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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Reduced efficacy of blood pressure lowering drugs in the presence of diabetes mellitus-results from the TRIUMPH randomised controlled trial
(Nature Publishing Group, 2023) Gnanenthiran, S.R.; Webster, R.; de Silva, A.; Maulik, P.K.; Salam, A.; Selak, V.; Guggilla, R.K.; Schutte, A.E.; Patel, A.; Rodgers, A.; TRIUMPH Study Group
We investigated whether diabetes mellitus (DM) affects the efficacy of a low-dose triple combination pill and usual care among people with mild-moderate hypertension. TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomised controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients were randomised to a once-daily low-dose triple combination polypill (telmisartan-20mg/amlodipine-2.5 mg/chlorthalidone-12.5 mg) or usual care. This analysis compared BP reduction in people with and without DM, both in the intervention and control groups over 24-week follow-up. Predicted efficacy of prescribed therapy was calculated (estimation methods of Law et al.). The trial randomised 700 patients (56 ± 11 yrs, 31% DM). There was no difference in the number of drugs prescribed or predicted efficacy of therapy between people with DM and without DM. However, the observed BP reduction from baseline to week 24 was lower in those with DM compared to non-diabetics in both the triple pill (25/11 vs 31/15 mmHg, p ≤ 0.01) and usual care (17/7 vs 22/11 mmHg, p ≤ 0.01) groups, and these differences remained after multivariable adjustment. DM was a negative predictor of change in BP (β-coefficient -0.08, p = 0.02). In conclusion, patients with DM experienced reduced efficacy of BP lowering therapies as compared to patients without DM, irrespective of the type of BP lowering therapy received.
Randomised, placebo-controlled trial on topiramate add-on therapy for weight reduction and symptomatology in overweight/obese persons with Schizophrenia
(Elsevier Ltd, 2022) Chandradasa, M.; Ruwanpriya, S.; de Silva, S.; Rathnayake, L.; Kuruppuarachchi, K.A.L.A.
Introduction: Higher cardiovascular mortality is seen with schizophrenia due to the disorder itself and antipsychotic use. South Asians are more vulnerable to developing metabolic disorders than others. Resource-limited settings in South Asia have only a few mental health professionals, and individualised case management is mostly unavailable. Therefore, there is less monitoring and personalised support for diet and physical exercise programmes. Topiramate is useful for weight reduction and improvement of psychopathology in schizophrenia. However, there has been only one previous randomised controlled trial (RCT) done in South Asia, which possesses a quarter of the world's population. Methods: We conducted a double-blind RCT in an outpatient setting in Sri Lanka. We compared topiramate 100 mg/day with a placebo in overweight/obese adults with schizophrenia who have been on antipsychotics for at least a year. We obtained monthly anthropometric measurements and assessed the symptomatology using the brief psychiatric rating scale (BPRS). Results: Fifty patients each in the topiramate and placebo arms completed the study. Topiramate add-on therapy led to significant weight/Body Mass Index reduction and improved symptomatology as measured by the BPRS compared to the placebo. The topiramate group had significantly more reporting of loss of appetite. Discussion: According to available data, this is the RCT with most participants assessing the use of topiramate in schizophrenia and only the second in South Asia. Topiramate was shown to be useful for weight reduction and symptomatic improvement in persons with schizophrenia in a resource-limited setting in South Asia.
Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial.
(The Lancet. Diabetes & Endocrinology., 2019) Ray, K.K.; Colhoun, H.M.; Szarek, M.; Baccara-Dinet, M.; Bhatt, D.L.; Bittner, V.A.; Budaj, A.J.; Diaz, R.; Goodman, S.G.; Hanotin, C.; Harrington, R.A.; Jukema, J.W.; Loizeau, V.; Lopes, R.D.; Moryusef, A.; Murin, J.; Pordy, R.; Ristic, A.D.; Roe, M.T.; Tuñón, J.; White, H.D.; Zeiher, A.M.; Schwartz, G.G.; Steg, P.G.; de Silva, H.A.ODYSSEY OUTCOMES Committees and Investigators.
BACKGROUND: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4-1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. METHODS: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65-1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. FINDINGS: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20-2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25-2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78-2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65-2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, -0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89-1·11). HRs were 0·97 (95% CI 0·87-1·09) for patients with prediabetes and 1·30 (95% CI 0·93-1·81) for those with normoglycaemia (pinteraction=0·11). INTERPRETATION: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65-1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes.
Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial
(Public Library of Science, 2011) de Silva, H.A.; Pathmeswaran, A.; Ranasinha, C.D.; Jayamanne, S.; Samarakoon, S.B.; Hittarage, A.; Kalupahana, R.; Ratnatilaka, G.A.; Uluwatthage, W.; Aronson, J.K.; Armitage, J.M.; Lalloo, D.G.; de Silva, H.J.
