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On February 23, 2018, PubMed Central Canada (PMC Canada) will be taken offline permanently. No author manuscripts will be deleted, and the approximately 2,900 manuscripts authored by Canadian Institutes of Health Research (CIHR)-funded researchers currently in the archive will be copied to the National Research Council’s (NRC) Digital Repository over the coming months. These manuscripts along with all other content will also remain publicly searchable on PubMed Central (US) and Europe PubMed Central, meaning such manuscripts will continue to be compliant with the Tri-Agency Open Access Policy on Publications.

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1.  Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: management 
Intestinal Research  2018;16(1):17-25.
Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
PMCID: PMC5797267
Tuberculosis; Anti-tumor necrosis factor; Inflammatory bowel disease; Consensus statement
2.  Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment 
Intestinal Research  2018;16(1):4-16.
Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
PMCID: PMC5797269
Tuberculosis; Anti-tumor necrosis factor; Inflammatory bowel disease; Consensus statement
3.  Standing beat-to-beat blood pressure variability is reduced among fallers in the Malaysian Elders Longitudinal Study 
Medicine  2017;96(42):e8193.
The aim of this study was to determine the relationship between falls and beat-to-beat blood pressure (BP) variability.
Continuous noninvasive BP measurement is as accurate as invasive techniques. We evaluated beat-to-beat supine and standing BP variability (BPV) using time and frequency domain analysis from noninvasive continuous BP recordings.
A total of 1218 older adults were selected. Continuous BP recordings obtained were analyzed to determine standard deviation (SD) and root mean square of real variability (RMSRV) for time domain BPV and fast-Fourier transform low frequency (LF), high frequency (HF), total power spectral density (PSD), and LF:HF ratio for frequency domain BPV.
Comparisons were performed between 256 (21%) individuals with at least 1 fall in the past 12 months and nonfallers. Fallers were significantly older (P = .007), more likely to be female (P = .006), and required a longer time to complete the Timed-Up and Go test (TUG) and frailty walk test (P ≤ .001). Standing systolic BPV (SBPV) was significantly lower in fallers compared to nonfallers (SBPV-SD, P = .016; SBPV-RMSRV, P = .033; SBPV-LF, P = .003; SBPV-total PSD, P = .012). Nonfallers had significantly higher supine to standing ratio (SSR) for SBPV-SD, SBPV-RMSRV, and SBPV-total PSD (P = .017, P = .013, and P = .009). In multivariate analyses, standing BPV remained significantly lower in fallers compared to nonfallers after adjustment for age, sex, diabetes, frailty walk, and supine systolic BP. The reduction in frequency-domain SSR among fallers was attenuated by supine systolic BP, TUG, and frailty walk.
In conclusion, reduced beat-to-beat BPV while standing is independently associated with increased risk of falls. Changes between supine and standing BPV are confounded by supine BP and walking speed.
PMCID: PMC5662369  PMID: 29049203
Accidental falls; aged; blood pressure; blood pressure variability; noninvasive monitoring
4.  Disease Burden of Clostridium difficile Infections in Adults, Hong Kong, China, 2006–2014 
Emerging Infectious Diseases  2017;23(10):1671-1679.
Cross-sectional studies suggest an increasing trend in incidence and relatively low recurrence rates of Clostridium difficile infections in Asia than in Europe and North America. The temporal trend of C. difficile infection in Asia is not completely understood. We conducted a territory-wide population-based observational study to investigate the burden and clinical outcomes in Hong Kong, China, over a 9-year period. A total of 15,753 cases were identified, including 14,402 (91.4%) healthcare-associated cases and 817 (5.1%) community-associated cases. After adjustment for diagnostic test, we found that incidence increased from 15.41 cases/100,000 persons in 2006 to 36.31 cases/100,000 persons in 2014, an annual increase of 26%. This increase was associated with elderly patients, for whom incidence increased 3-fold over the period. Recurrence at 60 days increased from 5.7% in 2006 to 9.1% in 2014 (p<0.001). Our data suggest the need for further surveillance, especially in Asia, which contains ≈60% of the world’s population.
