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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16 years: A Randomised, placebo-controlled, phase 3 trial(J. Onwhyn, 2020) Biswal, S.; Borja-Tabora, C.; Martinez Vargas, L.; Velásquez, H.; Theresa Alera, M.; Sierra, V.; Johana Rodriguez-Arenales, E.; Yu, D.; Wickramasinghe, V.P.; Duarte Moreira, E. Jr.; Fernando, A. D.; Gunasekera, D.; Kosalaraksa, P.; Espinoza, F.; López-Medina, E.; Bravo, L.; Tuboi, S.; Hutagalung, Y.; Garbes, P.; Escudero, I.; Rauscher, M.; Bizjajeva, S.; LeFevre, I.; Borkowski, A.; Saez-Llorens, X.; Wallace, D.; TIDES study groupBACKGROUND: A substantial unmet need remains for safe and effective vaccines against dengue virus disease, particularly for individuals who are dengue-naive and those younger than 9 years. We aimed to assess the efficacy, safety, and immunogenicity of a live attenuated tetravalent dengue vaccine (TAK-003) in healthy children aged 4-16 years. METHODS: We present data up to 18 months post-vaccination from an ongoing phase 3, randomised, double-blind trial of TAK-003 in endemic regions of Asia and Latin America (26 medical and research centres across Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). Healthy children aged 4-16 years were randomly assigned 2:1 (stratified by age and region) to receive two doses of TAK-003 or two doses of placebo, 3 months apart. Investigators, participants and their parents or guardians, and sponsor representatives advising on trial conduct were masked to trial group assignments. Participants presenting with febrile illness were tested for virologically confirmed dengue (VCD) by serotype-specific RT-PCR. In timeframes beginning 30 days post-second dose, the primary endpoint (overall vaccine efficacy) was assessed in the first 11 months, and the secondary endpoints (efficacy by baseline serostatus, serotype, hospitalised dengue, and severe dengue) in the first 17 months. This study is registered with ClinicalTrials.gov, NCT02747927. FINDINGS: 20 099 participants were randomly assigned and vaccinated between Sept 7, 2016, and Aug 18, 2017; 19 021 (94·6%) were included in the per protocol analysis, and 20 071 (99·9%) in the safety set. The primary endpoint was achieved with an overall vaccine efficacy of 80·2% (95% CI 73·3 to 85·3; 61 cases of VCD in the TAK-003 group vs 149 cases of VCD in the placebo group). In the secondary endpoint assessment timeframe, an overall vaccine efficacy of 73·3% (95% CI 66·5 to 78·8) was observed. Analysis of secondary endpoints showed efficacies of 76·1% (95% CI 68·5 to 81·9) in individuals who were seropositive at baseline, 66·2% (49·1 to 77·5) in individuals who were seronegative at baseline, 90·4% (82·6 to 94·7) against hospitalised dengue, and 85·9% (31·9 to 97·1) against dengue haemorrhagic fever. Efficacy varied by individual serotypes (DENV 1, 69·8% [95% CI 54·8 to 79·9]; DENV 2, 95·1% [89·9 to 97·6]; DENV 3, 48·9% [27·2 to 64·1]; DENV 4, 51·0% [-69·4 to 85·8]). Cumulative rates of serious adverse events were similar in TAK-003 (4·0%) and placebo (4·8%) recipients, and were consistent with expected medical disorders in the study population. Infection was the most frequent reason leading to serious adverse events. 20 participants (<0·1% of the safety set) were withdrawn from the trial due to 21 adverse events by the end of part two; 14 of these participants received TAK-003 and six received placebo. INTERPRITATION: TAK-003 was well tolerated and efficacious against symptomatic dengue in children regardless of serostatus before immunisation. Vaccine efficacy varied by serotype, warranting continued follow-up to assess longer-term vaccine performance. FUNDING: Takeda Vaccines.Item Correlates of serum homocysteine in a Sri Lankan population(American Association For Clinical Chemistry, 2010) Chackrewarthy, S.; Wijayasinghe, Y.S.; Gunasekera, D.; Wickremasinghe, R.; Kato, N.Correlates of total serum homocysteine concentration in a Sri Lankan population BACKGROUND: Hyperhomocysteinemia, a possible risk factor for vascular disease occurs at a higher prevalence in South Asian countries. Serum homocysteine concentrations are influenced by genetic, nutritional and lifestyle factors. Correlates of total serum homocysteine concentration (tHcy) are not well characterized in the Sri Lankan population. Such information