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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Deferoxamine, deferasirox, and deferiprone triple iron chelator combination therapy for transfusion-dependent β-thalassaemia with very high iron overload: a randomised clinical trial(Elsevier Ltd, 2024-10) Premawardhena, A.; Wanasinghe, S.; Perera, C.; Wijethilaka, M.N.; Rajakaruna, R.H.M.G.; Samarasinghe, R.A.N.K.K.; Williams, S.; Mettananda, S.BACKGROUND Many patients with β-thalassaemia die prematurely due to iron overload. In this study, we aim to evaluate the efficacy and safety of the triple combination of deferoxamine, deferasirox and deferiprone on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload.METHODS This open-label, randomised, controlled clinical trial was conducted at Colombo North Teaching Hospital, Sri Lanka. Transfusion-dependent β-thalassaemia patients with ferritin >3500 ng/mL were randomised 2:1 into intervention (deferoxamine, deferasirox and deferiprone) and control (deferoxamine and deferasirox) arms. Reduction in serum ferritin after six months was the primary outcome measure. Reduction in liver iron content, improvement in cardiac T2∗, and adverse effects were secondary outcome measures.FINDINGS Twenty-three patients (intervention-15, control-8) were recruited. 92% and 62% in the intervention and control arms showed a reduction in ferritin, respectively. The mean reduction of ferritin was significantly higher in intervention (−1094 ± 907 ng/mL) compared to control (+82 ± 1588 ng/mL) arm (p = 0.042). There was no statistically significant difference in the liver iron content in two arms. In the intervention arm, 67% improved cardiac T2∗ (mean change +6.72 ± 9.63 ms) compared to 20% in the control arm (mean change −3.00 ± 8.24 ms). Five patients discontinued deferiprone due to arthralgia, which resolved completely after stopping the drug.INTERPRETATION Triple combination therapy with deferoxamine, deferasirox and deferiprone is more efficacious in reducing iron burden measured by serum ferritin and showed a positive trend in reducing myocardial iron content in patients with transfusion-dependent β-thalassaemia with very high iron overload. Deferiprone has the disturbing side effect of reversible but severe arthropathy.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 Impact of acalypha indica (Kuppamenia) phytochemicals on glucose-6-phosphate dehydrogenase deficiency: two clinical case studies(College of Chemical Pathologists of Sri Lanka, 2024) Fernando, K.; Fernando, N.; Dayanath, B.K.T.P.; Williams, S.; Premawardhena, A.INTRODUCTION Acalypha indica, known as “kuppamenia” in Sinhala, plays a significant role in ayurvedic medicine in Sri Lanka. Despite its medicinal use, certain phytochemicals within the plant have been linked to oxidative stress-induced haemolysis in individuals deficient in glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. However, we know very little regarding those chemicals due to a dearth of literature. Here, we present two cases highlighting the impact of Acalypha indica ingestion on individuals with G6PD deficiency.CASE PRESENTATION Case 1: A 65-year-old man presented with jaundice, pallor, and haematuria after consuming “Kuppamenia mallum”. His peripheral blood picture showed bite cells and Heinz bodies. Positive Brewer’s test raised the clinical suspicion of G6PD deficiency. He received blood transfusions during the acute phase and was discharged upon improvement of symptoms. Low levels of G6PD enzyme at the follow-up visit confirmed the diagnosis. Case 2: A 61-year-old male presented with respiratory distress, jaundice and haematuria, accompanied by peripheral cyanosis and hypotension. He was admitted following four days of continuous ingestion of Acalypha indica. Peripheral oxygen saturation was low, and Heinz bodies were evident in the peripheral blood film. Blotting paper methaemoglobinaemia assessment revealed a level of 70%. Despite optimal medical management, he succumbed to a cardiac arrest on the fourth day of admission.DISCUSSION AND CONCLUSIONS Despite its antioxidant properties, Acalypha indica can precipitate acute haemolysis in G6PD-deficient individuals. Symptomatology and outcomes vary with the amount