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1. Improving VTE risk assessment and prophylaxis prescribing rate in medical patients: integrating risk assessment tool into the workflow

Author

Lauren Davies, Hannah Preston, Iain Swan, Simon Dummer, Yuan Ye Beh, Ann Lockman, and Aravindan Veiraiah

Subjects
Medicine (General), R5-920
Abstract

Medical inpatients often have important risk factors for venous thromboembolism (VTE). In our institution, VTE prophylaxis in this group was underused. The main barriers identified were inattention to VTE prophylaxis, competing priorities and lack of confidence in the decision-making. We aimed to improve the rate of VTE prophylaxis use by introducing a paper-based risk assessment tool, with actionable management recommendations within the prescription chart. The rationale was that an assessment tool at the point of prescribing can reduce steps between decision-making and prescribing process, thus promoting confidence and acting as a reminder. A total of 552 prescription charts completed over a period of 29 weeks were examined during the baseline period. In the postintervention period, 871 charts completed over 40 weeks period were examined. The risk assessment tool was completed in 51% of the cases examined in the postintervention period. The introduction of the risk assessment tool was associated with a significant change in the pattern of VTE pharmacological prophylaxis use. The change occurred when the form was made highly visible and enclosed in the prescription chart. The pharmacological prophylaxis use was higher with a completed assessment form than without (mean (SD) 97.5% (7.6%) vs 70.1% (19.4%); p

Published
2020
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2. How does discharge against medical advice affect risk of mortality and unplanned readmission? A retrospective cohort study set in a large UK medical admissions unit

Author

Anand Alagappan, Thomas J G Chambers, Erik Brown, Sheila M Grecian, and Khalida Ann Lockman

Subjects
Medicine
Abstract

Objectives To assess the frequency of discharge against medical advice (DAMA) in a large UK teaching hospital, explore factors which increase the risk of DAMA and identify how DAMA impacts patient risk of mortality and readmission.Design Retrospective cohort study.Setting Large acute teaching hospital in the UK.Patients 36 683 patients discharged from the acute medical unit of a large UK teaching hospital between 1 January 2012 and 31 December 2016.Measurements Patients were censored on 1 January 2021. Mortality and 30-day unplanned readmission rates were assessed. Deprivation, age and sex were taken as covariates.Results 3% of patients discharged against medical advice. These patients were younger (median age (years) (IQR)): planned discharge (PD) 59 (40–77); DAMA 39 (28–51), predominantly of male sex (PD 48%; DAMA 66%) and were of greater social deprivation (in three most deprived quintiles PD 69%; DAMA 84%). DAMA was associated with increased risk of death in patients under the age of 33.3 years (adjusted HR 2.6 (1.2–5.8)) and increased incidence of 30-day readmission (standardised incidence ratio 1.9 (1.5–2.2)).Limitations Readmission to acute hospitals outside of the local health board may have been missed. We were unable to include information regarding comorbidity or severity of presentation.Conclusions These data highlight the vulnerability of younger patients who DAMA, even in a free-at-the-point-of-delivery healthcare setting.

Published
2023
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3. 36-month clinical outcomes of patients with venous thromboembolism

Author

Alexander G.G. Turpie, Alfredo E. Farjat, Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Shinya Goto, Pantep Angchaisuksiri, Gloria Kayani, Renato D. Lopes, Chern-En Chiang, Harry Gibbs, Eric Tse, Peter Verhamme, Hugo ten Cate, Juan Muntaner, Sebastian Schellong, Henri Bounameaux, Paolo Prandoni, Uma Maheshwari, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool-Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera-Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann-Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau-Chung Wu, Cheng Hock Toh, Chevrier Elisa, Chien-Hsun Hsia, Chien-Lung Huang, Chi-Hang Kevin Kwok, Chih-Cheng Wu, Chi-Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret-Gris, Chung Yin Ha, Chun-Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, David - Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs-Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala-Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia-Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye-Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean-Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans-Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho-Young Yhim, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik-Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M. De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer-Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen-Yuan Kuo, Jhih-Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jørn Nielsen, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou-Gi Shyu, Kristel Vandenbosch, Kuan-Cheng Chang, Kuan-Ming Chiu, Kubina Jean-Manuel, Kwan Jing Wern, Kwo-Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool-Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El-Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon-Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan-Keim, Remedios Otero, Renate Murena-Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung-Hyun Nam, Sevestre-Pietri Marie-Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe-Nana Jean-Léopold, Somchai Wongkhantee, Soo-Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel-Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting-Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei-Hsiang Lin, Weihua Zhang, Wei-Kung Tseng, Wen-Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won Il Choi, Yang-Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung-Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Pulmonary Medicine, Clinical Genetics, Internal Medicine, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ACS - Diabetes & metabolism, VU University medical center, Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), and RS: Carim - B04 Clinical thrombosis and Haemostasis

