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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Mistakes in the management of iron deficiency anaemia: A narrative review(Taylor & Francis, 2024) Niriella, M.A.; Jayasena, H.; Withanachchi, A.; Premawardhena, A.INTRODUCTION Anaemia occurs due to an imbalance between erythrocyte production and loss. This imbalance can be due to ineffective erythropoiesis, blood loss or haemolysis. Whilst there are many causes for anaemia, iron deficiency anaemia (IDA) remains the predominant cause worldwide.AREAS COVERED: There have been many updated guidelines on the management of IDA in the past few years. As the reasons for IDA are many, evaluation requires thorough analysis and focused investigations. As an asymptomatic disease in the early stages, IDA can lead to many mistakes in its management. This review highlights potential mistakes in assessing and managing IDA and recommendations to avoid them.CONCLUSION The effective management of IDA necessitates a comprehensive and multidisciplinary approach. By recognising and addressing the common mistakes highlighted in this narrative review, healthcare professionals can improve patient outcomes, minimise complications, and enhance the overall quality of care.Item Direct correction of haemoglobin E β-thalassaemia using base editors(Nature Pub. Group, 2023) Badat, M.; Ejaz, A.; Hua, P.; Rice, S.; Zhang, W.; Hentges, L.D.; Fisher, C.A.; Denny, N.; Schwessinger, R.; Yasara, N.; Roy, N.B.A.; Issa, F.; Roy, A.; Telfer, P.; Hughes, J.; Mettananda, S.; Higgs, D.R.; Davies, J.O.J.Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE β-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any mutation causing severe β-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (β-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 90% in primary human CD34 + cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations.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 An attempt to study the behavior of plasma Hemoglobin in post transfusion iron chelated state in beta thalassemia major patients at Thalassemia Unit Kurunegala(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2021) Adikari, A.A.S.R.; Nawarathna, N.H.LA.; Fernando, K.M.I.; Abeypala, B.M.P.P.M.; Kottahachchi, D.U.; Gunathilaka, S.Introduction: Beta thalassemia major (pTM) patients require regular blood transfusions due to improper synthesis of normal hemoglobin. Objectives: The aim of this study is to make an attempt to examine the behavior of plasma hemoglobin of pTM patient in post transfusion iron chelated state. Methods: 145 patients from age 2-35 years (Male=l 13; Female=32) who were diagnosed with pTM selected for the study. Monthly haemoglobin values and 6-month Serum Ferritin (SF) values were obtained from their BHTs for two consecutive years. Correlations in between SF and haemoglobin were established using SPSS (version 20). The maximum and minimum pre-transfusion haemoglobin values (MaxPreHb and MinPreHb) were calculated for each month based on gender. Results: Most of the pre-transfusion haemoglobin values of patients lie within the 4-11 g/dl range and a statistically significant difference (p=0.021) is shown between MaxPreHb and MinPreHb. In gender wise analysis, it was shown that statistically significant differences were observed between MaxPreHb and MinPreHb of females (p=0.004) and males (p=0.013). The overall variation among MinPreHb (SD=0.81) is more compared with that of MaxPreHb (SD=0.53). The variation among MinPreHb of females and males (SD=0.71 and 1.75) is more compared with that of MaxPreHb (SD=0.40 and 1.75). However, there was no correlation between SF and haemoglobin. Conclusions: The data reveals, the group of haemoglobin around 5.0 g/dl indicates that those patients had not been compensated well by the blood transfusion. This may be due to excess haemolysis in that group. However, the other group of haemoglobin around 11.0 g/dl indicates the transfusion may have affected well.Item Global Burden of Haemoglobin Disorders(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2016) Rees, D.C.OBJECTIVES: 1. To describe the world distribution of haemoglobin disorders 2. To describe the health burden of haemoglobin disorders Haemoglobin disorders are the commonest, severe inherited disorders in the world, particularly prevalent in low- and middle-income countries. The two main conditions caused by mutations in globin genes are sickle cell disease (SCD), and thalassaemias. Approximately 300 000 children are born each year with sickle cell disease, with estimates suggesting this will reach 400 000 per year by 2050. The largest numbers of SCD births are estimated to occur in Nigeria (90 000 births/year), Democratic Republic of Congo (39 700 births/year) and India (44 000 births/year). Worldwide there are approximately 30 000 most of these occurring in Asia and the Middle East. The relative importance of haemoglobin disorders is increasing in many countries as deaths from infectious diseases decrease, and both thalassaemia and SCD are recognised as global health problems by the World Health Organisation. Antenatal and neonatal screening programmes are important in managing haemoglobinopathies and are established in some high-income countries, including UK, USA and parts of the Middle East. However there are very few national screening programmes in lower-income countries in which these conditions are most prevalent. Local screening programmes are established in areas of many countries and are revealing important information about the microdistribution of these conditions. In SCD, relatively simple measures, such as vaccination, penicillin prophylaxis, antimalarial measures and treatment of infections are thought to significantly reduce the otherwise very high childhood mortality, although these are not available in many areas. Hydroxyurea is relatively cheap, and has been shown to alter the natural history of SCD, although its role in Africa and India is yet to be established. The treatment of severe thalassaemia relies largely on the availability of safe blood transfusions and iron chelation, which are available in relatively few Asian countries unless a patient is able to pay. Stem-cell based treatments are becoming increasingly important, and although expensive may be cost-effective in some settings. Overall haemoglobin disorders cause significant morbidity and mortality across the world. More research is needed to define the prevalence and natural history of these conditions in different countries, and to develop clinical trials and interventions appropriate to low- and middle-income settings.