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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Cardiac emergencies in obstetrics(Taylor and Francis Group, 2021) Padumadasa, S.; Rajapakse, S.No abstract availableItem 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.Item A pilot study on comparison of rapid immunodiagnostics for confirmation of leptospirosis(Sri Lanka Medical Association, 2012) Eugene, E.J.; Wickramasinghe, S.A.; Kalugalage, T.L.; Rodrigo, C.; Wickremesinghe, H.; Dikmadugoda, N.; Somaratne, P.; de Silva, H.J.; Rajapakse, S.; Handunnetti, S.M.INTRODUCTION: In Sri Lanka, leptospirosis is mostly diagnosed on clinical grounds. Serological confirmation is not obtainable during the acute stage of the illness. There is a need for rapid immunodiagnostics for confirmation of leptospirosis. Two immunodiagnostic assays, ie: enzyme linkedimmnnosorbent assay (ELISA) and immunochromatographic technique Leptocheck-WB test (LCT) areused to detect leptospira specific IgM antibodies which are prevalent in early stages of acute infections. AIMS: To compare the efficacy of these two rapid immunodiagnostic assays with the microscopic agglutination assay (MAT) to determine their applicability. Methods: A set of sera (n=83) collected in 2010 for which MAT titres were available was used to perform IgMELISAandLCT. RESULTS: Positivity for LCT and IgM ELISA were 55.4% and 48.2% respectively, and both assays detected acute infection by day 3 of the illness. MAT> 400 was used as the reference standard. For LCT, the overall sensitivity, specificity, accuracy, PPV and NPV (86.5%, 75.0%, 79.6%, 69.6% and 89.4% respectively) were higher compared to the respective values for IgM ELISA (50.0%, 62.3%, 57.1%, 50.0%, 62.3%). The highest of these values were observed during the first week for LCT and during the second week for IgM ELISA. The highest agreement was observed between LCT and MAT>400 (p=0.568) and there was a good agreement between LCT and IgM ELISA (p=0.520). CONCLUSIONS: The high sensitivity and specificity, ease of use, and non-requirement of specialized skills and equipment makes LCT a good choice for screening, while IgM ELISA is an appropriate test for confirming acute leptopsirosis.Item Clinico-epidemiological characteristics, treatment and outcomes of patients with confirmed Leptospirosis in a Sri Lankan healthcare setting(Sri Lanka Medical Association, 2015) Rajapakse, S.; Weeratunga, P.N.; Rodrigo, C.; Sriharan, S.; Niloofa, M.J.R.; Fernando, N.; de Silva, H.J.; Karunanayake, L.; Premawansa, S.INTRODUCTION AND OBJECTIVES: Leptospirosis is a zoonotic infection caused by spirochaetes of the genus Leptospira, with humans being affected as incidental hosts. Leptospirosis is endemic in Sri Lanka. There is paucity of prospective data on the clinico-epidemiological characteristics, treatment profiles and outcomes of patients with ieptospirosis in Sri Lanka. METHOD: This was a prospective cross sectional study of patients, over 12 years of age, with a diagnosis of ieptospirosis based on the WHO surveillance criteria with subsequent laboratory confirmation, presenting to three hospitals in the Western province of Sri Lanka. RESULTS: Of a total of 178 patients, males (84.3%) between the ages of 40-49 years were more likely to be affected. 