Subjects
History, Anticoagulation, Registry, Polymers and Plastics, SDG 3 - Good Health and Well-being, Deep vein thrombosis, Pulmonary embolism, Hematology, Business and International Management, Industrial and Manufacturing Engineering, Venous thromboembolism
Abstract

BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

Published
2023

5. Long-term outcomes of patients investigated for suspected upper extremities deep venous thrombosis irrespective of imaging results

Author

Chibuzo Jemade, John T. Murchison, Katie Louise McCullough, Caroline Gallacher, Sidra Kosar, Khalida Ann Lockman, Daniel Tze Yee Ang, and Tobias Walter Lombaert Haseler

Subjects
Adult, Venous Thrombosis, medicine.medical_specialty, business.industry, Hazard ratio, Cancer, General Medicine, medicine.disease, Thrombosis, Education, Upper Extremity, Venous thrombosis, Risk Factors, Cohort, medicine, Humans, Radiology, Prospective Studies, Thrombus, Prospective cohort study, business, Cause of death, Retrospective Studies
Abstract

Background Outcome data are limited for upper extremity deep venous thrombosis (UEDVT). The outcomes of patients investigated for, but without UEDVT remain uncertain. Methods Retrospective analysis of clinical records of adult patients undergoing Doppler ultrasound for potential UEDVT between 1 January 2007 and 31 December 2014 was undertaken. Primary outcome was all-cause mortality. Secondary outcomes were new cancer diagnosis and thromboembolic recurrence. Results The final cohort (n = 528) comprised 25 primary UEDVT, 100 secondary UEDVT, 40 superficial-venous thrombosis and 363 without thrombus patients. There were 207 deaths. Survival was higher in primary than in secondary UEDVT (log-rank p < 0.0001) or those without thrombus (log-rank p = 0.001). Pre-existing cancer [hazard ratio 3.6 (95% confidence interval 1.5-8.9)] was the biggest independent predictor of mortality and leading cause of death. Developing UEDVT was a poor prognostic marker in cancer patients. Conclusion There was high early mortality regardless of radiological findings, with the exception of primary UEDVT. Prospective studies evaluating aggressive treatment of underlying comorbidities in these patients are needed.

Published
2020

6. Improving VTE risk assessment and prophylaxis prescribing rate in medical patients: integrating risk assessment tool into the workflow

Author

Simon Dummer, Hannah Preston, Iain Swan, Veiraiah Aravindan, Ann Lockman, Lauren Davies, and Yuan Ye Beh

Subjects
medicine.medical_specialty, Quality management, Leadership and Management, Quality Improvement Report, venous thromboembolism, Risk management tools, 030204 cardiovascular system & hematology, Drug Prescriptions, Risk Assessment, quality improvement, Workflow, 03 medical and health sciences, Patient safety, 0302 clinical medicine, Chart, Risk Factors, patient safety, Medicine, Humans, Medical prescription, lcsh:R5-920, business.industry, Health Policy, Public Health, Environmental and Occupational Health, Anticoagulants, medication safety, 030228 respiratory system, Emergency medicine, Guideline Adherence, Risk assessment, business, Pulmonary Embolism, lcsh:Medicine (General), Venous thromboembolism, clinical practice guidelines
Abstract

