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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 The treatment of ulcerative colitis: from cure to a new disease(Ceylon Medical Association, 1994) de Silva, H.J.No abstract availableItem Mistakes in managing hepatocellular carcinoma and how to avoid them: a narrative review(Taylor and Francis Group, 2023) Niriella, M.A.; Dassanayake, U.; de Silva, H.J.INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common liver-related cancer and the third leading cause of worldwide cancer-related mortality. AREAS COVERED: There have been many updated guidelines on the management of HCC in the past few years. Given the increasing burden of HCC in clinical practice, knowledge of evidence-based standards of care for these patients is essential for any practitioner managing patients with HCC. Early detection and judicious treatment based on the stage of the HCC can improve patient outcomes. We performed a PubMed (MEDLINE database) search for the latest guidelines related to the screening, detection, diagnosis, staging, and management of HCC. We aim to highlight some major considerations and common mistakes in managing HCC and attempt to provide evidence-based recommendations. EXPERT OPINION: The field of HCC management is expected to evolve in the coming years. Increased emphasis on personalized treatment and precision medicine with earlier detection methods, the development of noninvasive diagnostic tools, increased focus on combination therapies and a shift toward more targeted treatments will become more critical.Item Hepatocellular carcinoma in Sri Lanka: Where do we stand?(Sri Lanka Medical Association, 2013) Siriwardana, R.C.; Liyanage, C.A.H.L.; Jayatunge, D.S.P.; Dassanayaka, A.; Gunetileke, M.G.; Niriella, M.A.; Sirigampola, C.; Upasena, A.; de Silva, H.J.INTRODUCTION AND OBJECTIVES:Hepato-cellular carcinoma (HCC) is the sixth commonest cancer worldwide. We studied 105 consecutive patients with HCC in a single tertiary care centre. METHODS: North Colombo Liver Unit maintains a prospective database of HCC since September 2011. There were 105 entries by February 2013. Decision on the best form of treatment was taken at a multidisciplinary meeting. RESULTS: The median age at presentation was 63 years (range 12-79). Patients were predominantly male 93 (87%). Alcohol consumption above the safe limit was reported in 47 (45%). Hepatitis B surface antigen or C antibody was not detected in any of the patients. Background liver cirrhosis was evident in 59 (79%). Forty two (46%) patients had single nodular tumours while in 20 (21%) it was diffusely infiltrating. Portal vein invasion was seen in 22 (20 %). Median alpha-feto protein (AFP) level was 57.25 mg/ml (1.16- 94120 ng/ml; n=72). Twenty four (33%) patients had AFP level > 400u/l. Surgery was performed in 20 (19%), liver transplant in 2 (1.9%), radio frequency ablation or alcohol ablation in 8 (7.6%), trans arterial chemo