PMCID: PMC5621553  PMID: 28930010
Clostridium difficile; bacteria; infections; pseudomembranous colitis; surveillance; epidemiology; disease burden; enteric infections; Hong Kong; China
5.  Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia 
Gut  2016;66(8):1441-1448.
There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma.
We measured relative abundance of Fusobacterium nucleatum (Fn), Peptostreptococcus anaerobius (Pa) and Parvimonas micra (Pm) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects.
The abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker Fn in patients with advanced adenoma than controls (p=0.022). The marker Fn, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively).
This study identified marker Fn as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.
PMCID: PMC5530471  PMID: 27797940
6.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
PMCID: PMC5498855
7.  Multicenter randomised controlled trial comparing the high definition white light endoscopy and the bright narrow band imaging for colon polyps 
To compare high definition white light endoscopy and bright narrow band imaging for colon polyps’ detection rates.
Patients were randomised to high definition white light endoscopy (HD-WLE) or the bright narrow band imaging (bNBI) during withdrawal of the colonoscope. Polyps identified in either mode were characterised using bNBI with dual focus (bNBI-DF) according to the Sano’s classification. The primary outcome was to compare adenoma detection rates (ADRs) between the two arms. The secondary outcome was to assess the negative predictive value (NPV) in differentiating adenomas from hyperplastic polyps for diminutive rectosigmoid lesions.
A total of 1006 patients were randomised to HD-WLE (n = 511) or bNBI (n = 495). The mean of adenoma per patient was 1.62 and 1.84, respectively. The ADRs in bNBI and HD-WLE group were 37.4% and 39.3%, respectively. When adjusted for withdrawal time (OR = 1.19, 95%CI: 1.15-1.24, P < 0.001), the use of bNBI was associated with a reduced ADR (OR = 0.69, 95%CI: 0.52-0.92). Nine hundred and thirty three polyps (86%) in both arms were predicted with high confidence. The sensitivity (Sn), specificity (Sp), positive predictive value and NPV in differentiating adenomatous from non-adenomatous polyps of all sizes were 95.9%, 87.2%, 94.0% and 91.1% respectively. The NPV in differentiating an adenoma from hyperplastic polyp using bNBI-DF for diminutive rectal polyps was 91.0%.
ADRs did not differ between bNBI and HD-WLE, however HD-WLE had higher ADR after adjustment of withdrawal time. bNBI surpassed the PIVI threshold for diminutive polyps.
PMCID: PMC5483420  PMID: 28690771
Narrow band imaging; Dual focus; High definition; White light endoscopy; Colon; Polyps; Randomised controlled trial
8.  Elbow Reconstruction With Compression Plate Arthrodesis and Circumferential Muscle-Sparing Latissimus Dorsi Flap After Tumor Resection 
Hand (New York, N.Y.)  2016;11(1):97-102.
Background: The goals of limb-sparing surgery in the setting of extremity malignancies are 2-fold: oncological clearance and the rehabilitation of function and aesthetics. Treatment success should be defined by the extent of restoration of the patient’s premorbid function for reintegration into society. Methods: We would like to report an unusual case of a patient with a chronically ankylosed elbow with joint invasion by basal cell carcinoma which resulted from malignant transformation of an overlying, long-standing wound due to inadequately treated septic arthritis from his childhood years. Results: Following R0 resection, upper limb shortening and compression plate elbow arthrodesis were performed with the aim of restoring the degree of upper limb function that the patient had been accustomed to preoperatively. The resultant circumferential defect was then closed with a contralateral, free muscle-sparing latissimus dorsi flap. Conclusions: Functional preservation may therefore be more important than the mere restoration of anatomical defects in these especially challenging situations.
PMCID: PMC4920508  PMID: 27418897
upper extremity; limb salvage; elbow; arthrodesis; free flap
9.  Metabolic engineering of Pichia pastoris to produce ricinoleic acid, a hydroxy fatty acid of industrial importance[S] 
Journal of Lipid Research  2015;56(11):2102-2109.