Medical inpatients often have important risk factors for venous thromboembolism (VTE). In our institution, VTE prophylaxis in this group was underused. The main barriers identified were inattention to VTE prophylaxis, competing priorities and lack of confidence in the decision-making. We aimed to improve the rate of VTE prophylaxis use by introducing a paper-based risk assessment tool, with actionable management recommendations within the prescription chart. The rationale was that an assessment tool at the point of prescribing can reduce steps between decision-making and prescribing process, thus promoting confidence and acting as a reminder. A total of 552 prescription charts completed over a period of 29 weeks were examined during the baseline period. In the postintervention period, 871 charts completed over 40 weeks period were examined. The risk assessment tool was completed in 51% of the cases examined in the postintervention period. The introduction of the risk assessment tool was associated with a significant change in the pattern of VTE pharmacological prophylaxis use. The change occurred when the form was made highly visible and enclosed in the prescription chart. The pharmacological prophylaxis use was higher with a completed assessment form than without (mean (SD) 97.5% (7.6%) vs 70.1% (19.4%); p

Published
2020

7. Anticoagulation therapy patterns for acute treatment of venous thromboembolism in GARFIELD-VTE patients

Author

Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Alexander G.G. Turpie, Shinya Goto, Pantep Angchaisuksiri, Joern Dalsgaard Nielsen, Gloria Kayani, Audrey Zaghdoun, Alfredo E. Farjat, Sebastian Schellong, Henri Bounameaux, Lorenzo G. Mantovani, Paolo Prandoni, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool‐Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera‐Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim, Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann‐Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau‐Chung Wu, Cheng Hock Toh, Chern‐En Chiang, Chevrier Elisa, Chien‐Hsun Hsia, Chien‐Lung Huang, Chi‐Hang Kevin Kwok, Chih‐Cheng Wu, Chi‐Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret‐Gris, Chung Yin Ha, Chun‐Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs‐Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala‐Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia‐Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye‐Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean‐Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans‐Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Harry Gibbs, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho‐Young Yhim, Hugo ten Cate, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik‐Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer‐Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen‐Yuan Kuo, Jhih‐Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou‐Gi Shyu, Kristel Vandenbosch, Kuan‐Cheng Chang, Kuan‐Ming Chiu, Kubina Jean‐Manuel, Kwan Jing Wern, Kwo‐Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool‐Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El‐Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon‐Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Peter Verhamme, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan‐Keim, Remedios Otero, Renate Murena‐Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung‐Hyun Nam, Sevestre‐Pietri Marie‐Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe‐Nana Jean‐Léopold, Somchai Wongkhantee, Soo‐Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel‐Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting‐Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei‐Hsiang Lin, Weihua Zhang, Wei‐Kung Tseng, Wen‐Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won II Choi, Yang‐Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung‐Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Haas, S, Ageno, W, Weitz, J, Goldhaber, S, Turpie, A, Goto, S, Angchaisuksiri, P, Dalsgaard Nielsen, J, Kayani, G, Zaghdoun, A, Farjat, A, Schellong, S, Bounameaux, H, Mantovani, L, Prandoni, P, and Kakkar, A

Subjects
Male, pulmonary embolism, Time Factors, Deep vein, direct oral anticoagulant, Practice Patterns, 030204 cardiovascular system & hematology, heparin, Direct oral anticoagulants, 0302 clinical medicine, Pregnancy, Deep vein thrombosis, 80 and over, Registries, Practice Patterns, Physicians', ddc:616, Aged, 80 and over, Venous Thrombosis, Anticoagulant, Hematology, Heparin, Middle Aged, Thrombosis, Pulmonary embolism, medicine.anatomical_structure, Treatment Outcome, Practice Guidelines as Topic, Female, Guideline Adherence, medicine.drug, medicine.medical_specialty, medicine.drug_class, venous thromboembolism, direct oral anticoagulants, deep vein thrombosis, Aged, Anticoagulants, Blood Coagulation, Drug Utilization, Healthcare Disparities, Humans, Pulmonary Embolism, Venous Thromboembolism, 03 medical and health sciences, Thromboembolism, Internal medicine, medicine, In patient, cardiovascular diseases, Rivaroxaban, Physicians', business.industry, deep vein thrombosi, deep vein thrombosis, direct oral anticoagulants, heparin, pulmonary embolism, venous thromboembolism, equipment and supplies, Venous, medicine.disease, business, Venous thromboembolism
Abstract

