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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Changing phenotype, early clinical course and clinical predictors of inflammatory bowel disease in Sri Lanka: a retrospective, tertiary care-based, multi-centre study(BioMed Central, 2021) Niriella, M.A.; Liyanage, I.K.; Kodisinghe, S.K.; de Silva, A.P.; Jayatissa, A.V.G.A.M.; Navarathne, N.M.M.; Peiris, R.K.; Kalubovila, U.P.; Kumarasena, S.R.; Jayasekara, R.W.; de Silva, H.J.BACKGROUND: Inflammatory bowel disease (IBD) is increasing in the Asia-Pacific region, with changes in disease phenotype and course. We aimed to assess the changing phenotypes of IBD over ten years, describe the early clinical course (ECC) and identify the clinical predictors (CP) of poor outcomes among a large, multi-centre, cohort of Sri Lankan IBD patients. METHODS: We included patients [diagnosed between June/2003-December/2009-Group-1(G1), January/2010-June/2016-Group-2(G2)] with ulcerative colitis (UC) and Crohn disease (CD) from five national-referral centres. Changing phenotype from G1 to G2, ECC (disease duration < 3-years) and CP of poor outcomes (disease duration ≥ 1-year) was assessed. Poor outcomes were complicated-disease (CompD-stricturing/penetrating-CD, extensive-UC/pancolitis, perforation/bleeding/colectomy/malignancy) and treatment-refractory disease (TRD-frequently-relapsing, steroid-dependent/refractory and biologic use). RESULTS: 375 (UC-227, CD-148) patients were recruited. Both G1/G2 had more UC than CD (77% vs 23%, 54.5 vs 45.5 respectively, p < 0.01). Increase of CD from G1-to-G2 was significant (23-45.4%, p < 0.001). In both groups, left-sided colitis (E2) and ileo-colonic (L3)/non-stricturing, non-penetrating disease behaviour (B1) CD predominated. Extensive-colitis (E3) (36.4% vs 22.7, p < 0.05) and stricturing-CD (B2) (26.1% vs 4.0%, p < 0.01) was commoner in G1. ECC was assessed in 173-patients (UC-94, CD-79). Aggressive disease behaviour and TRD were low among both UC and CD. Immunomodulator use was significantly higher among CD than UC (61.5% vs 29.0% respectively, p < 0.01). Anti-TNF use was low among both groups (UC-3.2%, CD-7.7%). Disease complications among UC [bleeding (2.1%), malignancy-(1.1%), surgery-(2.1%)] and CD [stricture-(3.9%), perforation-(1.3%), malignancy-(1.3%), surgery-(8.9%)] were generally low. CPs were assessed in 271-patients (UC-163, CD-108). Having a family history of IBD (for UC), extraintestinal manifestation (EIM), severe disease at presentation, being in younger age categories and severe disease at presentation, (for both UC and CD) predicted poor outcomes. CONCLUSION: There was an increase in CD over time without change in disease phenotype for both UC and CD. A relatively benign ECC was observed. Family history (UC), EIMs (UC/CD), severe disease at presentation (UC/CD), younger age (CD/UC) CPs of poor outcomes. KEYWORDS: Clinical course; Clinical predictors; Crohn disease; Inflammatory bowel disease; Phenotype; Sri Lanka; Ulcerative colitis.Item Non-resolution of non-alcoholic fatty liver disease (NAFLD) among urban, adult Sri Lankans in the general population: A prospective, cohort follow-up study.(Public Library of Science, 2019) Niriella, M.A.; Kasturiratne, A.; Beddage, T.; Ediriweera, D.S.; de Silva, S.T.; Perera, K.R.; Subasinghe, C.E.; Kodisinghe, S.K.; Piyaratna, T.C.; Rishikesawan, V.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.BACKGROUND: There are few studies investigating the natural course of non-alcoholic fatty liver disease (NAFLD) in the community. We assessed resolution of NAFLD in a general population cohort of urban Sri Lankans adults. METHODS: Participants were selected by age-stratified random sampling from electoral lists. They were initially screened in 2007 and re-evaluated in 2014. On both occasions structured interview, anthropometric-measurements, liver ultrasonography, and biochemical/serological tests were performed. NAFLD was diagnosed on ultrasound criteria for fatty liver, safe-alcohol consumption (<14-units/week for men, <7-units/week for women) and absence of hepatitis B/C markers. Non-NAFLD was diagnosed on absence of any ultrasound criteria for fatty liver and safe-alcohol consumption. Resolution of NAFLD was defined as absence of ultrasound criteria for fatty liver. Changes in anthropometric indices [Weight, Body-Mass-Index (BMI), waist-circumference (WC), waist-hip ratio (WHR)], clinical [systolic blood pressure (SBP), diastolic blood pressure (DBP)] and biochemical measurements [Triglycerides (TG), High Density Lipoprotein (HDL), Total Cholesterol (TC), HbA1c%] at baseline and follow-up were compared. RESULTS: Of the 2985 original study participants, 2148 (71.9%) attended follow-up after 7 years. This included 705 who had NAFLD in 2007 and 834 who did not have NAFLD in 2007. Out of 705 who had NAFLD in 2007, 11(1.6%) changed their NAFLD status due to excess alcohol consumption. After controlling for baseline values, NAFLD patients showed significant reduction in BMI, weight, WHR, HDL and TC levels and increase in HbA1c levels compared to non-NAFLD people. Despite this, none of them had complete resolution of NAFLD. CONCLUSION: We did not find resolution of NAFLD in this general population cohort. The observed improvements in anthropometric, clinical and biochemical measurements were inadequate for resolution of NAFLD.nal Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo, Japan.Item Percentage of small platelets on peripheral blood smear and Child-Turcott-Pugh class can predict the presence of oesophageal varices in newly diagnosed patients with cirrhosis: development of a prediction model for resource limited settings(BioMed Central, 2019) Perera, K.; Kodisinghe, S.K.; Ediriweera, D.S.; Moratuwagama, D.; Williams, S.; Pathmeswaran, A.; Niriella, M.A.; de Silva, H.J.BACKGROUND:In cirrhosis upper-gastrointestinal-endoscopy (UGIE) identifies oesophageal varices (OV). UGIE is unavailable in most resource-limited settings. Therefore, we assessed prediction of presence of OV using hematological parameters (HP) and Child-Turcott-Pugh (CTP) class.METHODS:A prospective study was carried out on consecutive, consenting, newly-diagnosed patients with cirrhosis, in the University Medical Unit, Colombo North Teaching Hospital, Ragama, Sri Lanka from April 2014-April 2016. All patients had UGIE to evaluate presence and degree of OV, prior to appropriate therapy. HP (full blood count with indices using automated analyzer and peripheral blood smear using Leishmann stain) and CTP class were assessed on admission. Linear logistic regression model was developed to predict OV using HP and CTP class.RESULTS:54-patients with cirrhosis were included [14(26%), 24(44%) and 16(30%) belonged to CTP class A, B and C respectively]. 37 had varices [CTP-A 4/14(26.6%), CTP-B 19/24(79.2%), CTP-C 14/16(87.5%)] on UGIE. Generalized linear model fitting showed decreasing percentage of small platelets (%SP) (P = 0.002), CTP-B (P = 0.003) and CTP-C (P = 0.003) compared to CTP-A had higher probability of having OV. The model predicts the log odds for having OV = - 0.189 - (0.046*%SP) + 2.9 [if CTP-B] + 3.7 [if CTP-C]. Based on receiver operating characteristic (ROC) analysis, a model value > - 0.19 was selected as the cutoff point to predict OV with 89%-sensitivity, 76%-specificity, 89%-positive predictive value and 76%-negative predictive value.CONCLUSIONS:We constructed a model using %SP on peripheral blood smear and CTP class. This model may be used to predict the presence of OV, in newly diagnosed patients with cirrhosis, with acceptable sensitivity and specificity, to prioritize the patients who deserve early UGIE in limited resource settingsItem Genetic associations of inflammatory bowel disease in a South Asian population(Baishideng Publishing Group, 2018) Niriella, M.A.; Liyanage, I.K.; Kodisinghe, S.K.; Silva, A.P.; Rajapakshe, N.; Nanayakkara, S.D.; Luke, D.; Silva, T.; Nawarathne, M.; Peiris, R.K.; Kalubovila, U.P.; Kumarasena, S.R.; Dissanayake, V.H.W.; Jayasekara, R.W.; de Silva, H.J.AIM: To estimate prevalence and phenotypic associations of selected inflammatory bowel disease (IBD)-associated genetic variants among Sri Lankan patients. METHODS: A case study of histologically confirmed ulcerative colitis (UC) or Crohn's disease (CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12B:rs1045431, IL23R:rs11805303, ARPC2:rs12612347, IRGM:rs13361189, IL26/IL22:rs1558744, CDH1:rs1728785, IL10:rs3024505, FCGR2A:rs3737240, PTGER4:rs4613763, IL17REL/PIM3:rs5771069, HNF4a:rs6017342, STAT3:rs744166, SMURF1:rs7809799, LAMB1:rs886774, HLA-DRB5, DQA1, DRB1, DRA:rs9268853, MST1, UBA7, and APEH:rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium (P > 10-3). To account for multiple hypothesis testing, P-values < 0.003 were considered significant. RESULTS: A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms (SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774 (LAMB1-gene) and UC (odds ratio (OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease (OR = 1.66, P < 0.001) and remained in remission (OR = 1.48, P < 0.001). A positive association was noted between rs10045431 (IL 12B gene) and upper gastrointestinal involvement in CD (OR = 4.76, P = 0.002). CONCLUSION: This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.Item Ideal amount of exercise for a healthy life: have we solved the goldilocks problem? – review of the literature(Endocrine Society of Sri Lanka, 2016) Muthukuda, D.T.; Kodisinghe, S.K.; Niriella, M.A.There is an increasing interest in the place of physical activity to counter the increasing risk of non-communicable diseases and its complications in the community. Debate remains just how much exercise is too little, too much or just right to improve health and longevity. This article reviews the present evidence of physical activity on mortality and the possible ideal recommendations on physical activity.Item Effect of audio and visual distraction on patients undergoing colonoscopy: a randomized controlled study(Stuttgart : Georg Thieme Verlag KG, 2016) de Silva, A.P.; Niriella, M.A.; Nandamuni, Y.; Nanayakkara, S.D.; Perera, K.R.P.; Kodisinghe, S.K.; Subasinghe, K.C.E.; Pathmeswaran, A.; de Silva, H.J.BACKGROUND AND STUDY AIMS : Colonoscopy can cause anxiety and discomfort in patients. Sedation and analgesia as premedication can lead to complications in the elderly and those with comorbidities. This has led to an interest in the use of audio-visual distraction during the colonoscopy. We compared the effects of audio (AD) versus visual distraction (VD) in reducing discomfort and the need for sedation during colonoscopy. PATIENTS AND METHODS: Consecutive patients undergoing colonoscopy were randomized into three groups: one group was allowed to listen to the music of their choice (AD), the second group was allowed to watch a movie of their choice (VD), and the third group was not allowed either distraction during colonoscopy and acted as a control (C). Patient controlled analgesia and sedation were administered to all three groups. We used 25 mg of pethidine in 5-mg aliquots and 2.5 mg of midazolam in 0.5-mg aliquots. All patients were assessed for perceived pain and willingness to repeat the procedure. Number of "top-ups" of sedation and total dose of pethidine and midazolam were noted. Patient cooperation and ease of procedure were assessed by the colonoscopist. RESULTS: In total, 200 patients were recruited [AD, n = 66 (32 males, median age 57 years); VD, n = 67 (43 males, median age 58 years); C, n = 67 (35 males, median age 59 years)]. The AD group had significantly less pain (P = 0.001), better patient cooperation (P = 0.001) and willingness to undergo a repeat procedure (P = 0.024) compared with VD and C groups. CONCLUSIONS: AD reduces pain and discomfort, improves patient cooperation and willingness to undergo a repeat procedure, and seems a useful, simple adjunct to low dose sedation during colonoscopy.Item Intestinal tuberculosis masquerading as difficult to treat Crohn disease: a case report(Biomed Central, 2016) Niriella, M.A.; Kodisinghe, S.K.; de Silva, A.P.; Hewavisenthi, J.; de Silva, H.J.BACKGROUND: Crohn disease has low prevalence in Sri Lanka while compared to the West, while intestinal tuberculosis is common in the region. Since clinical, endoscopic and investigation features of Crohn disease overlap with intestinal tuberculosis, differentiating these two conditions becomes a dilemma for the clinician in the intestinal tuberculosis endemic setting. An 18-year old Sri Lankan Muslim female presented with chronic abdominal pain and weight loss. Colonoscopy revealed an ulcerated ileocaecal valve and a terminal ileal stricture. Biopsy confirmed Crohn disease with no supportive features to suggest intestinal tuberculosis. Despite treatment with adequate immunosuppression she failed to improve and underwent a limited right hemicolectomy and terminal ileal resection. Histology confirmed intestinal tuberculosis and she made full recover with 6 months of anti-tuberculosis treatment. CONCLUSION: This case illustrates the importance of reviewing the diagnosis to include intestinal tuberculosis in an endemic setting, when already diagnosed Crohn disease is treatment refractory.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.