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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Incidence and risk factors for metabolic syndrome among urban, adult Sri Lankans: a prospective, 7-year community cohort, follow-up study.(BioMed Central, 2019) de Silva, S.T.; Niriella, M.A.; Ediriweera, D.S.; Kottahachchi, D.; Kasturiratne, A.; de Silva, A.P.; Dassanayake, A.S.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.BACKGROUND:The metabolic syndrome (MetS) is a clustering of abdominal obesity, diabetes and prediabetes, high cholesterol and high blood pressure, that confers an increased risk of cardiovascular disease. There is limited data on incidence of MetS from South Asia. This study investigated incidence and risk factors for new onset MetS in an urban adult Sri Lankan population.METHODS:Subjects (selected by age-stratified random sampling from the Ragama Medical Officer of Health area) were screened initially in 2007 (35-64 years) and re-evaluated in 2014 (42-71 years). On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, and biochemical/serological tests. MetS was diagnosed on International Diabetes Federation (IDF-2006) criteria. Total body fat (TBF) and visceral fat percentage (VFP) were measured in 2014, using body impedance method. Incidence and factors at baseline, associated with new onset MetS, were investigated among those who presented for re-evaluation.RESULTS:2985 (99.1%) [1636 (54.8%) women (54.8%); median age (IQR) 53 (47-59) years] from the initial cohort in 2007 had complete data. 2148 (71.9%) [1237 (57.6%) women; median age (IQR) 60 (54-66) years] attended follow-up. 949 of them [701 (73.9%) women; median age (IQR) 60 (54-65) years] had MetS (prevalence 47.2%, 95% CI 45.0-49.4%). Of 1246 who did not have MetS in 2007, 265 [178 (67.1%) women, median age (IQR) 57 (51-64) years] had developed MetS after 7 years (annual incidence 3.5% (95% CI 2.4-4.5%). Females (OR = 4.9, 95% CI 3.4-7.4), BMI > 23 kg/m2 in 2007 (OR = 1.6 per unit increase, 95% CI 1.5-1.7), weight gain (by 2-5% OR = 2.0, 95% CI 1.1-3.5; by > 5% OR = 2.2, 95% CI 1.4-3.4), and increase in waist circumference (by 2-5% OR = 7.0, 95% CI 4.0-12.2; by > 5% OR = 13.4, 95% CI 8.3-22.4) from baseline and presence of non-alcoholic fatty liver disease (NAFLD) in 2007 (OR = 1.70, 95% CI 1.04-2.76) were associated new onset MetS. Those with MetS had abnormal VFP and TBF in 2014 [P < 0.001].CONCLUSION:In this study, annual incidence of MetS was 3.5%. Female gender, BMI > 23 kg/m2 and NAFLD in 2007 and increase in weight and waist circumference from baseline were significantly associated with new onset MetS. Obesity was the best predictor of future MetSItem Multicomponent intervention versus usual care for management of hypertension in rural Bangladesh, Pakistan and Sri Lanka: study protocol for a cluster randomized controlled trial(BioMed Central, 2017) Jafar, T.H.; Jehan, I.; de Silva, H.A.; Naheed, A.; Gandhi, M.; Assam, P.; Finkelstein, E.A.; Quigley, H.L.; Bilger, M.; Khan, A.H.; Clemens, J.D.; Ebrahim, S.; Turner, E.L.; Kasturiratne, A.; for COBRA-BPS Study GroupBACKGROUND: High blood pressure (BP) is the leading attributable risk for cardiovascular disease (CVD). In rural South Asia, hypertension continues to be a significant public health issue with sub-optimal BP control rates. The goal of the trial is to compare a multicomponent intervention (MCI) to usual care to evaluate the effectiveness and cost-effectiveness of the MCI for lowering BP among adults with hypertension in rural communities in Bangladesh, Pakistan and Sri Lanka. METHODS/DESIGN: This study is a stratified, cluster randomized controlled trial with a qualitative component for evaluation of processes and stakeholder feedback. The MCI has five components: (1) home health education by government community health workers (CHWs), (2) BP monitoring and stepped-up referral to a trained general practitioner using a checklist, (3) training public and private providers in management of hypertension and using a checklist, (4) designating hypertension triage counter and hypertension care coordinators in government clinics and (5) a financing model to compensate for additional health services and provide subsidies to low income individuals with poorly controlled hypertension. Usual care will comprise existing services in the community without any additional training. The trial will be conducted on 2550 individuals aged ≥40 years with hypertension (with systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, based on the mean of the last two of three measurements from two separate days, or on antihypertensive therapy) in 30 rural communities in Bangladesh, Pakistan and Sri Lanka. The primary outcome is change in systolic BP from baseline to follow-up at 24 months post-randomization. The incremental cost of MCI per CVD disability-adjusted life years averted will be computed. Stakeholders including policy makers, provincial- and district-level coordinators of relevant programmes, physicians, CHWs, key community leaders, hypertensive individuals and family members in the identified clusters will be interviewed. DISCUSSION: The study will provide evidence of the effectiveness and cost-effectiveness