ingested, underscoring the necessity for research into identifying potentially toxic phytochemicals and their concentrations.Item Patients’ right to confidentiality and sharing information with colleagues: The dilemma in managing a patient with Munchausen syndrome – A case report(Ceylon College of Physicians, 2024) Welhenage, C.U.; Premawardhena, A.We report the case of a young woman with a “pyrexia of unknown origin” in the background of a history involving SLE, ocular toxoplasmosis and Ig A nephropathy. The history was narrated by her with precise details but there was no documentary proof of any previous admissions. She had a prolonged hospital stay and repeated hospital admissions for the same illness with extensive investigations including a PET scan. Once evidence for “factitious fever” was overwhelming she got herself discharged from hospital refusing psychiatric help. Close scrutiny revealed that she had got herself admitted to several hospitals in the Western Province subsequently, with the same complaint, with all clinicians investigating her extensively, sometimes including invasive procedures. The ethical dilemma faced by us relating to sharing her clinical details with a wider clinical group is discussed.Item Obesity, liver steatosis and metabolic syndrome: The hidden enemies in transfusion-dependent thalassaemia(Wiley-Blackwell, 2024) Padeniya, P.; Premawardhena, A.In their paper, the authors quantified liver iron concentration (LIC) and hepatic steatosis (HS) using MRI-T2* technology in transfusion-dependent thalassaemia (TDT) patients and healthy controls and found that the prevalence of HS among patients with TDT was 36.4%. In comparison with healthy controls, the hepatic fat fraction (FF) was significantly higher in the TDT population (p = 0.013). Active hepatitis C virus infection, body mass index (BMI) and LIC were independent predictors of HS. An inverse correlation between hepatic FF and high-density lipoprotein cholesterol (p = 0.042) and a significant association of high glycaemia level (p = 0.037) with higher hepatic FF and a significant relationship (p = 0.026) between HS and higher BMI (though in a 'lean' group of patients) in TDT patients indicated that 'metabolic syndrome' was present in this subset with TDT. The impact of metabolic syndrome on TDT, including cardiac disease unrelated to iron overload, needs further study. Commentary on: Ricchi et al. Liver steatosis in patients with transfusion-dependent thalassaemia. Br J Haematol 2024;204:2458-2467.Item Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent β-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial(BMJ Publishing Group Ltd, 2024) Premawardhena, A.; Perera, C.; Wijethilaka, M.N.; Wanasinghe, S.K.; Rajakaruna, R.H.M.G.; Samarasinghe, R.A.N.K.K.; Williams, S.; Mettananda, S.INTRODUCTION: Despite the improvement in medical management, many patients with transfusion-dependent β-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 β-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 β-thalassaemia are enrolled and randomized 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.Item GDF15 linked to maternal risk of nausea and vomiting during pregnancy(Nature Pub. Group, 2024) Fejzo, M.; Rocha, N.; Cimino, I.; Lockhart, S.M.; Petry, C.J.; Kay, R.G.; Burling, K.; Barker, P.; George, A.L.; Yasara, N.; Premawardhena, A.; Gong, S.; Cook, E.; Rimmington, D.; Rainbow, K.; Withers, D.J.; Cortessis, V.; Mullin, P.M.; MacGibbon, K.W.; Jin, E.; Kam, A.; Campbell, A.; Polasek, O.; Tzoneva, G.; Gribble, F.M.; Yeo, G.S.H.; Lam, B.Y.H.; Saudek, V.; Hughes, I.A.; Ong, K.K.; Perry, J.R.B.; Sutton, C.A.; Baumgarten, M.; Welsh, P.; Sattar, N.; Smith, G.C.S.; Charnock- Jones, D.S.; Coll, A.P.; Meek, C.L.; Mettananda, S.; Hayward, C.; Mancuso, N.; O'Rahilly, S.GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy (NVP) including its most severe form, Hyperemesis Gravidarum (HG), but a full mechanistic understanding is lacking [1-4]. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally-labelled GDF15 variant we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with beta-thalassemia, a condition where GDF15 levels are chronically high [5], report very low levels of NVP. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally-derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.Item Extensive systemic thrombo-embolism including intra-cardiac thrombosis mimicking an atrial myxoma in a patient with beta thalassaemia major - a case report(BioMed Central, 2023) Welhenge, C.; Ranasinghe, R.; Rajapakse, S.; Premawardhena, A.BACKGROUND: Sepsis and thrombo-embolic disease are well known complications of thalassemia major. Intracardiac thrombi are however rare and can lead to diagnostic dilemmas. CASE PRESENTATION: We report the case of a 20-year-old female splenectomised thalassaemia major patient with severe iron overload, who presented with life threatening sepsis associated with a liver abscess. Discovery of a large oscillating intra cardiac lesion on 2D echocardiogram confrmed by Contrast Enhanced Computed Tomography (CECT) chest in the right atrium extending from the left hepatic vein through the inferior vena cava complicated the clinical course. After a prolonged Intensive Care Unit (ICU) stay supported with antibiotics and anticoagulation, she recovered with evidence of resolution of the intra cardiac thrombus. CONCLUSIONS: Early recognition and prompt aggressive treatment of sepsis in patients with thalassemia is essential to prevent complications. Intracardiac thrombosis is a potentially treatable cause for an intra cardiac mass in patients with thalassemia major, which should not be missed.Item Hemoglobin E-beta-thalassemia: Progress report from the international study group(Blackwell Publishing, 2005) Premawardhena, A.; de Silver, S.; Arambepola, M.; Olivieri, N.F.; Vichinsky, E.P.; Merson, L.; Muraco, G.; Allen, A.; Fisher, C.; Peto, T.; Weatherall, D.J.A long-term observational study of Hb E-beta-thalassemia in Sri Lanka is beginning to define some of the genetic and environmental factors that are responsible for its remarkable phenotypic variability. In this population there is a very small difference between the steady-state hemoglobin levels between the mild and severe phenotypes, and it has been possible to stop transfusion in many of those who have been on long-term treatment of this kind. These preliminary observations, made over the last 7 years, provide directions for future research into this increasingly important disease.Item Examining depression and quality of life in patients with thalassemia in Sri Lanka(Wolters Kluwer - Medknow, 2019) Patel, P.; Beamish, P.; da Silva, T.L.; Kaushalya, D.; Premawardhena, A.; Williams, S.; Ravindran, A.V.BACKGROUND: With more effective treatments and improved outcomes in thalassemia, there is increasing focus on its psychological sequelae. Most published data on this topic are from high income countries and much less so from low and middle income countries, where thalassemia is more prevalent. AIM: The aim of this study was to systematically evaluate the psychiatric morbidity and quality of life in relation to demographic and illness related variables among Sri Lankan patients with thalassemia. METHODS: This cross sectional investigation was conducted at the University of Kelaniya Teaching Hospital in Sri Lanka. Patients with all forms of thalassemia, over 12 years of age, and in stable medical condition (n = 120) were recruited. Assessment tools included a general demographic questionnaire, the Beck Depression Inventory II, and the World Health Organization Quality of Life Measure–Brief. Statistical analysis was conducted using linear regressions, Chi squares, and analyses of variance. RESULTS: Lack of family support, longer duration of inpatient admission, and female gender were associated with higher depression scores and reduced quality of life. Environmental and social quality of life were positively correlated with levels of peer support in males, while increased support from religion correlated with lower depression scores and higher satisfaction with environmental and psychological quality of life in women. There was no association between the type of thalassemia and either depression or quality of life measures. CONCLUSION: Several factors may influence the psychological state and well being of patients with thalassemia in Sri Lanka. Specific service innovations (some gender specific) may help to address these factors to improve treatment outcome and well being.