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Published
2019

8. Risk of death following admission to a UK hospital with diabetic ketoacidosis

Author

K. Ann Lockman, Wei Leng Teoh, Joanne Graham, and Fraser W. Gibb

Subjects
Adult, Male, medicine.medical_specialty, Diabetic ketoacidosis, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Diabetic Ketoacidosis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, Diabetes mellitus, medicine, Internal Medicine, Humans, 030212 general & internal medicine, Young adult, Intensive care medicine, Retrospective Studies, Glycated Hemoglobin, Type 1 diabetes, business.industry, nutritional and metabolic diseases, Retrospective cohort study, Human physiology, Middle Aged, medicine.disease, United Kingdom, Hospitalization, Diabetes Mellitus, Type 1, Hospital admission, Female, Risk of death, business
Abstract

The aim of this study was to assess the risk of death during hospital admission for diabetic ketoacidosis (DKA) and, subsequently, following discharge. In addition, we aimed to characterise the risk factors for multiple presentations with DKA.We conducted a retrospective cohort study of all DKA admissions between 2007 and 2012 at a university teaching hospital. All patients with type 1 diabetes who were admitted with DKA (628 admissions of 298 individuals) were identified by discharge coding. Clinical, biochemical and mortality data were obtained from electronic patient records and national databases. Follow-up continued until the end of 2014.Compared with patients with a single DKA admission, those with recurrent DKA (more than five episodes) were diagnosed with diabetes at an earlier age (median 14 [interquartile range 9-23] vs 24 [16-34] years, p 0.001), had higher levels of social deprivation (p = 0.005) and higher HbA1c values (103 [89-108] vs 79 [66-96] mmol/mol; 11.6% [10.3-12.0%] vs 9.4% [8.2-10.9%], p 0.001), and tended to be younger (25 [22-36] vs 31 [23-42] years, p = 0.079). Antidepressant use was greater in those with recurrent DKA compared with those with a single episode (47.5% vs 12.6%, p = 0.001). The inpatient DKA mortality rate was no greater than 0.16%. A single episode of DKA was associated with a 5.2% risk of death (4.1 [2.8-6.0] years of follow-up) compared with 23.4% in those with recurrent DKA admissions (2.4 [2.0-3.8] years of follow-up) (HR 6.18, p = 0.001).Recurrent DKA is associated with substantial mortality, particularly among young, socially disadvantaged adults with very high HbA1c levels.

Published
2016

9. Excess long-term mortality in outpatient deep venous thrombosis patients managed in an ambulatory care setting

Author

Johanne M Simpson, Daniel T. Y. Ang, Khalida Ann Lockman, John T. Murchison, and Isaiah C Stewart

Subjects
Adult, Male, medicine.medical_specialty, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, 0302 clinical medicine, Ambulatory care, Internal medicine, Cause of Death, Neoplasms, medicine, Ambulatory Care, Humans, cardiovascular diseases, Cause of death, Aged, Retrospective Studies, Aged, 80 and over, Venous Thrombosis, business.industry, Cancer, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Thrombosis, Surgery, Venous thrombosis, Scotland, 030220 oncology & carcinogenesis, Cohort, Long term mortality, Female, business, Follow-Up Studies
Abstract

Background: Deep venous thrombosis (DVT) is increasingly being managed in the outpatient setting, particularly patients deemed low-risk at presentation. The long-term outcomes of these patients remain unclear. Aim: To determine the long-term outcomes of patients with DVT and those with raised D-dimer without DVT managed exclusively by an ambulatory care pathway. Design: Retrospective cohort analysis. Methods: 828 consecutive patients assessed at the Ambulatory Care Clinic of a tertiary care university hospital between 1 January and 31 December 2008 for potential lower limb DVT were analysed. Primary and secondary outcome was all-cause mortality and new diagnosis of cancer, respectively. Median follow-up was 6.4 years. Results: The final cohort comprised 131 patients with DVT, 396 with raised D-dimer without DVT and 165 with normal D-dimer without DVT. Long-term survival was 72.5% for DVT, 75.3% for elevated D-dimer without thrombosis and 93.3% for those with normal D-dimer ( P < 0.0001). The risk of death with DVT remained significant after adjusting for age, gender, previous cancer, recent surgery and previous thromboembolism (HR 2.17, 95% CI [1.07, 4.38]). Cancer accounted for 44.4 and 37.8% of deaths within the first and second groups, respectively. 50% of cancers in the former group were diagnosed during follow-up vs. 95.1% in the latter. Conclusion: The 5-year survival of patients with DVT managed via ambulatory care was worse than expected. An algorithm is urgently needed to identify predictors of adverse outcomes for both these patients as well as those with raised D-dimer without thrombosis.