of MCI strategies for BP control compared to usual care in the rural public health infrastructure in South Asian countries. If shown to be successful, MCI may be a long-term sustainable strategy for tackling the rising rates of CVD in low resourced countries.Item Incidence and risk factors for Non-Alcoholic Fatty Liver Disease in an urban, adult Sri Lankan population – a community cohort follow-up study(Sage Publishing, 2015) Niriella, M.; Kasturiratne, A.; de Silva, S.; Perera, R.; Subasinghe, C.; Kodisinghe, K.; Priyantha, C.; Rishikeshavan, V.; Dassanayake, A.; de Silva, A.; Pathmeswaran, A.; Kato, N.; de Silva, H.J.INTRODUCTION: We previously reported a community prevalence of 33% for NAFLD in an urban, adult Sri Lankan population. We also found a significant association between patatin-like phospholipase domain containing 3 (PNPLA3) gene rs738409 polymorphism, and susceptibility to NAFLD in the same population, after testing 10 selected single nucleotide polymorphisms (SNPs) in a case control study. AIMS & METHODS: The aim of this study was to assess the incidence and risk factors for NAFLD in this population after seven years of follow-up. The study population consisted of 42-71-year-old adults, originally selected by age stratified random sampling from electoral lists from Ragama, Sri Lanka. The target population was screened initially in 2007 and subsequently invited back for re-evaluation in 2014. On both occasions they were assessed using a structured interview, clinical and anthropometric measurements, liver ultrasound, and biochemical and serological tests. NAFLD was diagnosed on established ultrasound criteria for fatty liver (two out of three criteria: increased echogenecity of the liver compared to kidney and spleen, obliteration of the vascular architecture of the liver and deep attenuation of the ultrasonic signal), safe alcohol consumption (Asian standards: 514 units/week for men, 57 units/week for females) and absence of hepatitis B and C markers. Non-NAFLD controls were defined as subjects who did not have any of the ultrasound criteria for NAFLD. We also performed an updated case-control study to investigate associations of selected genetic variants with incident NAFLD [SNPs: PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B (rs4240624) and NCAN (rs2228603), APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870) and STAT3 (rs6503695 and rs9891119)]. RESULTS: Of the 2985 original study participants, 2155 (72.2%) (1244 women and 911 men; mean age 59.2 years [SD, 7.7]) participated in the follow-up assessment. 1322 [mean age 58.9 years (SD, 7.6), 483 (53.0%) men and 839 (67.4%) women] had NAFLD. Out of 795 [466 (58.6%) women] participants who did not have NAFLD in the original study, 365 [226 (61.9%) women, mean age 58.6 years (SD, 7.9)] had developed NAFLD after 7 years, giving an annual incidence rate 6.6%. On multivariate analysis, increased waist circumference [OR 1.96(1.30 – 2.97), p=0.001], BMI4 23 kg/m2 [OR 2.93(1.99 – 4.30), p50.001] and raised plasma triglycerides (TG) [OR 1.49(1.03 – 2.13), p=0.03] were independently predictive of incident NAFLD in this cohort, while raised BP and reduced HDL, were not. In the updated association study involving 1310 cases and 427 controls, we found borderline association with NAFLD at two of the 10 candidate loci: rs4240624 at PPP1R3B and rs738409 at PNPLA3 (one-tailed P=0.044 and 0.033, respectively). CONCLUSION: In this community cohort follow-up study in an urban, adult population in Sri Lanka, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of the metabolic syndrome, and showed tendency of association at PNPLA3 and PPP1R3B gene polymorphisms. Disclosure of Interest: None declaredItem Genetic variants of NAFLD in an urban Sri Lankan community(Wiley Blackwell Scientific Publications, 2013) Niriella, M.A.; Kasturiratne, A.; Akiyama, K.; Takeuchi, F.; Isono, M.; Dassanayake, A.S.; de Silva, A.P.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.OBJECTIVE: Recently, genome-wide association studies (GWAS) have successfully identified loci associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in populations of European descent. No large-scale genetic studies have been performed thus far in South Asian populations. Therefore, as part of a community-based cohort study in an urban adult population of Sri Lankans, we investigated associations of genetic variants with NAFLD, diagnosed on established ultrasound criteria, and its related phenotypes. METHODS: We selected 10 single nucleotide polymorphisms (SNPs), all previously reported to be associated with NAFLD in populations of European and/or South Asian ancestry, for a case-control replication study. They included loci derived from GWAS [PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B (rs4240624) and NCAN (rs2228603)] plus those from candidate gene studies [APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870) and STAT3 (rs6503695 and rs9891119)]. Genotype data of 2988 participants were used for the analysis. RESULTS: A significant NAFLD association was observed for PNPLA3 (rs738409) [OR = 1.25, 95% CI 1.08–1.44, P = 0.003)]; rs738409 was also associated with a trend towards lower serum triglycerides APOC3 variants were significantly (P = 7.3–7.5 × 10–8) associated with higher triglycerides, but not with NAFLD (OR = 0.86). Apart from SNP–lipid associations previously reported at the GCKR, PPP1R3B and NCAN loci, there were no other prominent associations. CONCLUSION: Our data confirm that the PNPLA3 gene variant is significantly associated with NAFLD in the general Sri Lankan population but could not replicate previously reported disease associations at other loci, reinforcing the importance of further large-scale study on genetic variants in diverse populations to better understand the pathophysiology of NAFLD.Item Prevalence of Chronic Kidney Disease among older adults in urban Sri Lanka - Tip of the iceburg?