51.7% were direct admissions and 47.8% were transfers. Exposure to water potentially contaminated with rat urine was seen in the majority (71.9%). A significant proportion of patients developed acute kidney injury (66.9%). Penicillin was the most commonly used antibiotic for treatment (47.2%), however more than one antibiotic was used in 43.3%. The use of chemoprophylaxis by the patients was low (1.1%). Hemodialysis was needed for 36.5%. Recovery was seen in 71.3%, 2.8% died, 10.1% were transferred out and 15.8% were lost to follow-up. On discharge, 70.6% had been treated for severe leptospirosis. Mean length of hospital stay was 7.5 days (±5.1). CONCLUSION: The incidence of severe leptospirosis with organ dysfunction is higher in patients presenting to hospitals in the .Western province. Males aged 40-49 are most commonly affected. More than two thirds of the patients developed acute kidney Injury. Chemoprophylaxis rates were low.Item A diagnostic model for Leptospirosis for use in resource limited settings(Sri Lanka Medical Association, 2015) Rajapakse, S.; Weeratunga, P.N.; Rodrigo, C.; Sriharan, S.; Niloofa, M.J.R.; Fernando, N.; de Silva, H.J.; Karunanayake, L.; Premawansa, S.INTRODUCTION AND OBJECTIVES: Leptospirosis is a zoonotic infection with significant morbidity and mortality. In this prospective study, we attempted to develop a model for diagnosis of leptospirosis. METHOD: Data was extracted from a prospective multicentre study. All patients with a suspected diagnosis of leptospirosis based on the WHO surveillance criteria were recruited. A derivation cohort and a validation cohort were selected. Positive MAT was used as the gold standard and significant associations in the derivation cohort were selected for construction of a multivariate regression model. Adjusted odds ratios were extracted for significant variables. ROC curves were generated. RESULTS: A total of 592 patients were included with 450 (180 confirmed leptospirosis) in the derivation cohort and 142 (52 confirmed leptospirosis) in the validation cohort. The variables in the final model were: history of exposure to possible source of leptospirosis (OR=2.878;95% Cl=1.527-5.425;p=0.001), serum creatinine>150u.mol/L (OR =2.742; 95% CN1.474-5.101; p=0.001), neutrophil differential percentage (on day 3 of illness) > 82.8% of total WBC count (OR 2.063; 95% Cl = 1.109 - 3.837; p =0.022), serum bilirubin > 27 U/L (OR = 1.767;95%CI 0.968 - 3.226; p=0.050) and platelet count (on day 3 of illness)< 85,000/mm3 (OR=2.350; 95%CI=1.281 -4.313;p=0.006). The Nagelkerke R2 was 0.654. ROC analysis demonstrated a diagnostic model score >14 to have a sensitivity of 80% and a specificity of 60% in the diagnosis of leptospirosis against MAT as the gold standard. CONCLUSION: This proposed diagnostic model for diagnosis of leptospirosis is of potential value to clinicians treating acute febrile illness in areas with limited diagnostic facilities.Item Clinical and laboratory associations of severity in a Sri Lankan cohort of patients with serologically confirmed Leptospirosis - a prospective study(Sri Lanka Medical Association, 2015) Rajapakse, S.; Weeratunga, P.N.; Rodrigo, C.; Sriharan, S.; Niloofa, M.J.R.; Fernando, N.; de Silva, H.J.; Karunanayake, L.; Premawansa, S.; Handunnetti, S.INTRODUCTION AND OBJECTIVES: Leptospirosis is a zoonotic infection of significant morbidity and mortality. This study elucidates the markers of severity in a cohort of Sri Lankan patients with serologically confirmed leptospirosis. METHOD: Prospectively recruited patients presenting to three healthcare institutions in the Western province of Sri Lanka with serological confirmation of leptospirosis with the microscopic agglutination test were included. Data regarding the socio-deruographic profile, clinical presentation, complications and biochemical parameters were recorded. Univariate associations and subsequent multivariate logistic regression models were constructed with severity as the dependent variable. RESULTS: A total of 232 patients were included. Majority were male (86.6%). Severe disease was noted in 68.5%. Significant clinical associations of severe disease included fever > 38.8°C on presentation (p=0.008), age>40 yrs; (p = 0.033), muscle tenderness (p=0.04) and tachycardia on admission (p=0.05). Laboratory associations of severe disease were highest white cell count > 12,350/mm3 (p<0.001) and < 7900/mm3 (p = 0.009), highest