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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Validation of the World Health Organization/ International Society of Hypertension (WHO/ISH) cardiovascular risk predictions in Sri Lankans based on findings from a prospective cohort study(Public Library of Science, 2021) Thulani, U.B.; Mettananda, K.C.D.; Warnakulasuriya, D.T.D.; Peiris, T.S.G.; Kasturiratne, K.T.A.A.; Ranawaka, U.K.; Chakrewarthy, S.; Dassanayake, A.S.; Kurukulasooriya, S.A.F.; Niriella, M.A.; de Silva, S.T.; Pathmeswaran, A.; Kato, N.; de Silva, H.J.; Wickremasinghe, A.R.INTRODUCTION AND OBJECTIVES: There are no cardiovascular (CV) risk prediction models for Sri Lankans. Different risk prediction models not validated for Sri Lankans are being used to predict CV risk of Sri Lankans. We validated the WHO/ISH (SEAR-B) risk prediction charts prospectively in a population-based cohort of Sri Lankans. METHOD: We selected 40-64 year-old participants from the Ragama Medical Officer of Health (MOH) area in 2007 by stratified random sampling and followed them up for 10 years. Ten-year risk predictions of a fatal/non-fatal cardiovascular event (CVE) in 2007 were calculated using WHO/ISH (SEAR-B) charts with and without cholesterol. The CVEs that occurred from 2007-2017 were ascertained. Risk predictions in 2007 were validated against observed CVEs in 2017. RESULTS: Of 2517 participants, the mean age was 53.7 year (SD: 6.7) and 1132 (45%) were males. Using WHO/ISH chart with cholesterol, the percentages of subjects with a 10-year CV risk <10%, 10-19%, 20%-29%, 30-39%, ≥40% were 80.7%, 9.9%, 3.8%, 2.5% and 3.1%, respectively. 142 non-fatal and 73 fatal CVEs were observed during follow-up. Among the cohort, 9.4% were predicted of having a CV risk ≥20% and 8.6% CVEs were observed in the risk category. CVEs were within the predictions of WHO/ISH charts with and without cholesterol in both high (≥20%) and low(<20%) risk males, but only in low(<20%) risk females. The predictions of WHO/ISH charts, with-and without-cholesterol were in agreement in 81% of subjects (ĸ = 0.429; p<0.001). CONCLUSIONS: WHO/ISH (SEAR B) risk prediction charts with-and without-cholesterol may be used in Sri Lanka. Risk charts are more predictive in males than in females and for lower-risk categories. The predictions when stratifying into 2 categories, low risk (<20%) and high risk (≥20%), are more appropriate in clinical practice.Item Patterns of alcohol use and occurrence of alcoholic fatty liver disease: a prospective, community cohort, 7-year follow-up study(Sri Lanka Medical Association, 2017) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyaratna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Data is limited on alcoholic fatty liver disease (AFLD). We investigated patterns of alcohol use and AFLD, among urban, adult, Sri Lankans. METHODS: Study population (selected by age-stratified random sampling from Ragama MOH-area) was screened initially in 2007 (35-64 years) and re-evaluated in 2014. On both occasions they were assessed by structured-interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. AFLD was diagnosed on ultrasound criteria, unsafe alcohol consumption (Asian standards: males>14units, females>7units per week) and absence of hepatitis B/C markers. Controls were individuals with unsafe alcohol consumption, but had no ultrasound criteria of AFLD. Case-control genetic-association for PNPLA3 (rs738409) polymorphism for AFLD was performed. RESULTS: A total of 2983/3012 (99%) had complete data. 272/2983(9.1%) were unsafe-drinkers [males- 70; mean-age 51.9 (SD-8.0) years]. 