Journal/Magazine Articles

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This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine

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Effects of Cinnamomum zeylanicum (Ceylon cinnamon) extract on lipid profile, glucose levels and its safety in adults: A randomized, double-blind, controlled trial
(Public Library of Science, 2025-01) Muthukuda, D.; De Silva, C. K.; Ajanthan, S.; Wijesinghe, N.; Dahanayaka, A.; Pathmeswaran, A.
BACKGROUND Cinnamon has been studied as a possible way to control blood glucose and serum cholesterol levels. However, there are no well-conducted randomized controlled trials that can accurately measure the lipid and glucose-lowering effects of Cinnamomum zeylanicum (C. zeylanicum) extract. This study primarily aimed to evaluate the effect of a standardized C. zeylanicum extract on serum low-density lipoprotein cholesterol (LDL-C) levels and secondarily on other lipid parameters (high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglycerides), glucose levels, anthropometric measures, blood pressure, and safety outcomes in individuals with an LDL level between 100-190mg/dL.MATERIALS AND METHODS This was a randomized, double-blinded, placebo-controlled clinical trial. Participants were allocated to either C. zeylanicum extract or placebo group (1:1 allocation ratio). They were advised to take two capsules per day (1000 mg/day, a dose based on prior clinical studies suggesting potential efficacy and safety). Reduction in LDL-C at 12 weeks (from the baseline value) was compared between the two groups using ANCOVA. A complete-case analysis was adhered to in analyzing the outcome data.RESULTS The mean age (SD) of the 150 participants was 50.4 (10.52) years, and 66% were females. Among the 127 participants assessed at 12 weeks, those in the C. zeylanicum extract arm had a lower LDL-C value than the placebo arm but the difference was not significant (the baseline adjusted mean difference was 6.05mg/dL; 95% CI: -2.43 to 14.52; p = 0.161). However, participants in the C. zeylanicum extract group showed significantly greater reductions in fasting blood sugar (FBS) levels (the baseline adjusted mean difference was 8.59mg/dL; 95% CI: 0.59 to 16.59; p = 0.036). There was a significant interaction effect between the supplement and participants' glycemic status, with individuals with type 2 diabetes mellitus (T2DM) who received C. zeylanicum extract experiencing a notable reduction in FBS levels (standardized coefficient: -63, 95% CI: -102 to -25; p = 0.002).CONCLUSIONS C. zeylanicum extract did not have significantly reduce LDL-C but demonstrated a significant FBS-lowering effect, particularly in individuals with T2DM, with a favorable safety profile.
Sex differences in stroke in a Sri Lankan cohort
(Karger, 2024-12) Ranawaka, U. K.; Mettananda, C. D.; Nugawela, M.; Pathirana, J.; Chandrasiri, J.; Jayawardena, C.; Amarasekara, D.; Hettarachchi, R.; Premawansa, G.; Pathmeswaran, A.