neutrophil percentage > 84% {p < 0.001). Hemoglobin > 11.2g/dL (p<0.001) and < 10.2 (p<0.001), packed cell volume > 33.8% (p <0.001) and <29.8% (p <0.001), lowest platelet count <63,500/mm3 (p = 0.01), highest ALT > 70 IU/L {p = 0.02) and hyponatremia with sodium <131mEq/L (p=0.004) On multivariate analysis, PCV < 29.8 (P = 0.011; adjusted OR =3.750; Cl = 1.394 - 10.423), ALT >70 P =0.044 adjusted OR =2.639; Cl =1.028-6.774 and hyponatremia< 131 (p=0.019 adjusted OR=6.413; Cl=1.353 -30.388) were found to be independent associations of severe disease. CONCLUSION: Severity associations were demonstrated with both clinical and laboratory parameters.Item Clinical and laboratory associations of severity in a Sri Lankan cohort of patients with serologically confirmed leptospirosis: a prospective study(Oxford : Oxford University Press, 2015) Rajapakse, S.; Weeratunga, P.; Niloofa, M.J.; Fernando, N.; Rodrigo, C.; Maduranga, S.; de Silva, N.L.; de Silva, H.J.; Karunanayake, L.; Handunnetti, S.BACKGROUND: Leptospirosis results in significant morbidity and mortality. This study elucidates markers of severity in a cohort of Sri Lankan patients. METHODS: Patients presenting to three healthcare institutions in the Western province of SriLanka with leptospirosis serological confirmed by the microscopic agglutination test (MAT) were included. Prospective data regarding demographic, clinical and laboratory parameters was extracted. Univariate associations and subsequent multivariate logistic regression models were constructed. RESULTS: The study included 232 patients, with 68.5% (159) demonstrating severe disease. Significant associations of severe disease at a significance level of p<0.05 were fever >38.8°C on presentation, age >40 years, muscle tenderness, tachycardia on admission, highest white cell count >12 350/mm(3) and <7900/mm(3), highest neutrophil percentage >84%, haemoglobin >11.2 g/dL and <10.2 g/dL, packed cell volume (PCV) >33.8% and <29.8%, lowest platelet count <63 500/mm(3), highest alanine transaminase (ALT) >70 IU/L and hyponatremia with sodium <131mEq/L. On multivariate analysis, PCV <29.8% (p=0.011; OR 3.750; CI: 1.394-10.423), ALT >70 IU/L (p=0.044; OR 2.639; CI: 1.028-6.774) and hyponatremia <131mEq/L (p=0.019; OR 6.413; CI: 1.353-30.388) were independent associations of severe disease. CONCLUSIONS: Severity associations were demonstrated with both clinical and laboratoryparameters. There is a need for novel biomarkers for prediction of severity in leptospirosis. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.Item Serum nitrite levels in Sri Lankan patients with leptospirosis(Elsevier, Singapore, 2012) Gunaratna, R.I.; Handunnetti, S.M.; Bulathsinghalage, M.R.C.; Somaratne, P.; Jayanaga, A.; de Silva, H.J.; Rajapakse, S.OBJECTIVE: To determine whether blood nitrite levels are elevated in patients with leptospirosis.METHODS: Male patients fulfilling clinical and epidemiological criteria for a diagnosis of leptospirosis were recruited. Those with MAT titre of ≤400 together with those seroconverting to a titer of ≤200 were included in the analysis. Serum nitrite levels were measured in these patients and age, sex matched healthy controls. RESULTS: Patients from 3 hospitals (n=75) were screened during a 3 month period from 28th June to 3rd September 2009, of whom 20 were eligible for the study. Serum nitrite levels were found to be significantly higher in patients with acute leptospirosis [n=20, (0.359±0.229)μ M] compared to controls [(n=13,(0.216±0.051)μ M](P=0.014). A significant correlation was also observed between the MAT titre and the day of illness (r = 0.547; P<0.0001). CONCLUSIONS: Serum nitrite levels are higher in patients with acute leptospirosis compared to age and sex matched controls. No correlation could be assessed with severity of illness, as sample size was inadequate to determine this