86/2983 (2.9%) of the cohort and 86/272 (31.6%) of unsafe-drinkers had AFLD [males-85; mean-age 50.2 (SD-8.6) years]. Males [p<0.001], increased waist circumference (WC) [p=0.001], BMI>23kg/m2 [p<0.001], raised triglycerides (TG) [p<0.001], low education level (LEL-not completed secondary-education) [p<0.01] and low monthly household-income (23kg/m2 [p<0.001], raised TG [p<0.001] and LEL [p<0.05] independently predicted incident-AFLD. The genetic association study [133-cases (combined 2007-2014), 97-controls] showed no association with AFLD at PNPLA3 (rs738409). CONCLUSION: The prevalence of AFLD was 2.9% in 2007 and annual incidence among heavy drinkers, after 7-year follow-up was 5.7%. Incident-AFLD was associated with males, obesity, raised TG and LEL.Item Incidence, prevalence and demographic and life style risk factors for obesity among urban, adult Sri Lankans: a community cohort follow-up study(Sri Lanka Medical Association, 2017) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Kottachchi, D.; Ranasinghe, R.M.A.G.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Obesity is a global problem. Data from the South Asian region is limited. METHODS: In a cohort follow-up study we investigated obesity among urban, adult, Sri Lankans (35-64y; selected by age-stratified random sampling from Ragama-MOH area; initial screening 2007; re-evaluation 2014). On both occasions structured interview, anthropometry, liver ultrasound, biochemical and serological tests were performed. Total body fat (TBF) and visceral fat percentage (VFP) were assessed by impedance in 2014. General-obesity (GO) was BMI>25kg/m2. Central-obesity (CO) was waist circumference (WC)>90cm males and WC>80cm females. Multinomial logistic regression was fitted to assess associations. RESULTS: In 2007 (n=2967), 614 (20.7%) were overweight [51.9%-women], 1161(39.1%) had GO [65.9%-women] and 1584(53.4%) had CO [71%-women]. Females (p<0.001), raised-TG (p<0.001), low-HDL (p<0.001), diabetes (p<0.001), hypertension (p<0.001), NAFLD (p<0.001), and low household income (p<0.001) were significantly associated with prevalent GO and CO respectively. Additionally, increased-age (p=0.05), low-educational level (p<0.001) and unhealthy eating (p<0.001) were associated with prevalent CO. Inadequate physical activity was not associated with either. 2137 (72%) attended follow-up in 2014. Of those who were initially non-obese who attended follow-up, 189/1270 (14.9%) [64% women] had developed GO (annual-incidence 2.13%) and 206/947 (21.9%) [56.3% women] had developed CO (annual incidence 3.12%) after 7 years. TBF and VFP significantly correlated with incident GO and CO (p<0.001). Female gender (OR-1.78, p<0.001; 2.81, p<0.001) and NAFLD (OR-2.93, p<0.001; OR-2.27, p<0.001) independently predicted incident GO and CO respectively. CONCLUSION: The prevalence and incidence of GO and CO were high in this cohort. Both incident GO and CO were strongly associated with female gender and NAFLD.Item Lean non-alcoholic fatty liver disease (Lean-NAFLD): characteristics and risk factors from a community cohort follow up study(Sri Lanka Medical Association, 2016) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyaratna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is usually associated with obesity. However, some NAFLD patients are lean. We assessed the characteristics and risk factors for lean-NAFLD. METHOD: In a community cohort follow up study (initial screening-2007, re-evaluation-2014), NAFLD was established on USS criteria and exclusion of alcohol overuse and secondary causes. Lean (BMI <23 kg/m2) and non-lean (BMI ≥23 kg/m2) NAFLD were compared. The two groups were compared for differences in gender, diabetes, hypertension, hypertriglyceridemia, low-HDL, weight and waist circumference (WC) at baseline. They were also compared for differences in development of incident diabetes, hypertension, hypertriglyceridemia, low-HDL, and change in weight and WC. RESULTS: 678 (69.6%) individuals with NAFLD detected in 2007 presented for follow up in 2014. 