Ricinoleic acid (12-hydroxyoctadec-cis-9-enoic acid) has many specialized uses in bioproduct industries, while castor bean is currently the only commercial source for the fatty acid. This report describes metabolic engineering of a microbial system (Pichia pastoris) to produce ricinoleic acid using a “push” (synthesis) and “pull” (assembly) strategy. CpFAH, a fatty acid hydroxylase from Claviceps purpurea, was used for synthesis of ricinoleic acid, and CpDGAT1, a diacylglycerol acyl transferase for the triacylglycerol synthesis from the same species, was used for assembly of the fatty acid. Coexpression of CpFAH and CpDGAT1 produced higher lipid contents and ricinoleic acid levels than expression of CpFAH alone. Coexpression in a mutant haploid strain defective in the Δ12 desaturase activity resulted in a higher level of ricinoleic acid than that in the diploid strain. Intriguingly, the ricinoleic acid produced was mainly distributed in the neutral lipid fractions, particularly the free fatty acid form, but with little in the polar lipids. This work demonstrates the effectiveness of the metabolic engineering strategy and excellent capacity of the microbial system for production of ricinoleic acid as an alternative to plant sources for industrial uses.
PMCID: PMC4617397  PMID: 26323290
Claviceps purpurea ; fatty acid hydroxylase; diacylglycerol acyltransferase
10.  Physicochemical properties of Malaysian-grown tropical almond nuts (Terminalia catappa) 
Journal of Food Science and Technology  2015;52(10):6623-6630.
The seeds of Terminalia catappa from Malaysia were analyzed for their physicochemical properties. The following values were obtained: moisture 6.23 ± 0.09 %, ash 3.78 ± 0.04 %, lipid 54.68 ± 0.14 %, protein 17.66 ± 0.13 %, total dietary fibre 9.97 ± 0.08 %, carbohydrate 7.68 ± 0.06 %, reducing sugar 1.36 ± 0.16 %, starch 1.22 ± 0.15 %, caloric value 593.48 ± 0.24 %. Studies were also conducted on amino acid profile and free fatty acid composition of the seed oil. Results revealed that glutamic acid was the major essential amino acid while methionine and lysine were the limiting amino acids. The major saturated fatty acid was palmitic acid, while the main unsaturated fatty acid was oleic acid followed by linoleic acid. In addition, the seed was rich in sucrose and had trace amount of glucose and fructose. Briefly, the seed was high in proteins and lipids which are beneficial to human.
PMCID: PMC4573105  PMID: 26396409
Physicochemical properties; Amino acid; Fatty acid characteristics; Terminalia catappa
11.  Surgical management of inflammatory bowel disease in China: a systematic review of two decades 
Intestinal Research  2016;14(4):322-332.
The past decades have seen increasing incidence and prevalence of inflammatory bowel disease (IBD) in China. This article aimed to summarize the current status and characteristics of surgical management for IBD in China.
We searched PubMed, Embase, and Chinese databases from January 1, 1990 to July 1, 2014 for all relevant studies on the surgical treatment IBD in China. Eligible studies with sufficient defined variables were further reviewed for primary and secondary outcome measures.
A total of 74 studies comprising 2,007 subjects with Crohn's disease (CD) and 1,085 subjects with ulcerative colitis (UC) were included. The percentage of CD patients misdiagnosed before surgery, including misdiagnosis as appendicitis or UC, was 50.8%±30.9% (578/1,268). The overall postoperative complication rate was 22.3%±13.0% (267/1,501). For studies of UC, the overall postoperative complication rate was 22.2%±27.9% (176/725). In large research centers (n>50 surgical cases), the rates of emergency operations for CD (P=0.032) and in-hospital mortalities resulting from both CD and UC were much lower than those in smaller research centers (n≤50 surgical cases) (P=0.026 and P <0.001, respectively). Regarding the changes in CD and UC surgery over time, postoperative complications (P=0.045 for CD; P=0.020 for UC) and postoperative in-hospital mortality (P=0.0002 for CD; P=0.0160 for UC) both significantly improved after the year 2010.
The surgical management of IBD in China has improved over time. However, the rates of misdiagnosis and postoperative complications over the past two decades have remained high. Large research centers were found to have relatively better capacity for surgical management than the smaller ones. Higher quality prospective studies are needed in China.