INTRODUCTION Stroke characteristics, subtypes, and risk factors in women may differ from men. Data on sex differences in stroke are scarce in developing countries, especially the South Asian region. We aimed to describe the sex differences in patients with stroke admitted to a tertiary care hospital in Sri Lanka. METHODS Consecutive patients with stroke enrolled in the Ragama Stroke Registry over 3 years (2020–2023) were studied. Sex differences in demographics, presentation delays, clinical characteristics, stroke subtypes, risk factors, stroke severity, and early functional outcomes were compared using χ2 test, independent sample t test and Wilcoxon rank-sum test. Associations of early functional dependence were studied using multiple logistic regression. RESULTS Of 949 patients with stroke, 387 (40.8%) were women, with a median age of 66 (interquartile range [IQR] 57–73) years compared to 63 (IQR 54–70) years in men (p < 0.001). Women had more ischaemic strokes (85.8% vs. 78.6% in men, p = 0.005). Swallowing difficulty (p = 0.039) and bladder involvement (p = 0.001) were more common in women, whereas dysarthria (p = 0.002) and cerebellar signs (p = 0.005) were more common in men. More women had hypertension (74.4% vs. 59.4%, p < 0.001) and diabetes (52.2% vs. 41.6%, p = 0.001), whereas smoking (0.3% vs. 35.1%, p < 0.001), alcohol use (0.3% vs. 55.0%, p < 0.001), and other substance abuse (0.8% vs. 5.2%, p < 0.001) were almost exclusively seen in men. No differences were noted in delays to hospital admission (delay ≥4.5 h: women 45.4% vs. men 41.3%, p = 0.222). There were no sex differences in the rates of CT scanning (women 100% vs. men 99.6%, p = 0.516) or thrombolysis for ischaemic stroke (women 7.8% vs. men 10.2%, p = 0.458), but more men received stroke unit care (women 37.2% vs. men 45.4%, p = 0.012). No differences were noted between sexes in the clinical (Oxfordshire classification, p = 0.671) or aetiological (TOAST criteria, p = 0.364) subtypes of stroke. Stroke severity on admission was similar between sexes (median NIHSS score; women 8.0 vs. men 8.0, p = 0.897). More women had a discharge Barthel index (BI) <60 than men (62.6% vs. 53.5%, p = 0.007), but female sex was not associated with BI <60 on multivariate logistic regression (p = 0.134). There was no difference in in-hospital mortality (women 5.9% vs. men 5.9%, p = 0.963). CONCLUSIONS Women with stroke in this Sri Lankan cohort were older, had different risk factor profiles and clinical stroke characteristics, and had more ischaemic strokes. Female sex was not independently associated with functional disability on discharge or in-hospital mortality.
Development and validation of a cardiovascular risk prediction model for Sri Lankans using machine learning.
(Public Library of Science, 2024-10) Mettananda, C.; Sanjeewa, I.; Arachchi, T.B.; Wijesooriya, A.; Chandrasena, C.; Weerasinghe, T.; Solangaarachchige, M.; Ranasinghe, A.; Elpitiya, I.; Sammandapperuma, R.; Kurukulasooriya, S.; Ranawaka, U.; Pathmeswaran, A.; Kasturiratne, A.; Kato, N.; Wickramasinghe, R.; Haddela, P.; De Silva, J.
INTRODUCTION AND OBJECTIVES Sri Lankans do not have a specific cardiovascular (CV) risk prediction model and therefore, World Health Organization(WHO) risk charts developed for the Southeast Asia Region are being used. We aimed to develop a CV risk prediction model specific for Sri Lankans using machine learning (ML) of data of a population-based, randomly selected cohort of Sri Lankans followed up for 10 years and to validate it in an external cohort.MATERIAL AND METHODS The cohort consisted of 2596 individuals between 40-65 years of age in 2007, who were followed up for 10 years. Of them, 179 developed hard CV diseases (CVD) by 2017. We developed three CV risk prediction models named model 1, 2 and 3 using ML. We compared predictive performances between models and the WHO risk charts using receiver operating characteristic curves (ROC). The most predictive and practical model for use in primary care, model 3 was named "SLCVD score" which used age, sex, smoking status, systolic blood pressure, history of diabetes, and total cholesterol level in the calculation. We developed an online platform to calculate the SLCVD score. Predictions of SLCVD score were validated in an external hospital-based cohort.RESULTS Model 1, 2, SLCVD score and the WHO risk charts predicted 173, 162, 169 and 10 of 179 observed events and the area under the ROC (AUC) were 0.98, 0.98, 0.98 and 0.52 respectively. During external validation, the SLCVD score and WHO risk charts predicted 56 and 18 respectively of 119 total events and AUCs were 0.64 and 0.54 respectively.CONCLUSIONS SLCVD score is the first and only CV risk prediction model specific for Sri Lankans. It predicts the 10-year risk of developing a hard CVD in Sri Lankans. SLCVD score was more effective in predicting Sri Lankans at high CV risk than WHO risk charts.
