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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 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 Mutational analysis of driver and non-driver mutations of Philadelphia chromosome-negative myeloproliferative neoplasms;diagnosis and recent advances in treatment(Science Publications, 2024) Afolabi, B.O.; Riwaz, A.; Weerasena, J.; Williams, S.; Denipitiya, T.; Somawardana, B.; Faizan, M.; Galhena, B.P.Myeloproliferative neoplasms (MPNs) are hematological disorders affecting myeloid stem cells. They are classified as Philadelphia (Ph) chromosome positive-chronic myeloid leukemia, and Ph-negative polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia, juvenile myelomonocytic leukemia, and MPN unclassifiable. This review is mainly focused on the Ph-negative MPNs namely, PV, ET, and PMF. These affect both males and females with a slight male predominance, with patients mainly presenting in the seventh decade. Patients often present with thrombotic events resulting in complications that lower survival rates. The major driver mutations that have been identified in MPNs are JAK2 Exon 14, JAK2 Exon 12, MPL Exon 10, and CALR Exon 9. The importance of these driver mutations gives due recognition to their inclusion into the 2022 diagnostic criteria of the MPN WHO Classification. However, other non-driver mutations have also been reported, especially in triple-negative cases. These mutations lead to downstream constitutive activation of the JAK/STAT signaling pathway, as well as the MAPK, and PI3K/Akt pathways. Insights into the molecular pathogenesis of MPN and its association with JAK2, CALR, and MPL mutations have identified JAK2 as a rational therapeutic target. Thus, as an approach to MPN therapy, JAK2 inhibitors, such as ruxolitinib, have been shown to effectively inhibit JAK2, and are currently in clinical trials in combination with other drug classes. This review comprehensively examines the molecular markers of the main Ph-negative MPNs, as well as diagnosis and treatment options.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 Persistent, poorly responsive immune thrombocytopenia secondary to asymptomatic COVID-19 infection in a child(Hindawi, 2023) Mettananda, C.; Williams, S.Immune thrombocytopenic purpura (ITP) secondary to asymptomatic COVID-19 infection, especially in children, is not reported. Furthermore, persistent, treatment-resistant ITP secondary to COVID-19 is not reported. We report a previously healthy 14-year-old Asian boy who developed secondary ITP following an asymptomatic COVID-19 infection and is having a relapsing and remitting cause with poor response to immunosuppressants even after 21 months following the diagnosis. This case emphasizes the importance of testing for COVID-19 in newly diagnosed ITP patients and the need for follow-up platelet counts in patients who recover from COVID-19 as it may follow into developing secondary ITP yet being asymptomatic until you present with a bleeding complication of ITP. The poor response to standard immunosuppression warrants more understanding of the pathophysiology of persistently low platelets following COVID-19 infection. Long-term sequelae of the disease highlight the importance of getting vaccinated for COVID-19 despite COVID-19 being no longer a global emergency.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.Item Acceptability of a web-based character strengths module for early adolescent school children(Postgraduate Institute of Medicine University of Colombo, 2023) Chandradasa, M.; Williams, S.; Sumanasiri, S.; Selliah, S.; Gunarathne, P.; Paric, A.; Ravindran, N.; Kuruppuarachchi, K.A.L.A; Ravindran, A.BACKGROUND: Frequent socio-political conflicts in the past decades have adversely affected the well-being of youth in Sri Lanka. There is a need to support youth development, mitigate past trauma, and promote social harmony. School-based interventions to improve character development, emotional regulation, and tolerance have good evidence and may benefit adolescents in Sri Lanka. Our objective was to develop a novel character strength program in Sinhala to promote Leadership, Empathy, Altruism, Personal Growth, and Social Responsibility (LEAPS). This program consists of ten web-based modules and is facilitated by teachers. This initial evaluation focuses on the first module and its acceptability among students and teachers. METHOD: Program modules