78(11.5%) [males-32(41%); mean-age 53.7(SD-7.1) years] were lean and 600(88.5%) [males-191(31.8%); mean-age 52.3(SD-7.5) years] were non-lean. Hypertension (p=0.007) and a smaller WC (<90cm for males, <80cm for females) (p<0.001) were associated with lean-NAFLD. After 7 years, change in BMI was less (p=0.022) among lean-NAFLD. There were no differences in change in WC or incident metabolic co-morbidities. Of those who did not have NAFLD in 2007, 746 developed incident NAFLD in 2014; lean-NAFLD 193/746 (25.9%) [males-100(51.8%); mean age 59.6(SD-7.5)], non-lean-NAFLD 553/746 (74.1%) [males-201(36.3%); mean age 58.2(SD-7.7)]. On logistic regression analysis, presence of diabetes (p=0.002, OR 2.1) and raised WC (p=0.003, OR 1.7) were associated with incident lean-NAFLD. CONCLUSIONS: Among individuals with NAFLD, lean-NAFLD is associated with hypertension and smaller WC. In the community, diabetes and bigger WC predict incident lean-NAFLD.Item Incidence and risk factors for non-alcoholic fatty liver disease in an urban, adult Sri Lankan population – a community cohort follow-up study(Sri Lanka Medical Association, 2016) Niriella, M.A.; Kasturiratne, A.; de Silva, S.T.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyarathna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.INTRODUCTION: In 2007, we reported a 33% prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with PNPLA3(rs738409) gene polymorphism in an urban, adult Sri Lankan population. OBJECTIVES: This study investigated incidence and risk factors for NAFLD after seven years follow-up. METHOD: The study population (42-71-year-olds, selected by age-stratified random sampling from the Ragama MOH area) was screened initially in 2007 and re-evaluated in 2014. On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on established ultrasound criteria, safe alcohol consumption and absence of hepatitis B/C markers. Non-NAFLD controls did not have any ultrasound criteria for NAFLD. An updated case-control genetic association study for 10 selected genetic variants and incident NAFLD was also performed. RESULTS: 2155/2985 (72.2%) of the original cohort attended follow-up [1244-women, 911-men; mean-age 59.2(SD, 7.7) years]. 1322 [839 women; mean-age 58.9 (SD, 7.6) years] had NAFLD. Out of 795 [466 women] who initially did not have NAFLD, 365 [226 women, mean-age 58.6(SD,7.9) years] had developed NAFLD after 7 years (annual incidence-6.6%). Increased waist circumference [p=0.001], BMI>23kg/m2 [p<0.001] and raised plasma triglycerides [p<0.05] independently predicted incident NAFLD. The updated genetic association study (1310 cases, 427 controls) showed borderline association with NAFLD at 2/10 candidate loci: PPP1R3B(rs4240624), PNPLA3(rs738409) (one-tailed p=0.044 and 0.033, respectively). CONCLUSIONS: In this community cohort follow-up study, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of metabolic syndrome, and showed tendency of association with PNPLA3 and PPP1R3B gene polymorphisms.Item Natural history of inflammatory bowel disease in Asia: A follow-up population-based cohort study(American Gastroenterological Association(AGA) Institute, Published by Elsevier Inc., 2014) Ng, S.C.; Tang, W.; de Silva, H.J.; Niriella, M.A.; Senanayake, Y.U.; Ooi, C.J.; Ling, K-L; Ong, D.E.; Goh, K.L.; Hilmi, I.; Ouyang, Q.; Wang, Y-F.; Hu, P.; Chen, M.; Zeng, Z.; Zhu, Z.; Wu, K.; Wang, X.; Pisespongsa, P.; Manatsathit, S.; Aniwan, S.; Simadibrata, M.; Abdullah, M.; Tsang, S.; Wong, T.; Leung, V.; Lo, F.H.; Hui, A.R.; Chow, C.M.; Yu, H.H.; Li, M.F.; Ng, K.K.; Ching, J.; Sung, J.J.Y.; Chan, F.K.L.BACKGROUND AND AIM: Data on the natural history of inflammatory bowel disease (IBD) in population-based setting in Asia are scarce. It is not clear if IBD disease