , Fagocitosis , Factor de Necrosis Tumoral alfa/sangre , Adulto Joven , Talasemia beta/sangre , Talasemia beta/cirugíaRESUMEN
Approximately 6% of patients with thalassemia receiving deferiprone develop neutropenia. Present practice is to monitor absolute neutrophil count (ANC) weekly and to interrupt treatment at the first sign of neutropenia, lest continuation lead to progressive neutrophil reduction. In a 6-month study evaluating the safety and efficacy of a liquid form of deferiprone in 100 children, ANC was initially checked weekly for all patients. For individuals experiencing mild neutropenia, deferiprone was continued but monitoring was increased to daily until resolution. Therapy was to be suspended only if the episode was prolonged or if it worsened. Four patients experienced single episodes of mild neutropenia, and two others each experienced two episodes. All eight episodes resolved within 4-7 d despite continued therapy. (One patient later developed agranulocytosis and had treatment terminated.) This study showed that not all cases of mild neutropenia during deferiprone therapy develop into agranulocytosis, and suggests that many may not be caused by deferiprone. Transient declines in ANC to levels defined as neutropenic are common even in healthy individuals, particularly children; and it could be that the frequent monitoring of ANC mandated during deferiprone therapy may reveal cases of transient neutropenia that would otherwise have gone undetected and resolved on their own without clinical consequences. In patients with thalassemia, several factors increase the probability of a transient fall in ANC. These findings raise the question of whether deferiprone should be routinely stopped in cases of mild neutropenia, provided that such patients have their ANC monitored more frequently during the neutropenic episode.