(The International Society of Nephrology, 2015) de Silva, S.T.; Kasturiratne, A.; Chackrewarthy, S.INTRODUCTION: Prevalence of chronic kidney disease (CKD) is increasing worldwide, mainly due to increasing diabetes mellitus (DM) and hypertension (HPT) in aging populations. Although these diseases affect many, data on population prevalence of CKD in Sri Lanka is scarce. However, a CKD of uncertain aetiology (CKDu), mainly seen in the North Central parts of the country, receives much attention. The prevalence of CKDu among adults in the affected areas was estimated to be 15.3% in 2012. Our objectives were to identify the prevalence of CKD in an urban adult Sri Lankan population and compare that to the prevalence of CKDu. METHODS: Subjects were randomly selected from the Ragama Health Study (RHS), an on-going community based research project of the Ragama Medical Officer of Health area with 3012 adult participants. Data was obtained using an interviewer-administered questionnaire. Serum creatinine was tested and estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. CKD was defined as eGFR <60 ml/min/1.73m2, using the KDIGO/KDOQI classifications. RESULTS: Of 301 participants with a mean age of 57.5 years (range 40-73 years), 178/301 (59.1%) were female. 43/301 had eGFR <60 ml/min/1.73m2, giving a CKD prevalence of 14.3% in our sample. 34/43 (79.1%) were in CKD Stage IIIA. 5/43 (11.6%) had only DM, 14/43 (32.6%) had only HPT and 13/43 (30.2%) had both DM and HPT, as probable aetiological factors for CKD. A cause of CKD could not be readily identified in 11/43 (25.6%). Patients with CKD were significantly older than 60 years (p<0.000), and were more likely to have DM (p<0.012), HPT (p<0.000), coronary artery disease (p<0.031) and hyperlipidemia (p<0.0230), compared to those without CKD. CONCLUSIONS: CKD prevalence in our sample was similar to the prevalence of CKDu in North Central Sri Lanka. As expected, DM and HPT were the primary associated co-morbidities. Most CKD patients were in stage IIIA, where early recognition and better control of co-morbidities are known to retard progression. CKD of known aetiology is under-recognized in Sri Lanka, and is probably as significant a problem as CKDu. Large population-based studies are needed to better understand the actual size of the problem.Item Prevalence of non-alcoholic fatty liver disease and its risk factors in an urban adolescent cohort in Sri Lanka(Sri Lanka Medical Association, 2015) Jayasinghe, Y.C.; Rajindrajith, S.; Kasturiratne, A.; de Silva, S.T.; Niriella, M.A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Priyantha, T.A.C.L.; Vithiya, K.; Pathmeswaran, A.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: High prevalence of non-alcoholic fatty liver disease (NAFLD) is reported among adults in Sri Lanka. Although limited data on childhood obesity is available, community prevalence of NAFLD and its risk factors among adolescents is unknown. We investigated the prevalence and risk factors for NAFLD in an urban adolescent birth cohort in Sri Lanka. METHODS: The study population consisted 14 year-olds, belonging to the birth cohort born in 2000, residing in the Ragama Medical Officer of Health area. NAFLD was diagnosed based on established ultrasound criteria. Anthropometric measurements, blood pressure (BP) and total body fat distribution (TBF) estimates were made. Fasting blood sugar, serum insulin, fasting serum lipid and serum alanine aminotransferase (ALT) levels were measured. Independent predictors of NAFLD were determined by multivariate analysis. RESULTS: 508 adolescents [263 (51.8%) girls] participated in the study. Overall 44 (8.7%) had NAFLD [22 (8.4%) girls]. 46 (18.8%) boys and 54 (20.5%) girls had a BMI above the equivalent of 23 kgm2in adults. 44 (17.1%) boys and 77 (29.3%) girls had elevated TBF. On multivariate analysis, having an elevated BMI [OR=10.1 (95% confidence interval: 3.9-29.2) and elevated TBF [OR=4.4 (95% confidence interval: 1.5-12.8)] were independently associated with NAFLD. CONCLUSION: The prevalence of NAFLD among adolescents in this urban Sri Lankan community is high, and is strongly associated with obesity and abnormal TBF. Despite elevated TBF being commoner in girls, we found no gender differences in prevalence of NAFLD among adolescents in this urban Sri Lankan community is strongly associated with obesity and abnormal TBF. Our findings emphasize the needs to access these risk factors through preventive and screening programs.