embolization (TACE) in 44 (41.9%) and sorafmib was prescribed in four patients. Overall mean survival was 15 months. In the ‘no treatment’ group, mean survival was 4 months. Surgery group had a mean survival of 20 months. CONCLUSION: Hepatitis B is not a risk factor for HCC in Sri Lankans. Median survival without treatment is 4 months.Item 'Mistakes in managing non-alcoholic fatty liver disease and how to avoid them'(Informa Health Care, 2023) Niriella, M.A.; Dassanayake, U.; de Silva, H.J.Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease. NAFLD is estimated to affect 25% of the global population. Therefore, it is widely encountered in primary care. A proportion of patients with NAFLD need a specialist referral, evaluation and follow-up.There have been many updated guidelines on the management of NAFLD in the past few years. Given the burden of NAFLD in the community and its cardiovascular and liver-related adverse outcomes, knowledge of evidence-based standards of care for these patients is essential for any practitioner managing patients with NAFLD. As an asymptomatic disease in the early stages, NAFLD can lead to many mistakes in its management.We aim to highlight some common mistakes in managing NAFLD and attempt to provide evidence-based recommendations.Item A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids(American Society of Human Genetics., 2022) Ramdas, S.; Judd, J.; Graham, S.E.; Kanoni, S.; Wang, Y.; Surakka, I.; Wenz, B.; Clarke, S.L.; Chesi, A.; Wells, A.; Bhatti, K.F.; Vedantam, S.; Winkler, T.W.; Locke, A.E.; Marouli, E.; Zajac, G.J.M.; Wu, K.H.; Ntalla, I.; Hui, Q.; Klarin, D.; Hilliard, A.T.; Wang, Z.; Xue, C.; Thorleifsson, G.; Helgadottir, A.; Gudbjartsson, D.F.; Holm, H.; Olafsson, I.; Hwang, M.Y.; Han, S.; Akiyama, M.; Sakaue, S.; Terao, C.; Kanai, M.; Zhou, W.; Brumpton, B.M.; Rasheed, H.; Havulinna, A.S.; Veturi, Y.; Pacheco, J.A.; Rosenthal, E.A.; Lingren, T.; Feng, Q.; Kullo, I.J.; Narita, A.; Takayama, J.; Martin, H.C.; Hunt, K.A.; Trivedi, B.; Haessler, J.; Giulianini, F.; Bradford, Y.; Miller, J.E.; Campbell, A.; Lin, K.; Millwood, I.Y.; Rasheed, A.; Hindy, G.; Faul, J.D.; Zhao, W.; Weir, D.R.; Turman, C.; Huang, H.; Graff, M.; Choudhury, A.; Sengupta, D.; Mahajan, A.; Brown, M.R.; Zhang, W.; Yu, K.; Schmidt, E.M.; Pandit, A.; Gustafsson, S.; Yin, X.; Luan, J.; Zhao, J.H.; Matsuda, F.; Jang, H.M.; Yoon, K.; Gomez, C.M.; Pitsillides, A.; Hottenga, J.J.; Wood, A.R.; Ji, Y.; Gao, Z.; Haworth, S.; Mitchell, R.E.; Chai, J.F.; Aadahl, M.; Bjerregaard, A.A.; Yao, J.; Manichaikul, A.; JaneLee, W.; Hsiung, C.A.; Warren, H.R.; Ramirez, J.; Jensen, J.B.; Kårhus, L.; Goel, A.; Lleal, M.S.; Noordam, R.; Mauro, P.; Matteo, F.; McDaid, A.F.; Marques-Vidal, P.; Wielscher, M.; Trompet, S.; Sattar, N.; Møllehave, L.T.; Munz, M.; Zeng, L.; Huang, J.; Yang, B.; Poveda, A.; Kurbasic, A.; Schönherr, S.; Forer, L.; Scholz, M.; Galesloot, T.E.; Bradfield, J.P.; Ruotsalainen, S.E.; Daw, E.W.; Zmuda, J.M; Mitchell, J.S.; Fuchsberger, C.; Christensen, H.; Brody, J.A.; Le, P.; Feitosa, M.F.; Wojczynski, M.K.; Hemerich, D.; Preuss, M.; Mangino, M.; Christofidou, P.; Verweij, N.; Benjamins, J.W.; Engmann, J.; Noah, T.L.; Verma, A.; Slieker, R.C.; Lo, K.S.; Zilhao, N.R.; Kleber, M.E.; Delgado, G.E.; Huo, S.; Ikeda, D.D.; Iha, H.; Yang, J.; Liu, J.; Demirkan, A.; Leonard, H.L.; Marten,J.; Emmel, C.; Schmidt, B.; Smyth, L.J.; Cañadas-Garre, M.; Wang, C.; Nakatochi, M.; Wong, A.; Hutri-Kähönen , N.; Sim, X.; Xia, R.; Huerta-Chagoya, A.; Fernandez-Lopez, J.C.; Lyssenko, V; Nongmaithem, S.S.; Sankareswaran, A.; Irvin, M.R.; Oldmeadow, C.; Kim, H.N.; Ryu, S.; Timmers, P.R.H.J; Arbeeva, L.; Dorajoo, R.; Lange, L.A.; Prasad, G.; Lorés-Motta, L.; Pauper, M.; Long, J.; Li, X.; Theusch, E.; Takeuchi, F.; Spracklen, C.N.; Loukola, A.; Bollepalli, S.; Warner, S.C.; Wang, Y.X.; Wei, W.B.; Nutile, T.; Ruggiero, D.; Sung,Y.J.; Chen, S.; Liu, F.; Yang, J.; Kentistou, K.A.; Banas, B.; Morgan, A.; Meidtner, K.; Bielak, L.F.; Smith, J.A.; Hebbar, P.; Farmaki, A.E.; Hofer, E.; Lin, M.; Concas, M.P.; Vaccargiu, S.; Most, P.J.; Pitkänen, N.; Cade, B.E.; Laan, S.W.; Chitrala, K.N.; Weiss, S.; Bentley, A.R.; Doumatey, A.P.; Adeyemo, A.A.; Lee, J.Y.; Petersen, E.R.B.; Nielsen, A.A.; Choi, H.S.; Nethander, M.; Nethander, M.; Freitag-Wolf, S.; Southam, L.; Rayner, N.W.; Wang, C.A.; Lin, S.; Wang, J.S.; Couture, C.; Lyytikäinen, L.P.; Nikus, K.; Partida, G.C.; Vestergaard, H.; Hidalgo, B.; Giannakopoulou, O.; Cai, Q.; Obura, M.O.; Setten, J.; He, K.Y.; Tang, H.; Terzikhan, N.; Shin, J.H.; Jackson, R.D.; Reiner, A.P.; Martin, L.W.; Chen, Z.; Li, L.; Kawaguchi, T.; Thiery, J.; Bis, J.C.; Launer, L.J.; Li, H.; Nalls, M.A.; Raitakari, O.T.; Ichihara, S.; Wild, S.H.; Nelson, C.P.; Campbell, H.; Jäger, S.; Nabika, T.; Al-Mulla, F.; Niinikoski, H.; Braund, P.S.; Kolcic, I.; Kovacs, P.; Giardoglou, T.; Katsuya, T.; Kleijn, D.; Borst, G.J.; Kim, E.K.; Adams, H.H.H.; Ikram, M.A.; Zhu, X.; Asselbergs, F.W.; Kraaijeveld, A.O.; Beulens, J.W.J.; Shu, X.O.; Rallidis, L.S.; Pedersen, O.; Hansen, T.; Mitchell, P.; Hewitt, A.W.; Kähönen, M.; Pérusse, L.; Bouchard, C.; Tönjes, A.; Chen, Y.D.I; Pennell, C.E.; Mori, T.A.; Lieb, W.; Franke, A.; Ohlsson, C.; Mellström, D.; Cho, Y.S.; Lee, H.; Yuan, J.M.; Koh, W.P.; Rhee, S.Y.; Woo, J.T.; Heid, I.M.; Stark, K.J.; Zimmermann, M.E.; Völzke, H.; Homuth, G.; Homuth, G.; Evans, M.K.; Zonderman, A.B.; Polasek, O.; Pasterkamp, G.; Hoefer, I.E.; Redline, S.; Pahkala, K.; Oldehinkel, A.J.; Snieder, H.; Biino, G.; Schmidt, R.; Schmidt, H.; Bandinelli , S; Dedoussis, G.; Thanaraj, T.A.; Peyser, P.A.; Kato, N.; Schulze, M.B.; Girotto, G.; Böger, C.A.; Jung, B.; Joshi, P.K.; Bennett, D.A.; Jager, P.L.D.; Lu, X.; Mamakou, V.; Brown, M.; Caulfield, M.J.; Munroe, P.B.; Guo, X.; Ciullo, M.; Jonas, J.B.; Samani, N.J.; Kaprio, J.; Pajukanta, P.; Luna, T.T.; Salinas, C.A.A.; Adair, L.S.; Bechayda, S.A.; de