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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Hydroxychloroquine for post-exposure prophylaxis of COVID-19 among naval personnel in Sri Lanka: study protocol for a randomized, controlled trial(BioMed Central, 2020) Niriella, M.A.; Ediriweera, D.S.; de Silva, A.P.; Premaratna, R.; Balasooriya, P.; Duminda, K.D.; Malavige, N.G.; Wanigasuriya, K.; Lekamwasam, S.; Kularathne, S.A.; Siribaddana, S.; de Silva, H.J.; Jayasinghe, S.BACKGROUND: The first case of a coronavirus 2019 (COVID-19) infection in a Sri Lankan was reported on March 11, 2020. The situation in Sri Lanka changed with the rapid increase of personnel contracting COVID-19 in a naval base camp that housed more than 4000 people. This provided a unique opportunity to study the effectiveness of hydroxychloroquine (HCQ) for post-exposure prophylaxis (PEP), while taking stringent, non-pharmacologic, public health measures to prevent spread. Our aim is to study the effectiveness and safety of HCQ for PEP among naval personnel with exposure to COVID-19-positive patients. METHODS/DESIGN: This is a placebo-controlled, randomized, clinical trial carried out in the naval base camp and quarantine centers of the Sri Lanka Navy, Ministry of Defense, Sri Lanka. Navy personnel who are exposed to a patient with confirmed COVID-19 infection but test negative for the virus on reverse real-time polymerase chain reaction (rRT-PCR) at recruitment will be randomized, 200 to each arm, to receive HCQ or placebo and monitored for the development of symptoms or rRT-PCR positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus for 14 days. DISCUSSION: This trial will provide high-quality evidence of the effectiveness and safety of HCQ as PEP for COVID-19. The study design is unique due to the circumstances of the outbreak in a confined area among otherwise healthy adults, at a relatively early stage of its spread. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry (SLCTR) SLCTR/2020/011. Registered on 04 May 2020. KEYWORDS: COVID-19; HCQ; Hydroxychloroquine; Post-exposure; Prophylaxis; Randomized controlled trial; SARS-CoV-2; Sri Lanka.Item A Randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming(Wiley-Blackwell, 2017) Isbister, G.K.; Jayamanne, S.; Mohamed, F.; Dawson, A.H.; Maduwage, K.; Gawarammana, I.; Lalloo, D.G.; de Silva, H.J.; Scorgie, F.E.; Lincz, L.F.; Buckley, N.A.BACKGROUND: Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom induced consumption coagulopathy (VICC). OBJECTIVES: We investigated the effect of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. METHODS: We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1:1) high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4U FFP. The primary outcome was the proportion of patients with an international normalized ratio (INR)<2, 6h post-antivenom. Secondary outcomes included anaphylaxis, major haemorrhage, death and clotting factor recovery. RESULTS: From 214 eligible patients, 141 were randomized; 71 to high-dose antivenom, 70 to low-dose antivenom/FFP; five had no post-antivenom bloods. The groups were similar except for a delay of 1h in antivenom administration for FFP patients. 6h post-antivenom 23/69 (33%) patients allocated high-dose antivenom had an INR<2 compared with 28/67 (42%) allocated low-dose antivenom/FFP [absolute difference 8%;95%Confidence Interval:-8% to 25%]. 15 patients allocated FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion related acute lung injury. Three deaths occurred in low-dose/FFP patients including one intracranial haemorrhage. There was no difference in recovery rates of INR or fibrinogen, but more rapid initial recovery of factor V and X in FFP patients. CONCLUSION: FFP post-antivenom in Russell's viper bites didn't hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting low-dose antivenom is sufficient. This article is protected by copyright. All rights reserved.Item Comparison of one and two weeks of triple therapy for eradication of H. pylori: a randomized, controlled study in a tropical country(Wiley Blackwell Scientific Publications, 2004) de Silva, H.A.; Hewavisenthi, J.; Pathmeswaran, A.; Navarathne, N.M.M; Peiris, R.; Dassanayake, A.S.; de Silva, H.J.INTRODUCTION: Resistance of H. 