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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 The first reported case of co-infection of imported hepatitis E and Plasmodium falciparum malaria in Sri Lanka(Sri Lankan Society for Microbiology, 2023) Senarathne, S.; Rajapakse, S.; de Silva, H.J.; Seneviratne, S.; Chulasiri, P.; Fernando, D.Global travel and tourism, especially across tropical countries, may lead to importation of malaria and other infectious diseases into Sri Lanka. This case report describes the first co-infection of imported hepatitis E and Plasmodium falciparum malaria in a tourist diagnosed in Sri Lanka. The patient was initially diagnosed with uncomplicated P. falciparum malaria and was started on treatment with oral Artemisinin-based Combination Therapy (ACT). Deterioration of hepatic enzymes and hyperbilirubinaemia despite the rapid parasitological response to antimalarials led to further investigation and diagnosis of co-infecting hepatitis E in this patient. The importance of clinicians being vigilant on travel associated co-infections is highlighted to ensure early diagnosis and better patient management.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 First co-infection of malaria and hepatitis E diagnosed in Sri Lanka(Sri Lanka Medical Association, 2023) Senarathne, S.; Rajapakse, S.; de Silva, H.J.; Seneviratne, S.; Chulasiri, P.; Fernando, D.INTRODUCTION: Imported malaria cases continue to be reported in Sri Lanka. Similarly, hepatitis E is also considered a travel associated imported disease in Sri Lanka. This is a report of the first co-infection of malaria and hepatitis E in Sri Lanka. OBJECTIVES: A 21-year-old European who visited Sri Lanka after a 2 months stay in India, was admitted to hospital with fever, vomiting, abdominal pain, and dark-coloured urine on the 4th day after his arrival. On examination, he had splenomegaly but no hepatomegaly. He had thrombocytopaenia; 89% neutrophils; 9% lymphocytes; elevated liver enzymes and hyperbilirubinaemia. Urine was positive for bile pigment. METHODS: Considering his travel history to India, he was tested for malaria. The rapid diagnostic test became positive for Plasmodium falciparum while microscopy showed P. falciparum ring stages with a parasite density of 120/μl. He was treated as for uncomplicated P. falciparum malaria with oral Artemisinin-based Combination Therapy. The patient became fever-free and blood smears became negative after 13 hours following 2 doses of antimalarials. RESULTS: However, his liver functions were further deranged with apparent jaundice (ALT: 250 U/L; AST: 175 U/L; ALP: 130 U/L; GGT: 179 U/L; total bilirubin: 10.65 mg/dL; direct bilirubin: 8.08 mg/dL; indirect bilirubin: 2.57 mg/dL). Further blood tests detected hepatitis E-specific IgM antibodies. He was treated with oral ursodiol but no specific antiviral was given. Following the completion of antimalarials, he was discharged from the hospital upon clinical recovery. CONCLUSION: Clinicians should be vigilant on travel-associated co-infections in patients who are diagnosed with imported malaria.Item Cardiac emergencies in obstetrics(Taylor and Francis Group, 2021) Padumadasa, S.; Rajapakse, S.No abstract availableItem A case of hypotension and heart rate changes on rechallenge with a low dose of clozapine with no apparent secondary cause(Sri Lanka College of Psychiatrists, 2022) Harshini, M.L.; Fernando, A.I.W.; Abayawickrama, H.M.T.S.; Ikram, M.I.N.; Rajapakse, S.; Hapangama, A.Clozapine is known to cause innocuous as well as severe and or fatal cardiovascular side effects. These side effects are commonly reported at the initiation of clozapine therapy. We report a patient who was stable on clozapine for several years but in whom we had to withhold clozapine for medical reasons and subsequently developed significant hypotension and heart rate changes when rechallenged with a small dose of clozapine.Item Development of an in-house ELISA as an alternative method for the serodiagnosis of leptospirosis(Elsevier, 2021) Niloofa, R.; Karunanayake, L.; de Silva, H.J.; Premawansa, S.; Rajapakse, S.; Handunnetti, S.BACKGROUND: Leptospirosis is most often clinically diagnosed and a laboratory test with high diagnostic accuracies is required. METHODOLOGY: IgM and IgG-ELISAs using Leptospira antigens were established and evaluated in relation to the Microscopic Agglutination Test (MAT). Antigen preparation consisted either saprophytic Leptospira biflexa to detect genus specific antibodies (genus-specific ELISA) or a pool of five most prevalent Leptospira interrogans serovars in Sri Lanka to detect serovar specific antibodies (serovar-specific ELISA). IgM and IgG immune responses in severe and mild leptospirosis patients (n = 100 in each group) were studied. RESULTS: ELISAs showed high repeatability and reproducibility. Serovar-specific IgM-ELISA showed sensitivity of 80.2% and specificity of 89%; genus-specific IgM-ELISA showed sensitivity of 83.3% and specificity of 91%. Serovar and genus-specific IgG-ELISA showed sensitivities of 73.3% and 81.7%, and specificities of 83.33%. Commercial IgM-ELISA showed sensitivity and specificity of 79.2% and 93% respectively. Commercial IgG-ELISA showed sensitivity, specificity of 50% and 96.7% respectively. IgM levels observed in mild and severe leptospirosis (ML & SL) patients were significantly higher than healthy control (HC) group, having absorbance mean of 0.770, 0.778 and 0.163 respectively. In contrast, SL patients had significantly higher mean anti-leptospiral IgG levels compared to both ML and HC groups (0.643, 0.358 and 0.116 respectively; ANOVA, P < 0.001). Presence of anti-leptospiral IgG above OD 