BACKGROUND: Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial. METHODS AND FINDINGS: In total, 1,007 patients were randomized, using a 2 × 2 × 2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25-67) at 1 h and by 38% (95% CI 26-49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. CONCLUSIONS: Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized.
Comparison of one week and two weeks of triple therapy for the eradication of Helicobacter pylori in a Sri Lankan population: a randomised, controlled study
(Sri Lanka Medical Association, 2004) de Silva, H.A.; Hewavisenthi, J.; Pathmeswaran, A.; Dassanayake, A.S.; Navarathne, N.M.M.; Peiris, R.; de Silva, H.J.
INTRODUCTION: Resistance of Helicobacter pylori to antibiotics may be particularly high in parts of the tropics. Infection may prove difficult to eradicate in such situations, and there is some evidence of benefit in increasing the duration of treatment (triple therapy) from 1 week to 2 or 3 weeks. AIM: To assess the efficacy and tolerability of 1 week versus 2 weeks of triple therapy for eradication of H. pylori in a Sri Lankan population. METHODS: Eighty two patients aged 18-70 years with gastritis or peptic ulcer and testing positive for H. pylori infection were randomly allocated totwo treatment groups. Both groups received omeprazole 20 mg, clarithromycin 250 mg, and tinidazole 500 mg. Group A (n = 42) received the trial medication twice daily for 1 week and the Group B (n = 40) twice daily for 2 weeks. H. pylori eradication was defined as a negative 14C labelled urea breath test at 2 weeks after completion of the therapy. RESULTS: H. pylori infection was eradicated in 36 (85.7%) patients in Group A and 36 (90%) patients in Group B (p = 0.9). Twenty three (55%) patients in Group A and 17 (43%) in Group B reported adverse effects attributable to trial medication (p = 0.387); none were serious. Three (7.5%) patients in Group B discontinued treatment due to adverse events that developed on days 7, 9 and 10. CONCLUSION: Twice daily treatment with clarithromycin, tinidazole, and omeprazole for 1 week is well tolerated and provides as good a rate of H.pylori eradication as 2-week therapy in Sri Lankan patients.
Liv. 52 in alcoholic liver disease: a prospective controlled trial
(Elsevier, 2003) de Silva, H.A.; Saparamadu, P.A.M.; Thabrew, M.I.; Pathmeswaran, A.; Fonseka, M.M.D.; de Silva, H.J.
Liv.52, a hepatoprotective agent of herbal origin, is used empirically for the treatment of alcoholic liver disease in Sri Lanka. We conducted acontrolled trial to assess the efficacy of Liv.52 in patients with alcoholic liver disease. Patients with evidence of alcoholic liver disease attending outpatient clinics were included in a prospective, double blind, randomized, placebo controlled trial. During the trial period, 80 patients who fulfilled inclusion criteria were randomly assigned Liv.52 (cases; n = 40) or placebo (controls) the recommended dose of three capsules twice daily for 6 months. All patients underwent clinical examination (for which a clinical score was computed), and laboratory investigations for routine blood chemistry and liver function before commencement of therapy (baseline). Thereafter, clinical assessments were done monthly for 6 months, while laboratory investigations were done after 1 and 6 months of therapy. There was no significant difference in the age composition, alcohol intake and baseline liver function between the two groups. The two-sample t-test was used to analyze data obtained after 1 and 6 months of therapy against baseline values. There was no significant difference in clinical outcome and liver chemistry between the two groups at any time point. There were no reports of adverse effects attributable to the drug. Our results suggest that Liv.52 may not be useful in the management of patients with alcohol induced liver disease.
Multiple-dose activated charcoal for treatment of yellow oleander poisoning : a single-blind randomized placebo controlled trial
(Lancet Publishing Group, 2003) de Silva, H.A.; Fonseka, M.M.D.; Pathmeswaran, A.; Alahakoon, D.G.S.; Ratnatilaka, G.A.; Gunatilake, S.B.; Ranasinha, C.D.; Lalloo, D.G.; Aronson, J.K.; de Silva, H.J.
BACKGROUND: Deliberate self-poisoning with yellow oleander seeds is common in Sri Lanka and is associated with severe cardiac toxicity and a mortality rate of about 10%. Specialised treatment with antidigoxin Fab fragments and temporary cardiac pacing is expensive and not widely available. Multiple-dose activated charcoal binds cardiac glycosides in the gut lumen and promotes their elimination. We aimed to assess the efficacy of multiple-dose activated charcoal in the treatment of patients with yellow-oleander poisoning. METHODS: On admission, participants received one dose of activated charcoal and were then randomly assigned either 50 g of activated charcoal every 6 h for 3 days or sterile water as placebo. A standard treatment protocol was used in all patients. We monitored cardiac rhythm and did 12-lead electocardiographs as needed. Death was the primary endpoint, and secondary endpoints were life-threatening cardiac arrhythmias, dose of atropine used, need for cardiac pacing, admission to intensive care, and number of days in hospital. Analysis was by intention to treat. FINDINGS: 201 patients received multiple-dose activated charcoal and 200 placebo. There were fewer deaths in the treatment group (five [2.5%] vs 16 [8%]; percentage difference 5.5%; 95% CI 0.6-10.3; p=0.025), and we noted difference in favour of the treatment group for all secondary endpoints, apart from number of days in hospital. The drug was safe and well tolerated. INTERPRETATION: Multiple-dose activated charcoal is effective in reducing deaths and life-threatening cardiac arrhythmias after yellow oleander poisoning and should be considered in all patients. Use of activated charcoal could reduce the cost of treatment.