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 duration of treatment (triple therapy) from one week to two or three weeks. AIM : To assess the efficacy and tolerability of one-week versus two weeks triple therapy for eradication of H. pylori in a Sri Lankan population. METHODS: 82 consecutive patients aged 18–70 years with peptic ulcer disease testing positive for H. pylori infection (histology and rapid urease test on gastric antral biopsies) were randomly allocated to two treatment groups. The baseline characteristics of the two groups were similar. Both groups received omeprazole 20mg, clarithromycin 250mg, and tinidazole 500mg. Group A (n = 42) received the trial medication twice daily for one week and the Group B (n = 40) twice daily for two weeks. H. pylori eradication was defined as a negative 14C labeled urea breath test at two weeks after completion of therapy. The assessors were blind to randomization and other patient information. RESULTS; All patients presented for follow up after completion of therapy. H. pylori infection was eradicated in 36 (85.7%) patients in group A and 36 (90%) patients in group B (p = 0.9; 95% CI: -19.1 to 10.8). 23 (55%) patients in group A and 17 (43%) in group B reported adverse effects attributable to trial medication (p = 0.387); none were serious. 3 (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 one-week is well tolerated and provides as good a rate of H. pylori eradication as two weeks therapy in Sri Lankan patients.Item A Randomized Controlled Trial of a brief Intervention for delayed psychological effects in snakebite victims(Public Library of Science, 2015) Wijesinghe, C.A.; Williams, S.S.; Kasturiratne, A.; Dolawaththa, N.; Wimalaratne, P.; Wijewickrema, B.; Jayamanne, S.F.; Isbister, G.K.; Dawson, A.H.; Lalloo, D.G.; de Silva, H.J.BACKGROUND: Snakebite results in delayed psychological morbidity and negative psycho-social impact. However, psychological support is rarely provided to victims. AIM: To assess the effectiveness of a brief intervention which can be provided by non-specialist doctors aimed at reducing psychological morbidity following snakebite envenoming. METHOD: In a single blind, randomized controlled trial, snakebite victims with systemic envenoming [n = 225, 168 males, mean age 42.1 (SD 12.4) years] were randomized into three arms. One arm received no intervention (n = 68, Group A), the second received psychological first aid and psychoeducation (dispelling prevalent cultural beliefs related to snakebite which promote development of a sick role) at discharge from hospital (n = 65, Group B), while the third received psychological first aid and psychoeducation at discharge and a second intervention one month later based on cognitive behavioural principles (n = 69, Group C). All patients were assessed six months after hospital discharge for the presence of psychological symptoms and level of functioning using standardized tools. RESULTS: At six months, there was a decreasing trend in the proportion of patients who were positive for psychiatric symptoms of depression and anxiety from Group A through Group B to Group C (Chi square test for trend = 7.901, p = 0.005). This was mainly due to a decreasing trend for symptoms of anxiety (chi-square for trend = 11.256, p = 0.001). There was also decreasing trend in the overall prevalence of disability from Group A through Group B to Group C (chi square for trend = 7.551, p = 0.006), predominantly in relation to disability in family life (p = 0.006) and social life (p = 0.005). However, there was no difference in the proportion of patients diagnosed with depression between the three groups (chi square for trend = 0.391, p = 0.532), and the intervention also had no effect on post-traumatic stress disorder. CONCLUSIONS: A brief psychological intervention, which included psychological first aid and psychoeducation plus cognitive behavioural therapy that can be provided by non-specialist doctors appeared to reduce psychiatric symptoms and disability after snakebite envenoming, but not depression or post-traumatic stress disorder. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry: SLCTR/2011/003.Item 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.Item 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.Item 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.Item 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.Item 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.Item 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.