Browsing by Author "Barts and The London NHS Trust"

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    Change in vitamin D levels and risk of severe vitamin D deficiency over 48 weeks among HIV-1-infected, treatment-naive adults receiving rilpivirine or efavirenz in a Phase III trial (ECHO)
    (2014-01-01) David A. Wohl; Chloe Orkin; Manuela Doroana; José H. Pilotto; Somnuek Sungkanuparph; Patrick Yeni; Simon Vanveggel; Henri Deckx; Katia Boven; The University of North Carolina at Chapel Hill; Barts and The London NHS Trust; Santa Maria Hospital, Lisbon; Hospital Geral de Rio de Janeiro; Mahidol University; Hopital Bichat-Claude-Bernard AP-HP; Janssen Infectious Diseases BVBA; Janssen
    Background: This analysis assessed changes in serum 25-hydroxyvitamin D (25[OH]D; the precursor form of active vitamin D) in antiretroviral-naive adults receiving rilpivirine or efavirenz over 48 weeks in a randomized, double-blind, Phase III trial (ECHO). Methods: ECHO included 690 patients randomized 1:1 to receive rilpivirine 25 mg once daily (n=346) or efavirenz 600 mg once daily (n=344), plus tenofovir disoproxil fumarate/emtricitabine. 25(OH)D was measured in stored serum samples collected at baseline, and weeks 24 and 48. Proportions of patients with optimal/sufficient (≥30 ng/ml), insufficient (21-29 ng/ml), deficient (10-20 ng/ml) and severely deficient (<10 ng/ml) 25(OH) D levels were determined. Data are presented for patients with paired baseline and week 48 25(OH)D data (rilpivirine, n=292; efavirenz, n=290). Results: After 48 weeks, mean 25(OH)D levels remained largely unchanged from baseline with rilpivirine (-0.2 ng/ml; P=0.57 versus no change), but were significantly reduced with efavirenz (-2.5 ng/ml; P<0.0001 versus no change). When adjusting for season of randomization and the combined variable of race (Black/African American, White/Caucasian, Asian, other race) and ethnicity (Hispanic or Latino and not Hispanic or not Latino), the conclusion about the treatment difference between the rilpivirine and efavirenz treatment groups remained valid. At baseline the proportion of patients with severe 25(OH)D deficiency was similar in both groups (5%) but was significantly lower with rilpivirine than efavirenz at week 48 (5% versus 9%, respectively; P=0.032). Furthermore, of the patients with 25(OH)D insufficiency/deficiency at baseline, the proportion who developed severe 25(OH)D deficiency at week 48 was significantly lower with rilpivirine than efavirenz (2% versus 8%, respectively; P=0.0079). Conclusions: Rilpivirine had little effect on 25(OH)D, whereas efavirenz resulted in a significant reduction in 25(OH)D levels and an increase in the risk of severe 25(OH)D deficiency. © 2014 International Medical Press 1359-6535.