PMCID: PMC5083261  PMID: 27799883
Inflammatory bowel disease; General surgery; China; Systematic review
12.  Carbonic anhydrase IV inhibits colon cancer development by inhibiting the Wnt signalling pathway through targeting the WTAP–WT1–TBL1 axis 
Gut  2015;65(9):1482-1493.
We found that carbonic anhydrase IV (CA4), a member of the carbonic anhydrases, is silenced in colorectal cancer (CRC). We analysed its epigenetic inactivation, biological effects and prognostic significance in CRC.
The biological functions of CA4 were determined by in vitro and in vivo tumorigenicity assays. The CA4 co-operator was identified by immunoprecipitation and mass spectrometry. CA4 downstream effectors and signalling pathways were elucidated by promoter luciferase assay, electrophoretic mobility shift assay and chromatin immunoprecipitation. The clinical impact of CA4 was assessed in 115 patients with CRC.
CA4 was silenced in all nine CRC cell lines and 92.6% of CRC tumours. The promoter hypermethylation contributed to the inactivation of CA4, and it was detected in 75.7% of the patients with CRC. After a median follow-up of 49.3 months, multivariate analysis showed that the patients with CA4 hypermethylation had a recurrence of Stage II/III CRC. The re-expression of CA4 inhibited cell proliferation, induced apoptosis and cell cycle arrest in the G1 phase. CA4 inhibited the activity of the Wnt signalling pathway and mediated the degradation of β-catenin. CA4 interacted with Wilms’ tumour 1-associating protein (WTAP) and induced WTAP protein degradation through polyubiquitination. Moreover, CA4 promoted the transcriptional activity of Wilms’ tumour 1 (WT1), an antagonist of the Wnt pathway, which resulted in the induction of transducin β-like protein 1 (TBL1) and the degradation of β-catenin.
CA4 is a novel tumour suppressor in CRC through the inhibition of the Wnt signalling pathway by targeting the WTAP–WT1–TBL1 axis. CA4 methylation may serve as an independent biomarker for the recurrence of CRC.
PMCID: PMC5036249  PMID: 26071132
13.  Prevalence of hepatitis B and clinical outcomes in inflammatory bowel disease patients in a viral-endemic region 
BMC Gastroenterology  2016;16(1):100.
Little is known of the prevalence of hepatitis B virus (HBV) infection and its effect on choice of therapy and disease course in patients with inflammatory bowel disease (IBD). We assessed the prevalence of HBV in Hong Kong as well as determinants of altered transaminases, effects of HBV infection on therapeutic strategy and clinical course in IBD.
In this retrospective cohort, hepatitis B surface antigen (HBsAg), liver function tests, and IBD disease characteristics were recorded. Logistic regression was used to identify factors associated with altered transaminases.
Four hundred six IBD patients were recruited. HBV infection was found in 5.7 % patients in Hong Kong. The use of steroids (OR, 2.52; p = 0.010) and a previous history of surgery (OR 2.33; p = 0.026) were associated with altered transaminases in IBD. There was no significant difference in disease control and use of IBD medication between HBsAg-positive and HBsAg-negative IBD patients.
The prevalence of HBV among patients with IBD in Hong Kong (5.7 %) is similar to that of general population (~7 %). There was no difference in disease control and use of IBD medication between subjects with or without HBV.
PMCID: PMC4994386  PMID: 27549153
Inflammatory bowel disease; Hepatitis B; Immunosuppression
14.  A Robust Speaker Identification System Using the Responses from a Model of the Auditory Periphery 
PLoS ONE  2016;11(7):e0158520.