Antenatal oral glucose tolerance test abnormalities in the prediction of future risk of postpartum diabetes in women with gestational diabetes: Results from the living study
(Blackwell Publishing Asia, 2024) Gupta, Y.; Kapoor, D.; Lakshmi, J.K.; Praveen, D.; Santos, J.A.; Billot, L.; Naheed, A.; De Silva, H.A.; Gupta, I.; Farzana, N.; John, R.; Ajanthan, S.; Bhatla, N.; Desai, A.; Pathmeswaran, A.; Prabhakaran, D.; Teede, H.; Zoungas, S.; Patel, A.; Tandon, N.
OBJECTIVES To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria.METHODS This post-hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria.RESULTS We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow-up period of 1.8 (1.4-2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6-10.0)/100 women-years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval [CI], 1.18-2.54; p = .005) and 3.56 (95% CI, 2.46-5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70-4.00; p < .001), compared to isolated abnormal FPG.CONCLUSIONS Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.
Inhaled beclomethasone in the treatment of early COVID-19: a phase 2, double-blind, placebo-controlled, randomised trial
(The College, 2023) Mettananda, C,; Peiris, C.; Abeyrathna, D.; Gunasekera, A.; Egodage, T.; Danthanarayana, C.; Pathmeswaran, A.; Ranasinha, C.
No abstract available
Inhaled beclomethasone in the treatment of early COVID-19: a double-blind, placebo-controlled, randomised, hospital-based trial in Sri Lanka
(BMJ Publishing Group Ltd, 2023) Mettananda, C.; Peiris, C.; Abeyrathna, D.; Gunasekara, A.; Egodage, T.; Dantanarayana, C.; Pathmeswaran, A.; Ranasinha, C.
OBJECTIVES: To study if early initiation of inhaled beclomethasone 1200 mcg in patients with asymptomatic, mild or moderate COVID-19 reduces disease progression to severe COVID-19. DESIGN: Double-blinded, parallel-groups, randomised, placebo-controlled trial. SETTING: A hospital-based study in Sri Lanka. PARTICIPANTS: Adults with asymptomatic, mild or moderate COVID-19, presenting within the first 7 days of symptom onset or laboratory diagnosis of COVID-19, admitted to a COVID-19 intermediate treatment centre in Sri Lanka between July and November 2021. INTERVENTIONS: All participants received inhaled beclomethasone 600 mcg or placebo two times per day, for 10 days from onset of symptoms/COVID-19 test becoming positive if asymptomatic or until reaching primary endpoint, whichever is earlier. PRIMARY OUTCOME MEASURE: Progression of asymptomatic, mild or moderate COVID-19 to severe COVID-19. SECONDARY OUTCOME MEASURES: The number of days with a temperature of 38°C or more and the time to self-reported clinical recovery. RESULTS: A total of 385 participants were randomised to receive beclomethasone(n=193) or placebo(n=192) stratified by age (≤60 or >60 years) and sex. One participant from each arm withdrew from the study. All participants were included in final analysis. Primary outcome occurred in 24 participants in the beclomethasone group and 26 participants in the placebo group (RR 0.90 ; p=0.763). The median time for self-reported clinical recovery in all participants was 5 days (95% CI 3 to 7) in the beclomethasone group and 5 days (95% CI 3 to 8) in the placebo group (p=0.5). The median time for self-reported clinical recovery in patients with moderate COVID-19 was 5 days (95% CI 3 to 7) in the beclomethasone group and 6 days (95% CI 4 to 9) in the placebo group (p=0.05). There were no adverse events. CONCLUSIONS: Early initiation of inhaled beclomethasone in patients with asymptomatic, mild or moderate COVID-19 did not reduce disease progression to severe COVID-19. TRIAL REGISTRATION NUMBER: Sri Lanka Clinical Trials Registry; SLCTR/2021/017.