Published
2016

10. Interrelationships between Hepatic Fat and Insulin Resistance in Non- Alcoholic Fatty Liver Disease

Author

Khalida Ann Lockman and Moffat J. Nyirenda

Subjects
medicine.medical_specialty, Mitochondrial Diseases, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Disease, Models, Biological, Endocrinology, Insulin resistance, Non-alcoholic Fatty Liver Disease, Diabetes mellitus, Internal medicine, Animals, Humans, Medicine, business.industry, Fatty liver, Non alcoholic, Lipid Metabolism, medicine.disease, Obesity, digestive system diseases, Fatty Liver, Adipose Tissue, Liver, Insulin Resistance, Steatosis, business
Abstract

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance, and its prevalence is rising in parallel with worldwide increases in obesity and type 2 diabetes. However, the nature of this relationship remains debatable. In particular, it is unclear whether insulin resistance causes NAFLD or hepatic steatosis per se reduces insulin sensitivity. This review will examine data from recent studies on the link between insulin resistance and NAFLD, focusing on studies that have attempted to dissociate fatty liver and hepatic insulin resistance.

Published
2010

11. Non-Alcoholic Fatty Liver Disease: Pathogenesis Directed Therapy – the Way Forward

Author

Ann Lockman, Peter C. Hayes, and Norma C. McAvoy

Subjects
medicine.medical_specialty, Cirrhosis, medicine.diagnostic_test, business.industry, Fatty liver, nutritional and metabolic diseases, Hepatitis C, medicine.disease, Gastroenterology, Liver disorder, Liver disease, Internal medicine, medicine, Steatohepatitis, Metabolic syndrome, business, Liver function tests
Abstract

Although fatty liver injury can occur in a number of non-alcoholic settings, such as hepatitis C infection, drug reactions and starvation, the term Non-Alcoholic Fatty Liver Disease (NAFLD) is reserved for the liver disorder that is associated with insulin resistance and the ‘Metabolic Syndrome’ (MS). NAFLD is the rather nondescript term used for the spectrum of liver diseases, incorporating simple steatosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, which histologically resembles alcoholic liver injury in the absence of alcohol abuse. NAFLD has become a common reason for ‘liver referral’ due largely to the practice of measuring liver function tests in patients started on statin therapy and the rising prevalence of obesity in many countries. Despite being such a common problem it is still commonly misdiagnosed, overlooked or ignored. Its importance as a cause of ‘cryptogenic cirrhosis’, a cause of morbidity and mortality particularly in patients with type 2 diabetes mellitus and perhaps as an in...

Published
2007

12. Audit of cardiovascular risk assessment in type 2 diabetic patients referred for insulin therapy: a cardiological perspective

Author

John Chalmers, K Ann Lockman, Ian W Campbell, Peter A Henriksen, Sharon J Robertson, Janet Ip Barclay, and Donna Clark

Subjects
Drug, medicine.medical_specialty, education.field_of_study, Statin, business.industry, medicine.drug_class, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Insulin, medicine.medical_treatment, Population, Audit, medicine.disease, Diabetes mellitus, Internal Medicine, medicine, Medical prescription, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, education, Risk assessment, media_common
Abstract

We present an audit of cardiovascular risk, and drug prescription of 250 type 2 diabetic patients referred from primary care to a District General Hospital for prescription of 250 type 2 diabetic patients referred from primary care to a District General Hospital for management of insulin therapy. Prescription patterns were compared to current UK guidelines for primary and secondary prevention and evidence-based practice. The audit uncovered substantial under-recognition of the high vascular risk of this type 2 diabetic population with respect to the use of antiplatelet therapy, statins and angiotensin blockers. Type 2 diabetic patients requiring insulin therapy have a particularly high cardiovascular risk and we believe they should be considered for antiplatelet, statin and angiotensin blocking therapy on initiation of insulin treatment even if they have no previous history of overt vascular events.