Speaker identification under noisy conditions is one of the challenging topics in the field of speech processing applications. Motivated by the fact that the neural responses are robust against noise, this paper proposes a new speaker identification system using 2-D neurograms constructed from the responses of a physiologically-based computational model of the auditory periphery. The responses of auditory-nerve fibers for a wide range of characteristic frequency were simulated to speech signals to construct neurograms. The neurogram coefficients were trained using the well-known Gaussian mixture model-universal background model classification technique to generate an identity model for each speaker. In this study, three text-independent and one text-dependent speaker databases were employed to test the identification performance of the proposed method. Also, the robustness of the proposed method was investigated using speech signals distorted by three types of noise such as the white Gaussian, pink, and street noises with different signal-to-noise ratios. The identification results of the proposed neural-response-based method were compared to the performances of the traditional speaker identification methods using features such as the Mel-frequency cepstral coefficients, Gamma-tone frequency cepstral coefficients and frequency domain linear prediction. Although the classification accuracy achieved by the proposed method was comparable to the performance of those traditional techniques in quiet, the new feature was found to provide lower error rates of classification under noisy environments.
PMCID: PMC4938550  PMID: 27392046
15.  Low-dose azathioprine is effective in maintaining remission in steroid-dependent ulcerative colitis: results from a territory-wide Chinese population-based IBD registry 
Whether low-dose azathioprine (AZA) is effective in maintaining remission in patients with steroid-dependent ulcerative colitis (UC) remains unclear. We assessed the efficacy and safety of low-dose AZA in a Chinese population with UC.
We identified steroid-dependent UC patients in clinical remission on AZA maintenance therapy from a territory-wide IBD Registry. Standard- and low-dose AZA were defined as at least 2 mg/kg/day and less than 2 mg/kg/day, respectively. Relapse rates were analyzed by Kaplan–Meier analysis and compared using log-rank test.
Among 1226 UC patients, 128 (53% male, median duration on AZA 44 months) were included. Median maintenance AZA dose was 1.3 mg/kg/day. 97.7% of the patients were on concomitant oral 5-aminosalicylic acid. Cumulative relapse-free rates in patients on standard-dose and low-dose AZA were 71.2%, 52.8% and 45.2%, and 71.8%, 55.3% and 46.2% at 12, 24 and 36 months, respectively (p = 0.871). Relapse rate within 12 months was higher in patients who withdrew compared with those who maintained on AZA (52.6% versus 29.4%; p = 0.045). Mean corpuscular volume increased after AZA therapy in both of the low-dose [median (interquartile range, IQR): 88.2 (81.4–92.2) versus 95.1 (90.1–100.9) fl, p < 0.001] and standard-dose subgroups [median (IQR) 86.8 (76.9–89.9) versus 94.7 (85.9–99.7) fl, p < 0.001]. Leukopenia occurred in 21.1% of the patients. Patients on standard dose had a higher risk for leukopenia than those on low-dose AZA [odds ratio (OR) 3.9, 95% CI 1.9–8.2, p < 0.001].
In the Chinese population, low-dose AZA is effective for maintaining remission in steroid-dependent UC patients. Standard-dose AZA was associated with more than threefold increased risk of leukopenia.
PMCID: PMC4913336  PMID: 27366213
azathioprine; low dose; steroid-dependent ulcerative colitis
16.  Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations 
Nature genetics  2015;47(9):979-986.
Ulcerative colitis and Crohn’s disease are the two main forms of inflammatory bowel disease (IBD). Here, we report the first trans-ethnic association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East-Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of IBD risk loci, the direction and magnitude of effect is consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by a combination of differences in allele frequencies (NOD2), effect sizes (TNFSF15, ATG16L1) or a combination of both (IL23R, IRGM). Our results provide biological insights into the pathogenesis of IBD, and demonstrate the utility of trans-ethnic association studies for mapping complex disease loci and understanding genetic architecture across diverse populations.
PMCID: PMC4881818  PMID: 26192919
17.  Evaluation of Two New Indices of Blood Pressure Variability Using Postural Change in Older Fallers 
Medicine  2016;95(19):e3614.
To evaluate the utility of blood pressure variability (BPV) calculated using previously published and newly introduced indices using the variables falls and age as comparators.
While postural hypotension has long been considered a risk factor for falls, there is currently no documented evidence on the relationship between BPV and falls.
A case-controlled study involving 25 fallers and 25 nonfallers was conducted. Systolic (SBPV) and diastolic blood pressure variability (DBPV) were assessed using 5 indices: standard deviation (SD), standard deviation of most stable continuous 120 beats (staSD), average real variability (ARV), root mean square of real variability (RMSRV), and standard deviation of real variability (SDRV). Continuous beat-to-beat blood pressure was recorded during 10 minutes’ supine rest and 3 minutes’ standing.
