Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent ß-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial.

INTRODUCTION: Despite the improvement in medical management, many patients with transfusion-dependent ß-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent ß-thalassaemia with very high iron overload. METHODS AND ANALYSIS: This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent ß-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals. TRIAL REGISTRATION NUMBER: The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).

Patient size as a parameter for determining Diagnostic Reference Levels for paediatric Computed Tomography (CT) procedures.

INTRODUCTION: The paediatric radiation dose has never been studied in Sri Lanka, nor has a national diagnostic reference level (NDRL) established. Therefore, the primary aim of this study was to propose diagnostic reference levels (DRL) and achievable dose (AD) values for paediatric CT examinations based on size. METHODS: A total of 658 paediatric (0-15 years) non-contrast-enhanced (NC) studies of head, chest and abdomen regions performed during six months in two dedicated paediatric hospitals (out of the three such institutions in the country) were included. For head examinations, the dose indexes were analysed based on age, while for body examinations, both age and effective diameter (Deff) were used. The median and the third quartile of the pooled dose distribution were given as AD and NDRL, respectively. RESULTS: The AD ranges for the head, chest and abdomen regions based on CTDIvol were 45.8-57.2 mGy, 2.9-10.0 mGy and 3.8-10.3 mGy. The corresponding NDRL ranges were 45.8-95.8 mGy, 3.5-14.1 mGy and 4.5-11.9 mGy. The AD ranges based on SSDEdeff and deff were 3.5-9.6 mGy and 4.1-10.3 mGy in chest and abdomen regions. The corresponding NDRL were 4.5-14.1 mGy and 6.1-10.6 mGy. CONCLUSION: Other institutions can use the present study DRLs as a reference dose for paediatric CT. The AD values can be used as a baseline for target dose optimisations, reducing doses up to 90%.

Ultrasonographic length of morphologically-normal kidneys in children presented to a premier tertiary healthcare setting of Sri Lanka.

BACKGROUND: Accurate prediction of reference ranges of renal lengths facilitates clinical decision making. Currently a single renal-length-reference chart is used for both kidneys, which is solely based on the age of the child without adjusting for anthropometrics. Objective of the study is to assess the length of morphologically-normal kidneys ultrasonically and to build models to predict the renal lengths of children presenting at the Radiology Department of Lady Ridgeway Hospital for Children. METHODS: A descriptive cross sectional study was done among 424 children with 233 males and 191 females at the study setting. Study population included children undergoing abdominal ultrasound scans for indications not related to renal disease. Children with a family history of renal diseases or with morphologically-abnormal kidneys were excluded. Bipolar-lengths of kidneys, gender and anthropometrics were documented. Having tested for assumptions, Wilcoxon-signed rank test, Mann-Whitney U test and multiple linear regression were used. RESULTS: The mean (SD) bipor-length of right and left kidneys were 6.83 (1.43) and 7.05 (1.36) respectively (p < 0.001). Age, height and weight were significantly correlated with the renal lengths (p < 0.05). Until 16 months, there was a significant difference between the renal lengths between males and females (P < 0.05). Yet the association with gender was not significant from 17 months and in overall. Until 16 months, the best linear-regression equation (p < 0.001) for the left kidney was; 3.827 +  0.019(length in centimeters) +  0.141(weight in kilograms) - 0.023(age in months) - 0.347(for male sex). For the right kidney, it was; 3.888 + 0.020(length or height) + 0.121(weight) - 0.037(age) - 0.372 (for male sex). The respective R squares were 59.2 and 53.5% with VIF (Variance-Inflation-Factor) ranging from 1.06 to 2.08. From 17 months, best equation for left kidney (p < 0.001) was; 5.651+ 0.022(age) + 0.01(BMI). For right kidney it was; 5.336 + 0.022(age) + 0.012(BMI). The R squares were 62.5 and 66.1% with VIF being 1. CONCLUSIONS: The established models explain more variability for children above 17 months. Both renal lengths are affected significant by the body's' anthropometric parameters. For each kidney, separate normograms of renal lengths which are local-context-specific must be prepared. Further research must be promoted.