Published
2004

13. Diabetic MRSA foot infection — role of linezolid therapy

Author

Joanna M Turner, K Ann Lockman, Diptendu N Bhattacharyya, Lukman M Hakeem, and Ian W Campbell

Subjects
medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Antibiotics, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Diabetes mellitus, Internal Medicine, medicine, Foot ulcers, Intensive care medicine, business.industry, Public health, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, medicine.disease, chemistry, Amputation, Linezolid, Vancomycin, Cardiology and Cardiovascular Medicine, business, Foot (unit), medicine.drug
Abstract

Diabetic foot ulceration is common and disabling, often leading to amputation of the leg. Foot ulcers commonly become infected and MRSA infection is becoming more prevalent. MRSA is becoming a major public health problem because of its associated high morbidity and mortality, due to difficulty in its eradication with conventional antibiotics. Although vancomycin is the present mainstay of treatment of MRSA infection, a recently introduced antibiotic, linezolid may have benefits. Linezolid can be given orally, obviating the need for i.v. monitoring and offering potential savings in hospital costs with earlier discharge because of its suitability for out-patient eradication of MRSA.

Published
2004

14. Fibrinogen production is enhanced in an in-vitro model of non-alcoholic fatty liver disease: an isolated risk factor for cardiovascular events?

Author

Yeung, Emily N. W., Treskes, Philipp, Martin, Sarah F., Manning, Jonathan R., Dunbar, Donald R., Rogers, Sophie M., Le Bihan, Thierry, Ann Lockman, K., Morley, Steven D., Hayes, Peter C., Nelson, Leonard J., and Plevris, John N.

Abstract

Background: Cardiovascular disease (CVD) remains the major cause of excess mortality in patients with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the individual contribution of NAFLD to CVD risk factors in the absence of pathogenic influences from other comorbidities often found in NAFLD patients, by using an established in-vitro model of hepatic steatosis. Methods: Histopathological events in non-alcoholic fatty liver disease were recapitulated by focused metabolic nutrient overload of hepatoblastoma C3A cells, using oleate-treated-cells and untreated controls for comparison. Microarray and proteomic data from cell culture experiments were integrated into a custom-built systems biology database and proteogenomics analysis performed. Candidate genes with significant dysregulation and concomitant changes in protein abundance were identified and STRING association and enrichment analysis performed to identify putative pathogenic pathways. Results: The search strategy yielded 3 candidate genes that were specifically and significantly up-regulated in nutrient-overloaded cells compared to untreated controls: fibrinogen alpha chain (2.2 fold), fibrinogen beta chain (2.3 fold) and fibrinogen gamma chain (2.1 fold) (all rank products pfp <0.05). Fibrinogen alpha and gamma chain also demonstrated significant concomitant increases in protein abundance (3.8-fold and 2.0-fold, respectively, p <0.05). Conclusions: In-vitro modelling of NAFLD and reactive oxygen species formation in nutrient overloaded C3A cells, in the absence of pathogenic influences from other comorbidities, suggests that NAFLD is an isolated determinant of CVD. Nutrient overload-induced up-regulation of all three fibrinogen component subunits of the coagulation cascade provides a possible mechanism to explain the excess CVD mortality observed in NAFLD patients. [ABSTRACT FROM AUTHOR]

Published
2015
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15. Erratum to: Fibrinogen production is enhanced in an in-vitro model of non-alcoholic fatty liver disease: an isolated risk factor for cardiovascular events?