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    An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid
    (2016-01-01) Vanessa K. Wong; Stephen Baker; Thomas R. Connor; Derek Pickard; Andrew J. Page; Jayshree Dave; Niamh Murphy; Richard Holliman; Armine Sefton; Michael Millar; Zoe A. Dyson; Gordon Dougan; Kathryn E. Holt; Julian Parkhill; Robert A. Kingsley; Nicholas R. Thomson; Jacqueline A. Keane; James Hadfield; Elizabeth J. Klemm; Simon R. Harris; Amy K. Cain; Samuel Kariuki; Chinyere Okoro; Calman A. MacLennan; Nga Tran Vu Thieu; Duy Pham Thanh; Corinne Thompson; Christiane Dolecek; James I. Campbell; Guy Thwaites; Jeremy Farrar; Paul N. Newton; David Dance; Paul Turner; E. Kim Mulholland; Jane Hawkey; David J. Edwards; Nicholas A. Feasey; François Xavier Weill; Simon Le Hello; Peter J. Hart; Robert F. Breiman; Robert S. Onsare; Conall H. Watson; W. John Edmunds; Melita A. Gordon; Robert S. Heyderman; Chisomo Msefula; Jan Jacobs; Octavie Lunguya; Jose A. Chabalgoity; Mike Kama; Kylie Jenkins; Shanta Dutta; Florian Marks; Josefina Campos; Stephen Obaro; Karen H. Keddy; Anthony M. Smith; Christopher M. Parry; Abhilasha Karkey; Sabina Dongol; Buddha Basnyat; Amit Arjyal; Muriel Dufour; Don Bandaranayake; Wellcome Trust Sanger Institute; Addenbrooke's Hospital; UCL; Nuffield Department of Clinical Medicine; London School of Hygiene & Tropical Medicine; Cardiff University; Public Health England; Barts and The London NHS Trust; University of Melbourne; Bio21 Molecular Science and Biotechnology Institute; Liverpool School of Tropical Medicine; Quadram Institute Bioscience; Institut Pasteur, Paris; University of Birmingham; Kenya Medical Research Institute; Centers for Disease Control and Prevention; Emory Global Health Institute; University of Liverpool; University of Malawi College of Medicine; Prins Leopold Instituut voor Tropische Geneeskunde; KU Leuven; National Institute for Biomedical Research; University Hospital of Kinshasa; Universidad de la Republica Instituto de Higiene; Ministry of Health; null; National Institute of Cholera and Enteric Diseases India; International Vaccine Institute, Seoul; ANLIS-Carlos G Malbran Institute; University of Nebraska Medical Center; University of Abuja; Bingham University; University of Witwatersrand; Nagasaki University; Oxford University Clinical Research Unit; Murdoch Children's Research Institute; Institute of Environmental Science and Research Limited (ESR); ESR - Kenepuru Science Centre; Samoa Ministry of Health; Organisation Mondiale de la Sante; Hasanuddin University; Mahosot Hospital; Tupua Tamasese Meaole Hospital; Mahidol University; Chelsea and Westminster Hospital; University of Otago; Angkor Hospital for Children; University of Cambridge; St Augustine's Hospital
    © The Author(s) 2016. The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.
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    Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa
    (2016-09-22) Vanessa K. Wong; Kathryn E. Holt; Chinyere Okoro; Stephen Baker; Derek J. Pickard; Florian Marks; Andrew J. Page; Grace Olanipekun; Huda Munir; Roxanne Alter; Paul D. Fey; Nicholas A. Feasey; François Xavier Weill; Simon Le Hello; Peter J. Hart; Samuel Kariuki; Robert F. Breiman; Melita A. Gordon; Robert S. Heyderman; Jan Jacobs; Octavie Lunguya; Chisomo Msefula; Calman A. MacLennan; Karen H. Keddy; Anthony M. Smith; Robert S. Onsare; Elizabeth De Pinna; Satheesh Nair; Ben Amos; Gordon Dougan; Stephen Obaro; Julian Parkhill; Robert A. Kingsley; Nicholas R. Thomson; Jacqueline A. Keane; Jane Hawkey; David J. Edwards; Zoe A. Dyson; Simon R. Harris; Amy K. Cain; James Hadfield; Elizabeth J. Klemm; Conall H. Watson; W. John Edmunds; Nga Tran Vu Thieu; Mike Kama; Kylie Jenkins; Shanta Dutta; Josefina Campos; Corinne Thompson; Christiane Dolecek; Christopher M. Parry; Abhilasha Karkey; E. Kim Mulholland; James I. Campbell; Sabina Dongol; Buddha Basnyat; Amit Arjyal; Muriel Dufour; Don Bandaranayake; Take N. Toleafoa; Shalini Pravin Singh; Mochammad Hatta; Lupeoletalalelei Isaia; Wellcome Trust Sanger Institute; Addenbrooke's