Standing SBPV was significantly higher than supine SBPV using 4 indices in both groups. The standing-to-supine-BPV ratio (SSR) was then computed for each subject (staSD, ARV, RMSRV, and SDRV). Standing-to-supine ratio for SBPV was significantly higher among fallers compared to nonfallers using RMSRV and SDRV (P = 0.034 and P = 0.025). Using linear discriminant analysis (LDA), 3 indices (ARV, RMSRV, and SDRV) of SSR SBPV provided accuracies of 61.6%, 61.2%, and 60.0% for the prediction of falls which is comparable with timed-up and go (TUG), 64.4%.
This study suggests that SSR SBPV using RMSRV and SDRV is a potential predictor for falls among older patients, and deserves further evaluation in larger prospective studies.
PMCID: PMC4902512  PMID: 27175670
18.  Changing epidemiological trends of inflammatory bowel disease in Asia 
Intestinal Research  2016;14(2):111-119.
Inflammatory bowel disease (IBD) has become more common in Asia over the past few decades. The rate of increase in prevalence of the disease varies greatly in Asia, with several countries in East Asia experiencing a more than doubled increase in IBD prevalence over the past decade. Historically, ulcerative colitis (UC) is more common than Crohn's disease (CD) in Asia. However, a reverse trend is beginning to appear in more developed countries in Asia such as Japan, Korea, and Hong Kong. While Asian IBD patients share many similarities with their Western counterparts, there are important differences with significant clinical implications. In Asia, there are more men with CD, more ileo-colonic involvement in CD, less familial aggregation, fewer extra-intestinal manifestations and worse clinical outcomes for older-onset patients with UC. These differences are likely related to the different genetic makeup and environmental exposures in different regions. Evaluation of the differences and rates in epidemiologic trends may help researchers and clinicians estimate disease burden and understand the reasons behind these differences, which may hold the key to unravel the etiology of IBD.
PMCID: PMC4863044  PMID: 27175111
Inflammatory bowel diseases; Colitis, ulcerative; Crohn disease; Asia; Epidemiology
19.  Pro-inflammatory miR-223 mediates the cross-talk between the IL23 pathway and the intestinal barrier in inflammatory bowel disease 
Genome Biology  2016;17:58.
The IL23/Th17 pathway is essential for the onset of inflammatory bowel disease (IBD), yet the specific mechanism by which this pathway initiates the disease remains unknown. In this study, we identify the mechanisms that mediate cross-talk between the IL23 pathway and the intestinal barrier in IBD.
The downstream targets of the IL23 pathway were identified by RNA array profiling and confirmed by immunohistochemical staining. The role of miRNAs that interact with IL23 was explored in mice with TNBS-induced colitis. Claudin-8 (CLDN8), a multigene family protein that constitutes the backbone of tight junctions, was identified as a novel target of IL23 in IBD. CLDN8 was significantly downregulated in IBD patients with inflamed colonic mucosa, and in trinitrobenzene sulphonic acid (TNBS) induced colitis in mice. Therapeutic treatment of colitis in mice using an IL23 antibody restored CLDN8 abundance, in parallel with recovery from colitis. In addition, we identify miR-223 as a novel mediator of the crosstalk between the IL23 signal pathway and CLDN8 in the development of IBD. MiR-223 was upregulated in IBD, and its activity was regulated through the IL23 pathway. Antagomir inhibition of miR-223 reactivated CLDN8 and improved a number of signs associated with TNBS-induced colitis in mice.
Our study characterizes a new mechanistic pathway in IBD, in which miR-223 interacts with the IL23 pathway by targeting CLDN8. Strategies designed to disrupt this interaction may provide novel therapeutic agents for the management of IBD.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-016-0901-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4815271  PMID: 27029486
Crohn’s disease; Ulcerative colitis; Interleukin 23; miRNA; Pathway
20.  Colorectal Cancer Screening Based on Age and Gender 
Medicine  2016;95(10):e2739.