Author

Emily N. W. Yeung, Philipp Treskes, Sarah F. Martin, Jonathan R. Manning, Donald R. Dunbar, Sophie M. Rogers, Thierry Le Bihan, K. Ann Lockman, Steven D. Morley, Peter C. Hayes, Leonard J. Nelson, and John N. Plevris

Subjects
Proteomics, Biochemistry, medical, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Fibrinogen, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Models, Biological, Up-Regulation, 03 medical and health sciences, Farnesyl-Diphosphate Farnesyltransferase, 0302 clinical medicine, Endocrinology, Cardiovascular Diseases, Non-alcoholic Fatty Liver Disease, Risk Factors, Cell Line, Tumor, Humans, Erratum, Genetic Association Studies, Oligonucleotide Array Sequence Analysis, Signal Transduction
Abstract

Cardiovascular disease (CVD) remains the major cause of excess mortality in patients with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the individual contribution of NAFLD to CVD risk factors in the absence of pathogenic influences from other comorbidities often found in NAFLD patients, by using an established in-vitro model of hepatic steatosis.Histopathological events in non-alcoholic fatty liver disease were recapitulated by focused metabolic nutrient overload of hepatoblastoma C3A cells, using oleate-treated-cells and untreated controls for comparison. Microarray and proteomic data from cell culture experiments were integrated into a custom-built systems biology database and proteogenomics analysis performed. Candidate genes with significant dysregulation and concomitant changes in protein abundance were identified and STRING association and enrichment analysis performed to identify putative pathogenic pathways.The search strategy yielded 3 candidate genes that were specifically and significantly up-regulated in nutrient-overloaded cells compared to untreated controls: fibrinogen alpha chain (2.2 fold), fibrinogen beta chain (2.3 fold) and fibrinogen gamma chain (2.1 fold) (all rank products pfp0.05). Fibrinogen alpha and gamma chain also demonstrated significant concomitant increases in protein abundance (3.8-fold and 2.0-fold, respectively, p0.05).In-vitro modelling of NAFLD and reactive oxygen species formation in nutrient overloaded C3A cells, in the absence of pathogenic influences from other comorbidities, suggests that NAFLD is an isolated determinant of CVD. Nutrient overload-induced up-regulation of all three fibrinogen component subunits of the coagulation cascade provides a possible mechanism to explain the excess CVD mortality observed in NAFLD patients.

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16. P-glycoprotein Mediated Efflux Limits Substrate and Drug Uptake in a Preclinical Brain Metastases of Breast Cancer Model

Author

Chris E Adkins, Rajendar Kumar Mittapalli, Vamshi Krishna Manda, Mohamed Ismail Nounou, Afroz Shareef Mohammad, Tori Breanne Terrrell, Kaci Ann Bohn, Celik eYasemin, Tiffany Renee Grothe, Julie Ann Lockman, and Paul Richard Lockman

Subjects
Autoradiography, Drug Resistance, chemotherapy, tumor, fluorescence microscopy, Therapeutics. Pharmacology, RM1-950
Abstract

The blood-brain barrier (BBB) is a specialized vascular interface that restricts the entry of many compounds into brain. This is accomplished through the sealing of vascular endothelial cells together with tight junction proteins to prevent paracellular diffusion. In addition, the BBB has a high degree of expression of numerous efflux transporters which actively extrude compounds back into blood. However, when a metastatic lesion develops in brain the vasculature is typically compromised with increases in passive permeability (blood-tumor barrier; BTB). What is not well documented is to what degree active efflux retains function at the BTB despite the changes observed in passive permeability. In addition, there have been previous reports documenting both increased and decreased expression of P-gp in lesion vasculature. Herein, we simultaneously administer a passive diffusion marker (14C-AIB) and a tracer subject to P-gp efflux (rhodamine 123) into a murine preclinical model of brain metastases of breast cancer. We observed that the metastatic lesions had similar expression (p>0.05; n=756-1214 vessels evaluated) at the BBB and the BTB. Moreover, tissue distribution of R123 was not significantly (p>0.05) different between normal brain and the metastatic lesion. It is possible that the similar expression of P-gp on the BBB and the BTB contribute to this phenomenon. Additionally we observed P-gp expression at the metastatic cancer cells adjacent to the vasculature which may also contribute to reduced R123 uptake into the lesion. The data suggest that despite the disrupted integrity of the BTB, efflux mechanisms appear to be intact, and may be functionally comparable to the normal BBB. The BTB is a significant hurdle to delivering drugs to brain metastasis.

Published
2013
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