Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study.(Elsevier Ltd, 2022) Premawardhena, A.P.; Ediriweera, D.S.; Sabouhanian, A.; Allen, A.; Rees, D.; de Silva, S.; Perera, W.; Katugaha, N.; Arambepola, M.; Yamashita, R.C.; Mettananda, S.; Jiffry, N.; Mehta, V.; Cader, R.; Bandara, D.; St Pierre, T.; Muraca, G.; Fisher, C.; Kirubarajan, A.; Khan, S.; Allen, S.; Lamabadusuriya, S.P.; Weatherall, D.J.; Olivieri, N.F.Background: Worldwide, haemoglobin E β-thalassaemia is the most common genotype of severe β-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. Methods: In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. Findings: 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 μg/L (vs concentration ≤1300 μg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival. Interpretation: Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival.Item Non-adherence to chelation therapy and associated psychosocial factors among transfusion-dependent thalassaemia patients in Kandy, Sri Lanka(Sri Lanka College of Paediatricians, 2021) Baminiwatta, A.; Gunathilake, R.; Arambepola, S.; Arambepola, M.BACKGROUND: Poor adherence to iron chelation may underlie the detrimental levels of iron overload previously reported among transfusion-dependent thalassaemia (TDT) patients in Sri Lanka. Given the many challenges faced by these patients and families, psychosocial factors may have a significant impact on medication adherence. OBJECTIVE: To assess chelation adherence among TDT patients and explore associated psychosocial factors. METHOD: TDT patients, aged over 4 years, admitted for blood transfusion to a tertiary care hospital, as well as their mothers, were recruited. Medication adherence was assessed using a questionnaire adapted from Brief Adherence Rating Scale. Serum ferritin (SF) values were recorded as objective measures of non-adherence. Mental health status of patients and their mothers was assessed using Strengths and Difficulties Questionnaire (SDQ) and General Health Questionnaire-30 (GHQ) respectively. Associated psychosocial factors were analysed using multiple linear regression. RESULTS: Fifty-two patients aged 4 to 28 years participated. Thirty-four (65%) were female. The average adherence rate was 90%. One fifth of patients had an adherence percentage less than 80%. The mean ferritin level was 3260 ng/ml, whereas 46.2% of patients had SF levels exceeding 2500ng/ml. SF levels correlated positively with non-adherence (r=0.34, 95%CI: 0.071-0.606, p=0.014). Based on multivariate analysis, increasing age and lower SDQ score of patient, lower educational level and greater GHQ-30 score of mother were independent predictors of higher SF levels, but not of adherence rates. CONCLUSIONS: In the paediatric unit of National Hospital, Kandy, 46% of patients had SF levels >2500 ng/ml. There was a significant correlation between SF levels and medication non-adherence (r=0.34, p=0.014). On multivariate analysis, increasing age and lower SDQ score of the patient, lower educational level and greater GHQ-30 score of the mother were independent predictors of higher SF levels, but not of adherence rates.Item A Cost-of-illness analysis of β-Thalassaemia major in children in Sri Lanka - experience from a tertiary level teaching hospital.(BioMed Central., 2020) Reed-Embleton, H.; Arambepola, S.; Dixon, S.; Maldonado, B. N.; Premawardhena, A.; Arambepola, M.; Khan, J. A. M.; Allen, S.BACKGROUND: Sri Lanka has a high prevalence of β-thalassaemia major. Clinical management is complex and long-term and includes regular blood transfusion and iron chelation therapy. The economic burden of β-thalassaemia for the Sri Lankan healthcare system and households is currently unknown. METHODS: A prevalence-based, cost-of-illness study was conducted on the Thalassaemia Unit, Department of Paediatrics, Kandy Teaching Hospital, Sri Lanka. Data were collected from clinical records, consultations with the head of the blood bank and a consultant paediatrician directly involved with the care of patients, alongside structured interviews with families to gather data on the personal costs incurred such as those for travel. RESULTS: Thirty-four children aged 2-17 years with transfusion dependent thalassaemia major and their parent/guardian were included in the study. The total average cost per patient year to the hospital was $US 2601 of which $US 2092 were direct costs and $US 509 were overhead costs. Mean household expenditure was $US 206 per year with food and transport per transfusion ($US 7.57 and $US 4.26 respectively) being the highest cost items. Nine (26.5%) families experienced catastrophic levels of healthcare expenditure (> 10% of income) in the care of their affected child. The poorest households were the most likely to experience such levels of expenditure. CONCLUSIONS: β-thalassaemia major poses a significant economic burden on health services and the families of affected children in Sri Lanka. Greater support