course differs between Asian and Western cohorts. METHODS: In a population-based incident cohort from eight countries in Asia, we identified 259 IBD patients diagnosed between 2011 and 2013, including 158 ulcerative colitis (UC) and 101 Crohn's disease (CD) with a median follow up of 15 months (range, 12-31 months). The risk of disease extent and behaviour change according to the Montreal classification, and probability of medical or surgical therapy were prospectively assessed. RESULTS: Median age at diagnosis was 29 years (Interquartile range, IQR, 20-44) for CD, and 41 years (IQR, 30-54) for UC. At diagnosis, in CD, ileo-colonic disease (51%) and inflammatory behaviour (67%) were the most frequent phenotype. At one year, cumulative probability of behavior change from inflammatory to stricturing or penetrating disease was 18%, and cumulative rate of colectomy was 8%. In CD cumulative probabilities of receiving 5-aminosalicylic acid (5-ASA), corticosteroids, immune-suppressants and anti-tumor necrosis factor therapy were 61%, 43%, 66% and 10%, respectively, at one year. In UC, disease extent at diagnosis was evenly distributed including 31% with proctitis, 37% with left sided disease and 32% with extensive colitis. Disease extension occurred during follow-up in 19% of patients. Cumulative rate of colectomy at one year was 1%. In UC cumulative probabilities of receiving 5-ASA, corticosteroids and immunesuppressants were 91%, 28% and 13%, respectively at one year. There were two mortalities at maximal follow-up from lung carcinoma and severe sepsis. CONCLUSION: In this populationbased follow-up study, clinical presentation and early disease course in Asian IBD patients appear comparable to that of Western patients. Progression to complicated behavior and accelerated use of immunesuppressants is common in CD. Early surgical rate for UC in Asia remains low. Understanding the natural history of IBD in our population can help optimize therapeutic interventions. Reference: SC Ng, et al. Incidence and Phenotype of Inflammatory Bowel Disease, Based on Results from the Asia-Pacific Crohn's and Colitis Epidemiologic Study. Gastroenterology 2013; 145(1):158-165Item Profile of gastric varices among Sri Lankan cirrhotics(Wiley Blackwell Scientific Publications, 2012) Ranawaka, C.K.; Mettananda, K.C.D.; de Alwis, R.; Miththinda, J.K.N.D.; Wijewantha, H.S.; Niriella, M.A.; Dassanayake, A.S.; de Silva, A.P.; de Silva, H.J.BACKGROUND AND AIMS: Gastric varices (GV) can result in life threatening bleeding with a higher mortality than esophageal varices. There have been no studies on the characteristics of GV among Sri Lankan cirrhotics. Aim of this study was to perform a descriptive analysis of GV among a cohort of Sri Lankan cirrhotic population. METHODS: We analyzed medical records of all upper gastrointestinal endoscopies performed on cirrhotics, at the University Endoscopy Unit, Colombo North Teaching Hospital, Ragama, Sri Lanka from 2006 to 2011. Characteristics of GV, demographics, indications and fi ndings at endoscopy were analyzed and they were compared among patients with Oesophageal varices (EV). RESULTS: Out of 641 cirrhotics screened, 628 had a complete data set for analysis. GV was detected in 70 (11%) patients; male:female 8.7:1.3; mean age 55 (SD = ± 10.7) years. From these 48/70 had EV (Gastro Oesophageal Varices GOV1 – 18/48, GOV2 – 30/48) in addition to GV. Only 22/70 had Isolated GV (IGV1–10, IGV2–12). Among patients with GV 38 (54%) had portal hypertensive gastropathy and 3 (4%) had gastric antral vascular ectasia. Nineteen (27%) of GV were detected on presentations with UGIB (6 with IGV, 13 with GOV), whereas 51 (73%) were detected on routine screening. EV was detected in 288 (46%) of cirrhotics (Isolated EV 240, GOV 48). Seventy seven (32%) of EV were detected