Supplemental Digital Content is available in the text
We evaluated whether age- and gender-based colorectal cancer screening is cost-effective.
Recent studies in the United States identified age and gender as 2 important variables predicting advanced proximal neoplasia, and that women aged <60 to 70 years were more suited for sigmoidoscopy screening due to their low risk of proximal neoplasia. Yet, quantitative assessment of the incremental benefits, risks, and cost remains to be performed.
Primary care screening practice (2008–2015).
A Markov modeling was constructed using data from a screening cohort. The following strategies were compared according to the Incremental Cost Effectiveness Ratio (ICER) for 1 life-year saved: flexible sigmoidoscopy (FS) 5 yearly; colonoscopy 10 yearly; FS for each woman at 50- and 55-year old followed by colonoscopy at 60- and 70-year old; FS for each woman at 50-, 55-, 60-, and 65-year old followed by colonoscopy at 70-year old; FS for each woman at 50-, 55-, 60-, 65-, and 70-year old. All male subjects received colonoscopy at 50-, 60-, and 70-year old under strategies 3 to 5.
From a hypothetical population of 100,000 asymptomatic subjects, strategy 2 could save the largest number of life-years (4226 vs 2268 to 3841 by other strategies). When compared with no screening, strategy 5 had the lowest ICER (US$42,515), followed by strategy 3 (US$43,517), strategy 2 (US$43,739), strategy 4 (US$47,710), and strategy 1 (US$56,510). Strategy 2 leads to the highest number of bleeding and perforations, and required a prohibitive number of colonoscopy procedures. Strategy 5 remains the most cost-effective when assessed with a wide range of deterministic sensitivity analyses around the base case.
From the cost effectiveness analysis, FS for women and colonoscopy for men represent an economically favorable screening strategy. These findings could inform physicians and policy-makers in triaging eligible subjects for risk-based screening, especially in countries with limited colonoscopic resources. Future research should study the acceptability, feasibility, and feasibility of this risk-based strategy in different populations.
PMCID: PMC4998853  PMID: 26962772
22.  Validation of a risk prediction score for proximal neoplasia in colorectal cancer screening: a prospective colonoscopy study 
Scientific Reports  2016;6:20396.
This study developed a clinical scoring system to predict the risks of PN among screening participants for colorectal cancer. We recruited 5,789 Chinese asymptomatic screening participants who received colonoscopy in Hong Kong (2008–2014). From random sampling of 2,000 participants, the independent risk factors were evaluated for PN using binary regression analysis. The odds ratios for significant risk factors were used to develop a scoring system, with scores stratified into ‘average risk’ (AR):0–2 and ‘high risk’ (HR):3–5. The other 3,789 subjects formed an independent validation cohort. Each participant received a score calculated based on their risk factors. The performance of the scoring system was evaluated. The proportion of PN in the derivation and validation cohorts was 12.6% and 12.9%, respectively. Based on age, gender, family history, body mass index and self-reported ischaemic heart disease, 85.0% and 15.0% in the validation cohort were classified as AR and HR, respectively. Their prevalence of PN was 12.0% and 18.1%, respectively. Participants in the HR group had 1.51-fold (95% CI = 1.24–1.84, p < 0.001) higher risk of PN than the AR group. The overall c-statistics of the prediction model was 0.71(0.02). The scoring system is useful in predicting the risk of PN to prioritize patients for colonoscopy.
PMCID: PMC4745041  PMID: 26854201
23.  The discriminatory capability of existing scores to predict advanced colorectal neoplasia: a prospective colonoscopy study of 5,899 screening participants 
Scientific Reports  2016;6:20080.