Hospital; Bio21 Molecular Science and Biotechnology Institute; University of Melbourne; UCL; Nuffield Department of Clinical Medicine; London School of Hygiene & Tropical Medicine; International Vaccine Institute, Seoul; International Foundation Against Infectious Diseases in Nigeria (IFAIN); Aminu Kano Teaching Hospital; University of Nebraska Medical Center; Liverpool School of Tropical Medicine; Institut Pasteur, Paris; University of Birmingham; St George's University of London; Kenya Medical Research Institute; Centers for Disease Control and Prevention; Emory Global Health Institute; University of Liverpool; University of Malawi College of Medicine; Prins Leopold Instituut voor Tropische Geneeskunde; KU Leuven; National Institute for Biomedical Research; University Hospital of Kinshasa; University of Witwatersrand; Public Health England; St Augustine's Hospital; University of Abuja; Bingham University; Quadram Institute Bioscience; Universidad de la Republica Instituto de Higiene; Ministry of Health; Fiji Health Sector Support Program; National Institute of Cholera and Enteric Diseases India; ANLIS-Carlos G Malbran Institute; Nagasaki University; Oxford University Clinical Research Unit; Murdoch Children's Research Institute; Institute of Environmental Science and Research Limited (ESR); ESR - Kenepuru Science Centre; Samoa Ministry of Health; Organisation Mondiale de la Sante; Hasanuddin University; Tupua Tamasese Meaole Hospital; Mahidol University; Angkor Hospital for Children; University of Otago; Cardiff University; Barts and The London NHS Trust; University of Cambridge
    © 2016 Public Library of Science. All rights reserved. Background: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid.
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    Secondary Acute Myelogenous Leukemia in Patients with Retinoblastoma. Is Chemotherapy a Factor?
    (2007-07-01) Dan S. Gombos; John Hungerford; David H. Abramson; Judith Kingston; Guillermo Chantada; Ira J. Dunkel; Celia B.G. Antoneli; Mark Greenwald; Barret G. Haik; Carlos A. Leal; Aurora Medina-Sanson; Amy C. Schefler; Gavivann Veerakul; Regina Wieland; Norbert Bornfeld; Mathew W. Wilson; Christopher Bing On Yu; University of Texas MD Anderson Cancer Center; Barts and The London NHS Trust; Moorfields Eye Hospital NHS Foundation Trust; Memorial Sloan-Kettering Cancer Center; Hospital JP Garrhan; Hospital Sao Paulo; University of Chicago; University of Tennessee Health Science Center; Instituto Nacional de Pediatria; Hospital Infantil de Mexico Federico Gomez; University of Miami Leonard M. Miller School of Medicine; Mahidol University; Universitat Duisburg-Essen; Chinese University of Hong Kong
    Purpose: To describe a series of patients with secondary acute myelogenous leukemia (sAML) and retinoblastoma (RB). Design: Retrospective observational cases series. Participants: Ocular and pediatric oncologists at referral centers in Europe and the Americas and the RB databases at the National Institutes of Health and the Ophthalmic Oncology Service at Memorial Sloan-Kettering Cancer Center. Methods: Physician survey, retrospective database review, and literature search. Main Outcome Measures: History of RB and development of sAML, management of RB (surgery, radiotherapy, chemotherapy), age at diagnosis of RB and leukemia, French-American-British (FAB) subtype, and current status of patient (alive or dead). Results: Fifteen patients with sAML were identified; 13 occurred in childhood. Mean latent period from RB to AML diagnosis was 9.8 years (median, 42 months). Nine cases were of the M2 or M5 FAB subtypes. Twelve patients (79 %) had received chemotherapy with a topoisomerase II inhibitor, 8 (43%) had received chemotherapy with an epipodophyllotoxin. Ten children died of their leukemia. Conclusions: Acute myelogenous leukemia is a rare secondary malignancy among retinoblastoma patients, many of whom were treated with primary or adjuvant chemotherapy. Additional studies are needed to assess potential risk factors contributing to sAML development in this cohort. © 2007 American Academy of Ophthalmology.