were developed by a child and adolescent psychiatrist with the support of mental health and educational experts. The first module was piloted among grade 8 students (12-14 years) and teachers of two schools in the Gampaha District. It was designed to be interactive and contains various cultural activities and questions. On completion, participants gave feedback online via Likert scales. Ethical approval for the study was obtained from the Faculty of Medicine, University of Kelaniya. RESULTS: A total of 115 students and 66 teachers participated. Overall, more than 95% of students and teachers found the module appropriate and suitable. The students had more favourable ratings for the module compared to the teachers on aspects of understanding the content (p<0.001), ability to complete by self (p<0.001), suitability to age (p<0.001), shorter time for completion (p<0.001) and suitability of the design (p<0.001). Both groups suggested that the pictures and activities be increased. CONCLUSIONS: Teaching character strengths using a web-based intervention was well accepted by adolescent students and teachers in Sri Lanka.Item Transient severe thrombocytopenia with SARS-Cov-2 (COVID-19) infection in pregnancy(Sri Lanka college of Obstetricians & Gynaecologists, 2021) Jayawardane, I.A.; Piyadigama, I.; Solangaarachchi, H.; Williams, S.A 24-weeks pregnant woman in her 2nd pregnancy presented with mild COVID symptoms and new onset rapidly progressive severe thrombocytopenia with a nadir of 20×109/L. She did not have any bleeding manifestations and the platelet counts recovered over 3 days without the need of steroids or immunoglobulin treatment. COVID-19 infection may cause transient severe thrombocytopenia, and this has not been previously reported in second trimester of pregnancy. We speculate the cause to be immune mediated. Other causes for severe thrombocytopenia were excluded after comprehensive investigations. This raise concerns on thromboprophylaxis and anticoagulant use in early pregnancies infected with COVID-19. Assessing the platelet counts at least two occasions few days apart of an infected patient may be a safer approach if continuing anticoagulants.Item Impact of COVID-19 on the mental health of frontline and non-frontline healthcare workers in Sri Lanka(The Sri Lanka Medical Association, 2021) Baminiwatta, A.; de Silva, S.; Hapangama, A.; Basnayake, K.; Abayaweera, C.; Kulasinghe, D.; Kaushalya, D.; Williams, S.INTRODUCTION: Healthcare workers (HCWs) are at risk of mental health problems during a pandemic. Being stationed at the frontline or not may have implications on their mental health. OBJECTIVES: The aims of this study were to assess depression, anxiety and stress among HCWs, to explore differences between frontline and non-frontline workers, and to investigate associated factors. METHODS: In this cross-sectional study, frontline and non-frontline HCWs were recruited from a COVID-19 screening hospital in Sri Lanka. Mental health impact was assessed using Depression, Anxiety and Stress Scale (DASS-21). Sociodemographic data and perceptions of social and occupational circumstances were gathered. Categorical variables were analyzed using Chi square and logistic regression. Odds ratios were calculated for the effect of different perceptions on psychological morbidity. RESULTS: A total of 467 HCWs participated, comprising 244 (52.2%) frontline and 223 (47.8%) non-frontline workers, with female preponderance (n=341, 77%). Prevalence of depression, anxiety and stress among HCWs were 19.5%, 20.6%, 11.8%, respectively. Non-frontline group showed a higher prevalence of depression (27% vs. 11%, p<0.001), anxiety (27% vs. 14%, p=0.001) and stress (15% vs. 8%, p=0.026). Being married, having children, living with family and higher income were associated with better psychological outcomes. Perceived lack of personal protective equipment, inadequate support from hospital authorities, greater discrimination, and lack of training to cope with the situation predicted poor mental health outcomes, and non-frontline HCWs were more likely to hold such perceptions. CONCLUSION: Addressing factors leading to negative psychological outcomes in HCWs should be a key concern during this pandemic. KEYWORDS: COVID-19, Mental health, Hhealthcare workers, Frontline, Depression, Anxiety, StressItem Ethics in Haematology (Editorial)(The Sri Lanka College of Haematologists, 2019) Williams, S.No abstract available