Red blood cell antioxidant levels in Wuchereria bancrofti infections
(Academic Press, 2002) Premaratna, R.; Chandrasena, T.G.A.N.; Abeyewickreme, W.; Chandrasena, L.G.; Senerath, S.; de Silva, N.R.; de Silva, H.J.
The elimination of microfilariae of Wuchereria bancrofti is probably mediated by free radicals. Red cell catalase (C), glutathione peroxidase (GPX), and superoxide dismutase (SOD) activity levels were measured as an indirect method of assessing blood oxidant status in 29 asymptomatic microfilaraemics, 29 "endemic normals", and 29 controls living in a non-endemic area. Changes in the activity of these enzymes were also compared over a one month period in 22 asymptomatic microfilaraemics randomised to receive either single dose or 14 day treatment with diethyl carbamazine citrate (DEC). Red cell GPX activity levels were significantly higher in "endemic normals" when compared to mf positive cases and non-endemic controls. An early and significant increase in GPX activity (on days 3, 7 and 14 compared to pretreatment levels, p<0.01) was observed after DEC in both treatment groups. Increases in the activity of catalase and SOD became significant only on days 14 and 30 respectively. The percentage reduction in microfilaraemia correlated significantly with the percentage increase in GPX activity levels (R(2)=0.58, p=0.6 x 10(-5)). Our results may suggest a role for GPX related oxidant species in the elimination of microfilariae.
Effect of carbohydrates meals for varying consistency on gastric myoelectrical activity
(Singapore Medical Association, 2002) Ferdinandis, T.G.H.C.; Dissanayake, A.S.; de Silva, H.J.
BACKGROUND: There is at present no agreement on the type of test meal to be used when performing EGG. To our knowledge the response of thestomach to high carbohydrate isocaloric meals of different consistencies has not been formally assessed. AIM: To study 1) the effects of high carbohydrate meals of varying consistency on EGG activity; and 2) the effects of increasing the calorie content of a meal without changing its consistency and composition on the postprandial EGG. SUBJECTS: Eighteen healthy volunteers, six males (age: 21-35 year, weight: 45-60 kg) and 12 females in the follicular phase of the menstrual cycle (age: 24-30 years, weight: 45-55 kg). METHODS: Following an overnight fast subjects were given three high carbohydrate, low fat, isocaloric meals (165-170 kcal) of different consistencies (solid, semisolid, liquid), on three separate days in a random order. The liquid and semisolid meals were equal in volume (200 ml) while the volume of the solid meal was smaller. One hour EGG recordings were done in the fasting and fed states in each subject. As a second step, ten of the above volunteers (taken randomly) were given the solid test meal on a separate day after increasing the calorie content of the meal to 350 kcal. RESULTS: The power of the EGG at the dominant frequency significantly increased after solid (175 kcal meal: fasting 49 +/- 12 dB vs. fed 57 +/- 13 dB; p < 0.05, 375 kcal meal: fasting 48.5 +/- 12.9 dB vs fed 58.1 +/- 11.7 dB) and semisolid (fasting 50 +/- 12 dB vs. fed 55 +/- 13; P < 0.05). The increase in power was not significantly different when fed with solids and semisolids. There was no statistically significant change in EGG power during the first 15 or 60 minutes after the liquid meal. Feeding showed no significant effect on the dominant frequency and the percentage of 2-4 cpm waves of the EGG with any of the three types of test meals. CONCLUSIONS: Solid and semisolid meals high in carbohydrate and low in fat are capable of inducing a significant increase in the EGG power in normal subjects. Isocaloric solid and semisolid meals have similar effects on gastric slow wave activity. EGG appears unaffected by the liquid meal. Therefore only an increase in the power of the EGG can be regarded as normal if a high carbohydrate solid or a semisolid meal is given as the test meal when performing an EGG.
Do women with pre-eclampsia and their babies benifit from management sulphate? The Magpie Trial: a randomised placebo controlled trial
(Lancet Publishing Group, 2002) Altman, D.; Carroli, G.; Duley, L.; Farrell, B.; Moodley, J.; Neilson, J.; Smith, D.; Fernando, S. with Magpie Trial Collaborative Group

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