We evaluated the performance of seven existing risk scoring systems in predicting advanced colorectal neoplasia in an asymptomatic Chinese cohort. We prospectively recruited 5,899 Chinese subjects aged 50–70 years in a colonoscopy screening programme(2008–2014). Scoring systems under evaluation included two scoring tools from the US; one each from Spain, Germany, and Poland; the Korean Colorectal Screening(KCS) scores; and the modified Asia Pacific Colorectal Screening(APCS) scores. The c-statistics, sensitivity, specificity, positive predictive values(PPVs), and negative predictive values(NPVs) of these systems were evaluated. The resources required were estimated based on the Number Needed to Screen(NNS) and the Number Needed to Refer for colonoscopy(NNR). Advanced neoplasia was detected in 364 (6.2%) subjects. The German system referred the least proportion of subjects (11.2%) for colonoscopy, whilst the KCS scoring system referred the highest (27.4%). The c-statistics of all systems ranged from 0.56–0.65, with sensitivities ranging from 0.04–0.44 and specificities from 0.74–0.99. The modified APCS scoring system had the highest c-statistics (0.65, 95% C.I. 0.58–0.72). The NNS (12–19) and NNR (5-10) were similar among the scoring systems. The existing scoring systems have variable capability to predict advanced neoplasia among asymptomatic Chinese subjects, and further external validation should be performed.
PMCID: PMC4738273  PMID: 26838178
24.  Determinants of Bowel Preparation Quality and Its Association With Adenoma Detection 
Medicine  2016;95(2):e2251.
The predictors of poor bowel preparation in colorectal cancer screening participants have not been adequately studied, and the association between the quality of bowel preparation and adenoma detection has not been firmly established. This study examined the determinants of poor bowel preparation, and evaluated its relationship with adenoma detection.
We included subjects aged between 50 and 70 years who received colonoscopy between 2008 and 2014 in a colorectal cancer screening program in Hong Kong. The quality of the bowel preparation was assessed by colonoscopists, and the factors associated with poor bowel cleansing were evaluated by a binary logistic regression analysis. A multivariate regression model was constructed to evaluate if poor bowel preparation was associated with detection of colorectal neoplasia.
From 5470 screening participants (average age 57.7 years, SD 4.9), 1891 (34.6%) had poor or fair bowel preparation. The average cecal intubation time was 7.0 minutes (SD 5.4; range 1.22–36.9 minutes) and the average colonoscopy withdrawal time was 10.8 minutes (SD 6.9; range 6.0–107.0 minutes). Among all, 26.5% had colorectal neoplasia and 5.5% had advanced neoplasia. Older age (≥60 years; adjusted odds ratio [AOR] = 1.19–1.38, P = 0.02–0.04), male sex (AOR = 1.38, 95% confidence interval [CI] 1.19–1.60, P < 0.001), and current smoking (AOR = 1.41, 95% CI 1.14–1.75, P = 0.002) were significantly associated with poor/fair bowel preparation. Poorer cleansing resulted in significantly lower detection rate of neoplasia (AOR = 0.35–0.62) and advanced neoplasia (AOR = 0.36–0.50) irrespective of polyp size.
Steps to improve proper procedures of bowel preparation are warranted, especially among subjects at risk of poor bowel preparation. Strategies should be implemented to improve bowel cleansing, which is now demonstrated as a definite quality indicator.
PMCID: PMC4718228  PMID: 26765402
25.  Gut mucosal microbiome across stages of colorectal carcinogenesis 
Nature Communications  2015;6:8727.
Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). Here we catalogue the microbial communities in human gut mucosae at different stages of colorectal tumorigenesis. We analyse the gut mucosal microbiome of 47 paired samples of adenoma and adenoma-adjacent mucosae, 52 paired samples of carcinoma and carcinoma-adjacent mucosae and 61 healthy controls. Probabilistic partitioning of relative abundance profiles reveals that a metacommunity predominated by members of the oral microbiome is primarily associated with CRC. Analysis of paired samples shows differences in community configurations between lesions and the adjacent mucosae. Correlations of bacterial taxa indicate early signs of dysbiosis in adenoma, and co-exclusive relationships are subsequently more common in cancer. We validate these alterations in CRC-associated microbiome by comparison with two previously published data sets. Our results suggest that a taxonomically defined microbial consortium is implicated in the development of CRC.
Changes in gut microbial communities contribute to the development of colorectal cancer. Here, the authors analyse the gut mucosal microbiome of patients and healthy subjects and identify distinct microbial consortia associated with different stages of colorectal cancer tumorigenesis.
PMCID: PMC4640069  PMID: 26515465

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