0.643 optical density (OD) at 1:100 could predict high risk of severe disease. CONCLUSION: Serovar-specific In-House ELISAs could be used for the laboratory diagnosis of leptospirosis in endemic settings. Observed high levels of anti-leptospiral IgG suggest its value as a predictor for disease severity. KEYWORDS: IgM and IgG antibodies; In-House ELISA; Leptospirosis; Sero-diagnosis.Item Severe hyponatremia-induced stress cardiomyopathy: A case report and review of literature(Hindawi Pub. Corp., 2020) Perera, I.; Rajapakse, S.; de Silva, S.T.ABSTRACT: Takotsubo or stress cardiomyopathy is a non ischemic disease affecting the myocardium, which presents with typical features of myocardial ischemia. Although the presentation with acute central chest pain and shortness of breath mimics acute myocardial ischemia, there is an absence of actual disruption of cardiac blood supply via the coronaries due to acute plaque rupture or vascular spasm. The underlying pathophysiology of this clinical entity remains largely unclear, but a definite association with physical or emotional stress has been well established, hence the term "stress cardiomyopathy." The list of potential triggers continues to grow as the disorder is increasingly detected by clinicians and cardiologists, with better clinical insight and improved availability of cardiac investigations. We report a patient with Takotsubo cardiomyopathy associated with severe hyponatremia.Item Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.(The Lancet. Global health., 2019) Lung, T.; Jan, S.; de Silva, H.A.; Guggilla, R.; Maulik, P.K.; Naik, N.; Patel, A.; de Silva, A.P.; Rajapakse, S.; Ranasinghe, G.; Prabhakaran, D.; Rodgers, A.; Salam, A.; Selak, V.; Stepien, S.; Thom, S.; Webster, R.; Lea-Laba, T.; TRIUMPH Study Group.BACKGROUND: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. METHODS: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. FINDINGS: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (-28·67 to 5714·24) per DALY averted over a 10-year period. INTERPRETATION: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease.Item Fixed low-dose triple combination Antihypertensive Medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: A Randomized Clinical Trial(American Medical Association, 2018) Webster, R.; Salam, A.; de Silva, H.A.; Selak, V.; Stepien, S.; Rajapakse, S.; Amarasekara, N.; Amarasena, N.; Billotm, L.; de Silva, A.P.; Fernando, M.; Guggilla, R.; Jan, S.; Jayawardena, J.; Maulik, P.K.; Mendis, S.; Mendis, S.; Munasinghe, J.; Naik, N.; Prabhakaran, D.; Ranasinghe, G.; Thom, S.; Thisserra, N.; Senaratne, V.; Wijekoon, S.; Wijeyasingham, S.; Rodgers, A.; Patel, A.; TRIUMPH Study GroupIMPORTANCE: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. OBJECTIVE: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. INTERVENTIONS: A once-daily fixed-dose triple combination pill (20 mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone) therapy (n = 349) or usual care (n = 351). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion achieving target systolic/diastolic BP (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 months. Secondary outcomes included mean systolic/diastolic BP difference during follow-up and withdrawal of BP medications due to an adverse event. RESULTS: Among 700 randomized patients (mean age, 56 years; 58% women; 29% had diabetes; mean baseline systolic/diastolic BP, 154/90 mm Hg), 675 (96%) completed the trial. The triple combination pill increased the proportion achieving target BP vs usual care at 6 months (70% vs 55%, respectively; risk difference, 12.7% [95% CI, 3.2% to 22.0%]; P < .001). Mean systolic/diastolic BP at 6 months was 125/76 mm Hg for the triple combination pill vs 134/81 mm Hg for usual care (adjusted difference in postrandomization BP over the entire follow-up: systolic BP, -9.8 [95% CI, -7.9 to -11.6] mm Hg; diastolic BP, -5.0 [95% CI, -3.9 to -6.1] mm Hg; P < .001 for both comparisons). Overall, 419 adverse events were reported in 255 patients (38.1% for triple combination pill vs 34.8% for usual care) with the most common being musculoskeletal pain (6.0% and 8.0%, respectively) and dizziness, presyncope, or syncope (5.2% and 2.8%). There were no significant between-group differences in the proportion of patient withdrawal from BP-lowering therapy due to adverse events (6.6% for triple combination pill vs 6.8% for usual care). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate hypertension, treatment with a pill containing low doses of 3 antihypertensive drugs led to an increased proportion of patients achieving their target BP goal vs usual care. Use of such medication as initial therapy or to replace monotherapy may be an effective way to improve BP control.Item Effect of antimicrobial agents on inflammatory cytokines in acute Leptospirosis(American Society for Microbiology, 2018) Fernando, N.; de Silva, R.; Hadunnetti, S.M.; Karunanayake, L.; de Silva, N.L.; de Silva, H.J.; Rajapakse, S.; Premawansa, S.The aim of this study was to assess the inflammatory cytokine response and possible association with antimicrobial treatment with penicillin, ceftriaxone, and doxycycline in acute leptospirosis. In the early acute stage, interleukin-10 (IL-10) levels were higher in mild cases than in severe cases (P = 0.01). IL-6 and IL-8 levels were low in patients who received >5 antimicrobial doses (P < 0.01). IL-8 levels were negatively correlated with the number of ceftriaxone doses administered (r = -0.315; P = 0.031). Further studies are needed to evaluate the possible downregulation of proinflammatory cytokines by ceftriaxone in leptospirosis.
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