The incidence and risk factors of postpartum diabetes in women from Bangladesh, India and Sri Lanka (South Asia) with prior gestational diabetes mellitus: Results from the LIVING study
(Elsevier, 2023) Gupta, Y.; Kapoor, D.; Lakshmi, J.K.; Praveen, D.; Santos, J.A.; Billot, L.; Naheed, A.; de Silva, H.A.; Gupta, I.; Farzana, N.; John, R.; Ajanthan, S.; Bhatla, N.; Desai, A.; Pathmeswaran, A.; Prabhakaran, D.; Teede, H.; Zoungas, S.; Patel, A.; Tandon, N.; LIVING Collaborative Group
AIM: To study, the incidence and risk factors for postpartum diabetes (DM), in women with gestational diabetes mellitus (GDM) from South Asia (Bangladesh, India and Sri Lanka), followed for nearly two years after delivery. METHODS: Women with prior GDM diagnosed using IADPSG criteria were invited at 19 centres across Bangladesh, India and Sri Lanka for an oral glucose tolerance test (OGTT) following childbirth, and were enrolled in a randomized controlled trial. The glycaemic category (outcome) was defined from an OGTT based on American Diabetes Association criteria. RESULTS: Participants (n = 1808) recruited had a mean ± SD age of 31.0 ± 5.0 years. Incident DM was identified, between childbirth and the last follow-up, in 310 (17.1 %) women [incidence 10.75/100 person years], with a median follow-up duration of 1.82 years after childbirth. Higher age, lower education status, higher prior pregnancy count, prior history of GDM, family history of DM, and postpartum overweight/obese status were significantly associated with incident DM. Women in Bangladesh had a higher cumulative incidence of DM [16.49/100 person years] than in Sri Lanka [12.74/100 person years] and India [7.21/100 person years]. CONCLUSIONS: A high incidence of DM was found in women with prior GDM in South Asia, with significant variation between countries. Women from Bangladesh had a significantly higher pregnancy count, family history of DM and overweight/obese status, despite having significantly lower age, which could be responsible for their higher rates of DM. Registration of this study: The study was registered with the Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001), and ClinicalTrials.gov (NCT03305939).
Identification of patients with type 2 diabetes with non-alcoholic fatty liver disease who are at increased risk of progressing to advanced fibrosis: a cross-sectional study
(BMJ Publishing Group Ltd, 2023) Mettananda, C.; Egodage, T.; Dantanarayana, C.; Fernando, R.; Ranaweera, L.; Luke, N.; Ranawaka, C.; Kottahachchi, D.; Pathmeswaran, A.; de Silva, H.J.; Dassanayake, A.S.
INTRODUCTION: Identification of advanced hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) is important as this may progress to cirrhosis and hepatocellular carcinoma. The risk of hepatic fibrosis is especially high among patients with diabetes with NAFLD. Annual screening of patients with diabetes for fatty liver and calculation of Fibrosis-4 (FIB-4) score and exclusion of significant fibrosis with vibration-controlled transient elastography (VCTE) have been recommended. However, VCTE is expensive and may not be freely available in resource-limited settings. We aim to identify predictors of significant liver fibrosis who are at increased risk of progression to advanced liver fibrosis and to develop a prediction model to prioritise referral of patients with diabetes and NAFLD for VCTE. METHODS AND ANALYSIS: This cross-sectional study is conducted among all consenting adults with type 2 diabetes mellitus with NAFLD at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All patients get the FIB-4 score calculated. Those with FIB-4 ≥1.3 undergo VCTE (with FibroScan by Echosens). Risk associations for progression to advanced liver fibrosis/cirrhosis will be identified by comparing patients with significant fibrosis (liver stiffness measure (LSM) ≥8 kPa) and without significant fibrosis (LSM <8 kPa). A model to predict significant liver fibrosis will be developed using logistic regression. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (P/66/07/2021). Results of the study will be disseminated as scientific publications in reputable journals.
Alcohol use and alcoholic fatty liver disease: a prospective, communitybased study among adults in an urban community in Sri Lanka
(The Sri Lanka Medical Association, 2022) Niriella, M.A.; Kasturiratne, A.; Beddage, T.; de Silva, S.T.; Dassanayake, A.S.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.