Silva, H.J.; Wickremasinghe, A.R.; Krauss, R.M.; Wu, J.Y.; Zheng,W.; Hollander, A.I.; Bharadwaj, D.; Correa, A,; Wilson, J.G.; Lind, L.; Heng, C.K.; Nelson, A.E.; Golightly, Y.M.; Wilson, J.F.; Penninx, B.; Kim, H.L.; Attia, J.; Scott, R.J.; Rao, D.C.; Arnett, D.K.; Walker, M.; Scott, L.J.; Koistinen, H.A.; Chandak, G.R.; Mercader, J.M.; Villalpando, C.G.; Orozco, L.; Fornage, M.; Tai, E.S.; Dam, R.M.; Lehtimäki, T.; Chaturvedi, N.; Yokota, M.; Liu, J.; Reilly, D.F.; McKnight, A.J.; Kee, F.; Jöckel, K.H.; McCarthy, M.I.; Palmer, C.N.A.; Vitart, V.; Hayward, C.; Simonsick, E.; Duijn, C.M; Jin, Z.B.; Jin, Z.B.; Lu, F.; Hishigaki, H.; Lin, X.; März, W.; Gudnason, V.; Tardif, J.C.; Lettre, G.; Hart, L.M.T.; Elders, P.J.M.; Rader, D.J.; Loos, S.M.; Province, M.A.; Parra, E.J.; Cruz, M.; Psaty, B.M.; Brandslund, I.; Pramstaller, P.P.; Rotimi, C.N.; Christensen, K.; Ripatti, S.; Widén, E.; Hakonarson, H.; Grant, S.F.A.; Kiemeney, L.; de Graaf, J.; Loeffler, M.; Kronenberg, F.; Gu, D.; Erdmann, J.; Schunkert, H.; Franks,P.W.; Linneberg, A.; Jukema, J.W.; Khera, A.V.; Männikkö, M.; Jarvelin, M.R.; Kutalik, Z.; Francesco, C.; Kanamori, D.O.M.; Dijk, K.W.; Watkins, H.; Strachan, D.P.; Grarup, N.; Sever, P.; Poulter, N.; Sheu, W.H.H.; Rotter, J.I.; Dantoft, T.M.; Karpe, F.; Neville, M.J.; Timpson, N.J.; Cheng, C.Y.; Wong, T.Y.; Khor, C.C.; Li, H.; Sabanayagam, C.; Peters, A.; Gieger, C.; Hattersley, A.T.; Pedersen, N.L.; Magnusson, P.K.E.; Boomsma, D.I.; de Geus, E.J.C.; Cupples, L.A.; Meurs, J.B.J.; Ikram, A.; Ghanbari, M.; Larsen, P.G.; Huang, W.; Kim, Y.J.; Tabara, Y.; Wareham, N.J.; Langenberg, C.; Zeggini, E.; Tuomilehto, J.; Kuusisto, J.; Laakso, M.; Ingelsson, E.; Abecasis, G.; Chambers, J.C.; Kooner, J.S.; de Vries, P.S.; Morrison, A.C.; Hazelhurst, S.; Ramsay, M.; North, K.E.; Daviglus, M.; Kraft, P.; Martin, N.G.; Whitfield, J.B.; Abbas, S.; Saleheen, D.; Walters, R.G.; Holmes, M.V.; Black, C.; Smith, B.H.; Baras, A.; Justice, A.E.; Buring, J.E.; Ridker, P.M.; Chasman, D.I.; Kooperberg, C.; Tamiya, G.; Yamamoto, M.; Heel, D.A.; Trembath, R.C.; Wei, W.Q.; Jarvik, G.P.; Namjou, B.; Hayes, M.G.; Ritchie, M.D.; Jousilahti, P.; Salomaa, V.; Hveem, K.; Åsvold, B.O.; Kubo, M.; Kamatani, Y.; Okada, Y.; Murakami, Y.; Kim, B.J.; Thorsteinsdottir, U.; Stefansson, K.; Zhang, J.; Chen, Y.E.; Ho, Y.L.; Lynch, J.A.; Tsao, P.S.; Chang, K.M.; Cho, K.; O'Donnell, C.J.; Gaziano, J.M.; Wilson, P.; Mohlke, K.L.; Frayling, T.M.; Hirschhorn, J.N.; Kathiresan, S.; Boehnke, M.; Million Veterans Program; Global Lipids Genetics Consortium; Grant, S.; Natarajan, P.; Sun, Y.V.; Morris, A.P.; Deloukas, P.; Peloso, G.; Assimes, T.L.; Willer, C.J.; Zhu, X.; Brown, C.D.A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.Item Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation(Nature Publishing Company, New York, 2022) Mahajan, A.; Spracklen, C.N.; Zhang, W.; Ng, M.C.Y.; Petty, L.E.; Kitajima, H.; Yu, G.Z.; Rüeger, S.; Speidel, L.; Kim, Y.J.; Horikoshi, M.; Mercader, J.M .; Taliun, D.; Moon, S.; Kwak, S.H.; Robertson, N.R.; Rayner, N.W.; Loh, M.; Kim, B.; Chiou, J.; Miguel-Escalada, I.; Parolo, P.D.B.; Lin, K.; Bragg, F.; Preuss, M.H.; Takeuchi, F.; Nano, J.; Guo, X.; Lamri, A.; Nakatoch, M.; Scott, R.A.; Lee, J.J.; Huerta-Chagoya, A.; Graff, M.; Chai, J.F.; Parra, E. J.; Yao, J.; Bielak, L.F.; Tabara, Y.; Hai, Y.; Steinthorsdottir, V.; Cook, J.P.; Kals, M.; Grarup, N.; Schmidt, E.M.; Pan, I.; Sofer, T.; Wuttke, M.; Sarnowski, C.; Gieger, C.; Nousome, D.; Trompet, S.; Long, J.; Sun, M.; Tong, L.; Chen, W.M.; Ahmad, M.; Noordam, R.; Lim, V.J.Y.; Tam, C.H.T.; Joo, Y.Y.; Chen, C.H.; Raffield, L.M.; Lecoeur, C.; Prins, B.P.; Nicolas, A.; Yanek, L.R.; Chen, G.; Jensen, R.A.; Tajuddin, S.; Kabagambe, E.K.; An, P.; Xiang, A.H.; Choi, H.S.; Cade, B.E.; Tan, J.; Flanagan, J.; Abaitua, F.; Adair, L.S.; Adeyemo, A.; Aguilar-Salinas, C.A.; Akiyama, M.; Anand, S.S.; Bertoni, A.; Bian, Z.; Bork-Jensen, J.; Brandslund, I.; Brody, J.A.; Brummett, C.M.; Buchanan, T.A.; Canouil, M.; Chan, J.C.N.; Chang, L.C.; Chee, M.L.; Chen, J.; Chen, S.H.; Chen, Y.T.; Chen, Z.; Chuang, L.M.; Cushman, M.; Das, S.K.; de Silva, H.J.; Dedoussis, G.; Dimitrov, L.; Doumatey, A.P.; Du, S.; Duan, Q.; Eckardt, K.U.; Emery, L.S.; Evans, D.S.; Evans, M.K.; Fischer, K.; Floyd, J.S.; Ford, I.; Fornage, M.; Franco, O.H.; Frayling, T.M.; Freedman, B.I.; Fuchsberger, C.; Genter, P.; Gerstein, H.C.; Giedraitis, V.; Villalpando, C.G.; Villalpando, M.E.G.; Goodarzi, M.O.; Larsen, P.G.; Gorkin, D.; Gross, M.; Guo, Y.; Hackinger, S.; Han, S.; Hattersley, A.T.; Herder, C.; Howard, A.G.; Hsueh, W.; Huang, M.; Huang, W.; Hung, Y.; Hwang, M.Y.; Hwu, C.; Ichihara, S.; Ikram, M.A.; Ingelsson, M.; Islam, M.T.; Isono, M.; Jang, H.M.; Jasmine, F.; Jiang, G.; Jonas, J.B.; Jørgensen, M.E.; Jørgensen, T.; Kamatani, Y.; Kandeel, F.R.; Kasturiratne, A.; Katsuya, T.; Kaur, V.; Kawaguchi, T.; Keaton, J.M.; Kho, A.N.; Khor, C.C.; Kibriya, M.G.; Kim, D.H.; Kohara, K.; Kriebel, J.; Kronenberg, F.; Kuusisto, J.; Läll, K.; Lange, L.A.; Lee, M.; Lee, N.R.; Leong, A.; Li, L.; Li, Y.; Li-Gao, R.; Ligthart, S.; Lindgren, C.M.; Linneberg, A.; Liu, C.; Liu, J.; Locke, A.E.; Louie, T.; Luan, J.; Luk, A.O.; Luo, X.; Lv, J.; Lyssenko, V.; Mamakou, V.; Mani, K.R.; Meitinger, T.; Metspalu, A.; Morris, A.D.; Nadkarni, G.N.; Nadler, J.L.; Nalls, M.A.; Nayak, U.; Nongmaithem, S.S.; Ntalla, I.; Okada, Y.; Orozco, L.; Patel, S.R.; Pereira, M.A.; Peters, A.; Pirie, F.J.; Porneala, B.; Prasad, G.; Preissl, S.; Rasmussen-Torvik, L.J.; Reiner, A.P.; Roden, M.; Rohde, R.; Roll, K.; Sabanayagam, C.; Sander, M.; Sandow, K.; Sattar, N.; Schönherr, S.; Schurmann, C.; Shahriar, M.; Shi, J.; Shin, D.M.; Shriner, D.; Smith, J.A.; So, W.Y.; Stančáková, A.; Stilp, A.M.; Strauch, K.; Suzuki, K.; Takahashi, A.; Taylor, K.D.; Thorand, B.; Thorleifsson, G.; Thorsteinsdottir, U.; Tomlinson, B.; Torres, J.M.; Tsai, F.; Tuomilehto, J.; Tusie-Luna, T.; Udler, M.S.; Salgado, A.V.; Dam, R.M.; Klinken, J.B.; Varma, R.; Vujkovic, M.; Wacher-Rodarte, N.; Wheeler, E.; Whitsel, E.A.; Wickremasinghe, A.R.; Dijk, K.W.; Witte, D.R.; Yajnik, C.S; Yamamoto, K.; Yamauchi, T.; Yengo, L.; Yoon, K.; Yu, C.; Yuan, J.M.; Yusuf, S.; Zhang, L.; Zheng, W.; FinnGen; eMERGE