on presentations with UGIB, whereas 163 (68%) were detected on routine screening. There was no statistically significant difference on presentation with UGIB between isolated EV (77/240) vs. IGV (6/22) patients (p = 0.64; χ2 = 0.2). CONCLUSION: The profi le of GV among our cirrhotics is comparable to previous reports from other centres. Findings suggest that in cirrhotic patients presenting with UGIB, a careful search for the presence of GV is as important as identifying EV, even among patients who have EV.Item Association between road accidents and minimal hepatic encephalopathy in a cohort of Sri Lankan cirrhotic drivers(Wiley Blackwell Scientific Publications, 2014) Subasinghe, S.K.C.E.; Nandamuni, Y.; Ranasinghe, S.; Kodisinghe, K.; Niriella, M.A.; de Silva, A.P.; de Silva, H.J.OBJECTIVE: Minimal hepatic encephalopathy (MHE) has no recognizable clinical symptoms of hepatic encephalopathy (HE) but has mild cognitive and psychomotor deficits which can interfere with executive decision making and psychomotor speed. It affects driving ability and previous studies in Western countries have demonstrated an association between MHE and increased road accidents. Our objective was to investigate this association in a cohort of Sri Lankan cirrhotic drivers. METHODS: A prospective, case controlled study ongoing study has been conducted in the Gastroenterology Clinic, University Medical Unit, North Colombo Teaching Hospital, Ragama, from August 2013. Patients with cirrhosis of any aetiology, without overt HE, who had been driving any vehicle during the past one month were subjected to 5 standard pencil-paper based psychometric tests used to detect MHE. Road accidents were recorded for both cirrhotic drivers with MHE and controls. Accidents were categorized as major when they resulted in hospitalization of the involved person/s, and minor when there were no serious injuries. RESULTS: Among 55 cirrhotic drivers with MHE [males, median age 53 years (range 30-60)], 7 (12.7%) reported any type of accident compared to 6 (10.9%) among 55 controls [males; median age 51 years (range 30-60)]. 2/55 (3.6%) cases and 2/55 (3.6%) controls reported minor accidents. There were no major accidents in either group. CONCLUSION: Preliminary results of this ongoing study do not indicate an increased frequency of road accidents in a cohort of Sri Lankan cirrhotic drivers with MHEItem 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 hepatitis B and hepatitis C infections and their relationship to injectable drug use in a cohort of Sri Lankan prison inmates(Sri Lanka Medical Association, 2015) Niriella, M.A.; Hapangama, A.; Luke, H.P.D.P.; Pathmeswaran, A.; Kuruppuarachchi, K.A.L.A.; de Silva, H.J.INTRODUCTION: Prisoners are considered to be at high risk for Hepatitis B (HBV) and Hepatitis C (HCV) virus infections. This is attributed to intravenous drug use and high-risk sexual behaviour. There are no published studies on HBV and HCV among prison inmates or injecting drug users in Sri Lanka. OBJECTIVES: To determine prevalence of HBV and HCV infections, and their relationship to injectable drug use among Sri Lankan prisoners. METHODS: We investigated 393 (median age 42 years (range 16 to 93); 82% males) randomly selected inmates of Mahara and Welikada prisons. RESULTS: Though 167 (42.5%) admitted drug abuse, only 17 (4.3%) had ever used intravenous drugs. Twelve (70.6%) of them reported sharing needles. One inmate was positive for HBsAg but was negative for HBV-DNA. Twenty seven (6.9%) were positive for anti-HCV antibodies, of whom only 2 (0.5%) were positive for HCV-RNA. None of the injecting drug users were positive for HBV-DNA or HCV-RNA. CONCLUSIONS: The prevalence of HBV and HCV infections as well as injecting drug use was very low among this cohort of Sri Lankan prisoninmates