Background: Data on alcoholic fatty liver (AFL) is limited. Therefore, we investigated alcohol use and AFL in a cohort of adults in an urban community in Sri Lanka. Methods: The study population (selected by age-stratified random sampling) was screened in 2007 (35-64 years) and re-evaluated in 2014. They were assessed by structured interviews, anthropometric measurements, liver-ultrasound, and biochemical and serological tests. AFL was diagnosed on ultrasound criteria, ‘unsafe’ alcohol consumption (Asian standards: males>14 units, females >7 units per week) and absence of hepatitis B/C markers. Controls were unsafe alcohol consumers who had no fatty liver on ultrasound. Results: 2985/3012 (99%) had complete data for analysis. 272/2985 (9.1%) were unsafe-drinkers in 2007 [males-270; mean-age-51.9, SD-8.0 years]. 86/272 (31.6%) had AFL [males-85; mean-age-50.2, SD-8.6 years]. Male gender [p<0.001], increased waist circumference (WC) [OR 4.9, p<0.01], BMI>23kg/m2 [OR 3.5, p<0.01] and raised alanine aminotransferase (ALT) [OR 2.8, p<0.01] were independently associated with AFL. 173/272 (63.6%) unsafe alcohol consumers from 2007 were re-evaluated in 2014. 134/173 had either had AFL or had changed to ‘safe’ or no alcohol consumption. 21/39 (53.8%) [males-21 (100%), meanage- 57.9, SD-7.9 years] who remained ‘unsafe’ alcohol users who had no fatty liver in 2007 developed AFL after 7-years (annual incidence 7.7%). On bivariate analysis, only male gender was associated with new-onset AFL. Of the 42 who had AFL at baseline but changed their drinking status from unsafe to safe or no alcohol, 6 had resolution of fatty liver in 2014. Conclusion: In this community-based study among adults from an urban community, unsafe alcohol use was found in 9.1%. Among unsafe alcohol users, the prevalence of AFL was 31.6% and the annual incidence of AFL was 7.7%. New-onset AFL was independently associated with male gender.
Measuring antenatal depressive symptoms across the world: A validation and cross-country invariance analysis of the Patient Health Questionnaire-9 (PHQ-9) in eight diverse low-resource settings
(American Psychological Association, 2022) Murray, A.L.; Hemady, C.L.; Do, H.; Dunne, M.; Foley, S.; Osafo, J.; Sikander, S.; Madrid, B.; Baban, A.; Taut, D.; Ward, C.L.; Fernando, A.; Thang, V.V.; Eisner, M.; Hughes, C.; Fearon, P.; Valdebenito, S.; Tomlinson, M.; Pathmeswaran, A.; Walker, S.
Measures that produce valid and reliable antenatal depressive symptom scores in low-resource country contexts are important for efforts to illuminate risk factors, outcomes, and effective interventions in these contexts. Establishing the psychometric comparability of scores across countries also facilitates analyses of similarities and differences across contexts. To date, however, few studies have evaluated the psychometric properties and comparability of the most widely used antenatal depressive symptom measures across diverse cultural, political, and social contexts. To address this gap, we used data from the Evidence for Better Lives Study-Foundational Research (EBLS-FR) project to examine the internal consistency reliability, nomological network validity, and cross-country measurement invariance of the nine-item version of the Patient Health Questionnaire (PHQ-9) in antenatal samples across eight low-resource contexts. We found that the PHQ-9 scores had good internal consistency across all eight countries. Correlations between PHQ-9 scores and constructs conceptually associated with depression were generally consistent, with a few exceptions. In measurement invariance analyses, only partial metric invariance held and only across four of the countries. Our results suggest that the PHQ-9 yields internally consistent scores when administered in culturally diverse antenatal populations; however, the meaning of the scores may vary. Thus, interpretation of PHQ-9 scores should consider local meanings of symptoms of depression to ensure that context-specific conceptualizations and manifestations of antenatal depressive symptoms are adequately reflected. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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