Consortium; Leslie J Raffel; Igase, M.; Ipp, E.; Redline, S.; Cho, Y.S.; Lind, L.; Province, M.A.; Hanis, C.L.; Peyser, P.A.; Ingelsson, E.; Zonderman, A.B.; Psaty, B.M.; Wang, Y.; Rotimi, C.N.; Becker, D.M.; Matsuda, F.; Liu, Y.; Zeggini, E.; Yokota, M.; Rich, S.S.; Kooperberg, C.; Pankow, J.S.; Engert, J.C.; Chen, Y.I.; Froguel, P.; Wilson, J.G.; Sheu, W.H.H.; Kardia, S.L.R.; Wu, J.Y.; Hayes, M.G.; Ma, R.C.W.; Wong, T.Y.; Groop, L.; Mook-Kanamori, D.O.; Chandak, G.R.; Collins, F.S.; Bharadwaj, D.; Paré, G.; Sale, M.M.; Ahsan, H.; Motala, A.A.; Shu, X.O.; Park, K.S.; Jukema, J.W.; Cruz, M.; Cowdin, R.M.; Grallert, H.; Cheng, C.Y.; Bottinger, E.P.; Dehghan, A.; Tai, E.S.; Dupuis, J.; Kato, N.; Laakso, M.; Köttgen, A.; Koh, W.P.; Palmer, C.N.A.; Liu, S.; Abecasis, G.; Kooner, J.S.; Loos, R.J.F.; North, K.E.; Haiman, C.A.; Florez, J.C.; Saleheen, D.; Hansen, T.; Pedersen, O.; Mägi, R.; Langenberg, C.; Wareham, N.J.; Maeda, S.; Kadowaki, T.; Lee, J.; Millwood, I.Y.; Walters, R.G.; Stefansson, K.; Myers, S.R.; Ferrer, J.; Gaulton, K.J.; Meigs, J.B.; Mohlke, K.L.; Gloyn, A.L.; Bowden, D.W.; Below, J.E.; Chambers, J.C.; Sim, X.; Boehnke, M.; Rotter, J.I.; McCarthy, M.I.; Morris, A.P.We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.Item Gastroenterology Update(Gastroenterological and Digestive Endoscopy Society Sri Lanka Colombo, Sri Lanka, 1993) Goonaratna, C.; de Silva, H.J.No abstract availableItem Emerging IBD demographics, phenotype and treatment in South Asia, South-East Asia and Middle East: preliminary findings from the IBD-Emerging Nations' Consortium(Blackwell Scientific Publications, 2022) Banerjee, R.; Pal, P.; Hilmi, I.; Ghoshal, U.C.; Desai, D.C.; Rahman, M.M.; Dutta, U.; Mohiuddin, S.A.; Al Mohannadi, M.; Philip, M.; Ramesh, G.N.; Niriella, M.A.; de Silva, A.P.; de Silva, H.J.; Pisespongsa, P.; Limsrivilai, J.; Aniwan, S.; Nawarathne, M.; Fernandopulle, N.; Aye, T.T.; Ni, N.; Al Awadhi, S.; Joshi, N.; Ngoc, P.T.V.; Kieu, T.V.; Nguyen, A.D.; Abdullah, M.; Ali, E.; Zeid, A.; Sollano, J.D.; Saberi, B.; Omar, M.; Mohsin, M.N.; Aftab, H.; Wai, T.M.; Shastri, Y.M.; Chaudhuri, S.; Ahmed, F.; Bhatia, S.J.; Travis, S.P.L.Abstract Background and aims Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South East Asia and the Middle East, yet epidemiological data are scarce. Methods: We performed a cross-sectional study of IBD demographics, disease phenotype and treatment across 38 centers in 15 countries of South Asia, South-East Asia and Middle East. Intergroup comparisons included gross national income (GNI) per capita. Results: Among 10,400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD-Unclassified 227, 58% male). Peak age of onset was in the third decade, with a low