is needed for the high proportion of families that suffer catastrophic out-of-pocket costs. KEYWORDS: Children; Cost-of-illness; Sri Lanka; Thalassaemia.Item A nationwide survey of hospital-based thalassemia patients and standards of care and a preliminary assessment of the national prevention program in Sri Lanka(Public Library of Science, 2019) Premawardhena, A.P.; Mudiyanse, R.; de Silva, S.T.; Jiffry, N.; Nelumdeniya, U.; de Silva, U.; Lamabadusuriya, S.P.; Pushpakumara, K.; Dissanayaka, R.; Jansz, M.; Rifaya, I.; Navarathne, U.; Thirukumaran, V.; Arambepola, M.; Bandara, W.D.; Vaidyanatha, U.; Mendis, D.; Weerasekara, K.; de Silva, N**.; Kumara, D.K.S.; Amarasena, S.D.; Hemantha, K. K.; Refai, M.A.C.M.; Silva, I.; Hameed, N.; Rajiyah, F.; Mettananda, S.; Allen, A.; Weatherall, D. J.; Oliveri, N. F.OBJECTIVES:Our aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme.METHODS:This cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records.RESULTS: We collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous β-thalassemia, 360 patients (20.3%) had hemoglobin E β-thalassemia, and 50 patients (2%) had sickle β-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with β-thalassaemia varied between 45-55, with little evidence of reduction over 19 years. CONCLUSIONS:Central coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.Item The variable phenotypes of haemoglobin D in Sri Lankan patients(Sri Lanka Medical Association, 2006) Premawardhena, A.; Arambepola, M.; Weatherall, D.INTRODUCTION: There are only few reports of the occurrence of the variant haemoglobin, haemoglobin D Punjab (β 121 Glu-Gln) in Sri Lanka and its clinical spectrum has not been well documented. MATERIALS AND METHODS: During the clinical study of patients attending the thalassaemia clinic at Teaching Hospital Kurunegala we identified several individuals with haemoglobin D, some of whom had co-inherited it with other haemoglobin disorders. They were diagnosed using High Performance Liquid Chromatography (Bio Rad, USA) and later confirmed by polymerase chain reaction. CLINICAL STUDIES: Family 1: (Hb D-p thalassaemia) Describes a family with two individuals with haemoglobin D- β thalassaemia. Both were mildly anaemic but had severe hypochromasia and microcytosis. They were otherwise well. Family 2: (Hb D- Hb S disease) The propositus was an eight year old girl who presented with several episodes of sickling crises. Parents were carriers for Hb S and Hb D. Family 3: (Hb D- Hb E disease) The propositus was an individual with Hb E- Hb D disease. She was clinically well and the only abnormality was severe hypochromasia and microcytosis. DISCUSSION: Hb D when co-inherited with Hb E or thalassaemia does not appear to cause clinically significant disease. The co-inheritance of Hb D with Hb S, however, results in severe disease leading to sickling crises. Even though Hb D commonly does not cause severe disease, knowledge of its occurrence is important as the hypochromasia and microcytosis associated with it may lead to unnecessary iron therapy.Item Interaction of malaria with a common form of severe thalassemia in an Asian population(National Academy of Sciences, 2009) O Donnell, A.; Premawardhena, A.; Arambepola, M.; Samaranayake, R.; Allen, S.J.; Peto, T.E.; Fisher, C.A.; Cook, J.; Corran, P.H.; Olivieri, N.F.; Weatherall, D.J.In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and beta thalassemia. The management of this disease is particularly difficult because of its extreme clinical diversity; although some genetic and adaptive factors have been identified as phenotypic modifiers, the reasons remain unclear. Because the role of the environment in the course of severe thalassemia has been neglected completely and because malaria due to both Plasmodium falciparum and Plasmodium vivax has been prevalent in Sri Lanka, we carried out a pilot study of patients with HbE beta thalassemia that showed high frequencies of antibodies to both parasite species and that 28.6% of the children had DNA-based evidence of current infection with P. vivax. Malarial antibodies then were assessed in patients with HbE beta thalassemia compared with those in age-matched controls. There was a significant increase in the frequency of antibodies in the thalassemic patients, particularly against P. vivax and in young children. There was also a higher frequency in those who had been splenectomized compared with those with intact spleens, although in the latter it was still higher than that in the controls. The thalassemic patients showed significant correlations between malaria antibody status and phenotype. Patients with HbE beta thalassemia may be more prone to malaria, particularly P. vivax, which is reflected in their clinical severity. Because P. vivax malaria is widespread in Asia, further studies of its interaction with HbE beta thalassemia and related diseases are required urgently as a part of ongoing thalassemia control programs.