is important in developing therapeutic and preventative strategies. OBJECTIVE: To investigate the factors potentially associated with fasting levels of serum tHcy in a Sri Lankan population. METHODS: In a cross sectional study, 177 apparently healthy volunteers (91 men and 86 women) aged 38-65 years were selected from residents in an urban health administrative area. Individuals with a history of chronic disease and with any pharmacological treatment were excluded from the study. Information on diet, lifestyle factors and medical history were recorded. Anthropometric indices and blood pressure were measured according standard protocols. Fasting serum levels of tHcy, insulin, creatinine, folate and lipids were estimated using standard protocols. RESULTS: Fasting serum tHcy levels were higher in males than in females (geometric mean +/- SD, 13.75 mumol/l +/- 1.41 Vs. 9.58 mumol/l +/- 1.43, p<0.001) and were positively associated with age (r=0.204, p< 0.01) in both sexes. 32.3% of males and 10.3% of females had mild hyperhomocysteinemia (tHcy>15mumol/l). tHcy levels were significantly higher in smokers than in non-smokers (geometric mean +/- SD, 14.58 mumol/l +/- 1.44 Vs.12.71 mumol/l +/- 1.37, p<0.05) and in alcohol consumers than in non-consumers (geometric mean +/- SD, 14.53 mumol/l +/- 1.43 Vs.12.14 mumol/l +/- 1.32, p< 0.02). In males, tHcy levels were negatively related to serum insulin (r= -0.397, p<0.001) and BMI (r= -0.244, p <0.02) and positively related to serum creatinine (r=0.235, p<0.02). In females, there was a positive relationship between tHcy and systolic blood pressure (r= 0.239, p<0.02) but there was no significant correlation with serum insulin. In both sexes, serum tHcy levels strongly correlated with serum folate (r= -0.412, p<0.001). There were no significant associations between tHcy and serum lipids. Stepwise regression analysis confirmed the associations between tHcy and folate (p<0.001 in both sexes), insulin (p=0.026 in males) and creatinine (p=0.036 in males). CONCLUSION: Low intake of folate, alcohol consumption and smoking were associated with increased tHcy concentrations. Serum insulin and creatinine were independent correlates of tHcy in males, but not in females. Difference in tHcy levels between sexes may partly be attributed to differences in lean muscle mass and to a metabolic link between creatinine synthesis and homocysteine production. Insulin may regulate serum tHcy concentrations by homocysteine remethylation or by increasing homocysteine clearance.Item Effect of mebendazole threapy in pregnancy on birth outcome(Sri Lanka Medical Association, 1998) de Silva, N.; Sirisena, J.; Gunasekera, D.; de Silva, J.OBJECTIVES : A prospective, unmatched, case-control study was done to assess the safety of mebendazole threapy in pregnancy, a hitherto uninvestigated factor. DESIGN : All women delivering in the University Obstetrics Unit of the Ragama Teaching Hospital between May 1996 and, March 1997 were administered a questionnaire soon after delivery. Details of the birth and the baby were recorded; suspected defects were confirmed by a paediatrician. The incidence of congenital defects in babies of mothers who had taken mebendazole during the pregnancy was compared with the incidence among those who had not taken an anthelmintic (controls). Data analysis was done using Epi Info 6.03. RESULTS : Of 3688 women, 73.5% had taken mebendazole, 24.8% had not taken any any anthelmintic , 1.1% had taken an anthelmintic but could not identify it and 0.6% had taken pyrantel or albedazole. The incidence of birth defects was 2.36% {64/2711) in the mebendazole group compared with 2.3% (21/913) in the controls (odds ratio 1.03, 95% confidence limits 0.61 - 1.75). This difference was not statistically significant even when corrected for other known risk factors by stratified analysis . Data regarding timing of mebendazole threapy was available for 2660 women; 6.9% in the first trimester, 83.8% in the second, and 9.2% in the third. The incidence of birth defects among women who had taken mebendazole in the first trimester was 3.24% (6/185). giving an odds ratio of 1.42 against the controls; this was also not statistically significant.CONCLUSIONS : The use of mebendazole in pregnancy does not lead to a significant increase in the risk of congenital defects.