proportion of elderly onset IBD (5% age >60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; IQR 5-30). Treatment of CD included mesalamine, steroids and immunomodulator (61%, 51% and 56% respectively), but a fifth received empirical anti-tubercular therapy. Treatment with biologics was uncommon (4% UC,13% CD) which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD)/100 patient/years. Conclusions: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population-based. UC is twice as common as CD, familial disease uncommon and rates of surgery are low. Biologic use correlates with per capita GNI.Item Side effects of drugs annual(Elsevier, 2001) de Silva, H.J.This chapter presents an overview and discusses the effects of various antiemetics. These drugs include cisapride, clebopride, domperidone, and 5-HT3 receptor antagonists. Clebopride can cause extrapyramidal syndromes, ranging from transient dyskinesia to persistent parkinsonism and tardive dykinesia. The efficacy and adverse effects of domperidone and metoclopramide have been compared in a double-blind, multicenter, randomized trial in 93 insulin-dependent diabetics with symptomatic gastroparesis. The safety and efficacy of the selective 5-HT3 receptor antagonist alosetron in the treatment of irritable bowel syndrome is reviewed. In patients with irritable bowel syndrome, alosetron increases colonic transit time and colonic compliance. Constipation is the most common adverse effect. Several histamine H2 receptor antagonists, such as like cimetidine, and ranitidine are discussed. The drug interactions associated with cimetidine are explained. Cimetidine can interact with other drugs by inhibiting hepatic cytochrome P450.Item Side effects of drugs annual(Elsevier, 1999) de Silva, H.J.This chapter describes the adverse effects of gastrointestinal drugs. The adverse effects of cisapride include abdominal cramps, diarrhea, headache, dystonic reactions, convulsions, and hypersensitivity. Cisapride cardiotoxicity in association with erythromycin is described in the chapter. Cisapride should be used with caution in patients with severe cardiac disease or other risk factors for developing dysrhythmias, particularly hypokalemia and hypomagnesemia. It should not be given to patients with intestinal obstruction, perforation, or hemorrhage. In adults, metoclopramide has been reported to cause gynecomastia and galactorrhea due to hyperprolactinemia secondary to its dopamine antagonist action. Adverse effects attributable to antiemetic therapy include facial rash, constipation, headache, and weakness. The increased risk of acute liver injury with cimetidine is seen mainly in the first two months of use. In a study discussed in the chapter, gynecomastia and a lobular carcinoma of the breast were reported in a patient with chronic gastric ulcer. The hematological adverse effects of ranitidine include leukopenia, thrombocytopenia, aplastic anemia, hemolytic anemia, and pancytopenia.