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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Is being barefoot, wearing shoes and physical activity associated with knee osteoarthritis pain flares? Data from a usually barefoot Sri Lankan cohort(Oxford, 2021) Atukorala, I.; Pathmeswaran, A.; Batuwita, N.; Rajapaksha, N.; Ratnasiri, V.; Wijayaratne, L.; de Silva, M.; Chang, T.; Zhang, Y.; Hunter, D.J.AIM: To identify the association between hours of being barefoot/wearing footwear, physical activity (PA) and knee osteoarthritis pain flares (KOAF). METHODS: Persons with a diagnosis of knee osteoarthritis, who reported previous KOAF, were followed up in a 3 months long telephone-based case-crossover study. Exposures to risk factors were assessed every 10 days and whenever the participants experienced a KOAF. Conditional logistic regression examined associations of KOAF with following: hours of being barefoot/using footwear and PA performed (P < .05). RESULTS: There were 260 persons recruited, of whom 183 continued longitudinal follow up. Of them, 120 persons had at least one valid KOAF and control period. Participants were female (90%) with mean (SD) age and body mass index of 59.9 (7.0) years, 28.0 (5.0) kg/m2 respectively. Participants were barefoot for a mean duration of 12.7 hours (SD 4.6) and used footwear for 5.1 (SD 4.7) hours daily; 99% wore heel heights <2.5 cm. Duration of being barefoot, 1 and 2 days before, demonstrated reduced multivariate odds of KOAF (odds ratio [OR] = 0.85; 95% CI 0.80-0.90). Moderate PA performed 1, 2 days prior was associated with a significantly increased risk of KOAF (multivariate OR 4.29; 2.52-7.30 and OR 3.36; 2.01-5.61). Similarly, hours of using footwear 1 and 2 days before flare demonstrated increased odds of KOAF (OR 1.15; 1.07-1.23 and 1.10; 1.03-1.18). CONCLUSIONS: Increased duration of being barefoot 1 to 2 days before is associated with reduced risk of KOAF. Performing moderate PA 1 to 2 days before was associated with an increased risk of KOAF. KEYWORDS: knee osteoarthritis pain.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 The role of reflux in the genesis of respiratory symptoms in a cohort of adult asthmatics in Sri Lanka(Wiley-Blackwell, 2010) Amarasiri, L.; Ranasinha, C.D.; Pathmeswaran, A.; de Silva, H.J.INTRODUCTION: The oesophagus and airways have a common origin. Reflux related respiratory symptoms may be triggered by aspiration of gastric refluxate into airways or a vagally mediated oesophago-tracheo-bronchial. This association has not been reported previously in Sri Lanka. The aim of this study was to describe the association between gastro-oesophageal reflux (GOR) events and respiratory symptoms in a cohort of adult asthmatics in Sri Lanka. METHODS: Thirty stable, mild asthmatics (American Thoracic Society criteria) underwent dual-sensor ambulatory oesophageal pH monitoring. Respiratory symptoms (cough, wheeze, difficult breathing, chest tightness) during monitoring were recorded and correlated with reflux events. RESULTS: Both proximal and distal GOR parameters were significantly higher in asthmatics than controls (P < 0.050; Mann–Whitney U-test). However, there was no difference in any parameter between asthmatics with and without respiratory symptoms. Abnormal proximal acid reflux was documented in 66.7% and distal reflux in 73.3% of 30 asthmatics. Of 102 respiratory symptoms in all asthmatics, majority (72%) were cough episodes. In total, 93% of coughs, 81% of wheeze and all of chest tightness was reflux-associated, where in most, reflux events preceded respiratory symptoms. Of 15 asthmatics with respiratory symptoms, acid exposure was normal in 4 (26%), abnormally high in proximal oesophagus in 9 (60%) and abnormally high in the distal oesophagus in 11 (73%) and abnormal at both levels in 8 (53%). Most reflux events in asthmatics occurred in the upright position. CONCLUSION: Asthmatics have more GOR and associated respiratory symptoms than non-asthmatic volunteers, with reflux episodes preceding respiratory symptoms in most cases. Distal GOR and upright acid exposure was more prominent than proximal GOR.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 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