407 results on '"Cummings, F."'
Search Results
152. Six-year results of the Eastern Cooperative Oncology Group trial of observation versus CMFP versus CMFPT in postmenopausal patients with node-positive breast cancer.
- Author
-
Taylor, S G, primary, Knuiman, M W, additional, Sleeper, L A, additional, Olson, J E, additional, Tormey, D C, additional, Gilchrist, K W, additional, Falkson, G, additional, Rosenthal, S N, additional, Carbone, P P, additional, and Cummings, F J, additional
- Published
- 1989
- Full Text
- View/download PDF
153. THE IMPACT OF ATHABASCA UNIVERSITY ON THE ATHABASCA AREA: INTERIM ASSESSMENT
- Author
-
Cummings, F. Harry, primary and Asselstine, Maralee, additional
- Published
- 1986
- Full Text
- View/download PDF
154. The particle in a box is not simple
- Author
-
Cummings, F. E., primary
- Published
- 1977
- Full Text
- View/download PDF
155. Exact solution for spontaneous emission in the presence ofNatoms
- Author
-
Cummings, F. W., primary and Dorri, Ali, additional
- Published
- 1983
- Full Text
- View/download PDF
156. Spontaneous Emission from an Excited Atom in the Presence ofNAtoms andMModes
- Author
-
Cummings, F. W., primary
- Published
- 1985
- Full Text
- View/download PDF
157. Discussion: “History and Performance of the Oil-Refinery Steam-Electric Generating Stations of the Pacific Gas and Electric Company” (Estcourt, V. F., 1950, Trans. ASME, 72, pp. 209–216)
- Author
-
Cummings, F. S., primary
- Published
- 1950
- Full Text
- View/download PDF
158. Installation and Acceptance of Postal Engineering Plant
- Author
-
Cummings, F. G., primary
- Published
- 1969
- Full Text
- View/download PDF
159. Discussion: “Power Development in the Southeast” (Adsit, Charles G., 1922, Trans. ASME, 44, pp. 341–355)
- Author
-
Thurlow, O. G., primary, Cummings, F. P., additional, Brown, C. S., additional, Orrok, George A., additional, Wilcox, W. F., additional, Wells, Warren M., additional, and Adsit, Charles G., additional
- Published
- 1922
- Full Text
- View/download PDF
160. Dynamics of a System ofNAtoms Interacting With a Radiation Field
- Author
-
Buley, E. R., primary and Cummings, F. W., additional
- Published
- 1964
- Full Text
- View/download PDF
161. Human IgG Cryoglobulin with Tubular Crystal Structure
- Author
-
BOGAARS, H. A., primary, KALDERON, A. E., additional, CUMMINGS, F. J., additional, KAPLAN, S., additional, MELNICOFF, I., additional, PARK, C., additional, DIAMOND, I., additional, and CALABRESI, P., additional
- Published
- 1973
- Full Text
- View/download PDF
162. Stimulated Emission of Radiation in a Single Mode
- Author
-
Cummings, F. W., primary
- Published
- 1965
- Full Text
- View/download PDF
163. The Birmingham New Parcel and Letter Sorting Office
- Author
-
Cummings, F. G., primary
- Published
- 1969
- Full Text
- View/download PDF
164. ON THE EFFECT OF AN ERROR IN A STANDARD D2O-MODERATED 252Cf ENERGY SPECTRUM.
- Author
-
Cummings, F. M.
- Subjects
NEUTRONS ,DEUTERIUM oxide ,RADIATION doses ,MEDICAL physics - Abstract
The article notes the error in the neutron fluence for neutrons with energies between 9 and 10 Million electron Volts (MeV) for the tabulated deuterium oxide (D
2 O)-moderated continuous flow (252 Cf) source in the International Organization for Standardization (ISO) 8529-1. It compared the moderated252 Cf neutron spectrum from ISO 8529-1 with the bare252 Cf spectrum in ISO 8529-1. It also computed the normalized dose conversion coefficient for each of the spectra.- Published
- 2009
- Full Text
- View/download PDF
165. AODTH-005 Transcriptomic profiling of intestinal macrophages isolated from patients reveals a profound gene expression reprogramming underlying ibd pathogenesis
- Author
-
Dharmasiri, S, Garrido-Martin, EM, Cummings, F, and Sanchez-Elsner, T
- Abstract
IntroductionMacrophages play a major role as effector cells of the innate immune system and are vital for intestinal tissue homeostasis. An altered function of intestinal macrophages may contribute to the development and propagation of intestinal inflammation in IBD. However, all data available come from mouse models, human whole tissue or in vitroderived macrophages from blood monocytes. We have isolated intestinal macrophages from patients and healthy subjects and analysed their transcriptome in order to study the intrinsic role that macrophages play in the pathogenesis of IBD.MethodFresh colonic mucosal tissue biopsies from 10 CD patients, 10 UC patients and 10 healthy controls were disaggregated to cell suspensions and sorted using fluorescence-activated cell sorting. RNA from intestinal macrophages, identified as CD163+CD14+CD3- population, was extracted and subjected to RNA sequencing. Differential Gene Expression analysis and pathway analysis were performed between the groups.ResultsThe transcriptomic analysis revealed that the gene expression profile of the intestinal macrophages from IBD is dramatically reprogrammed. Differential Gene Expression analysis revealed 1287 DEGs between macrophages from UC patients and healthy controls; 840 DEGs between macrophages from CD patients and healthy controls and 20 DEGs between macrophages from UC and CD patients (1.5 fold change and FDR<0.1).ConclusionThis is the first study to describe the transcriptome of intestinal macrophages from active lesions of patients with IBD by high throughput RNAseq. We show that the transcriptome of these macrophages is profoundly different from those taken from healthy subjects. These results suggest that macrophages play an important role in the propagation of inflammation and we have identified a number of molecules that should be investigated as potential therapeutic targets.Disclosure of InterestNone Declared[Figure]
- Published
- 2017
- Full Text
- View/download PDF
166. PTU-055 Interim data and experience in the ibd anaemia service evaluation project – a new role for the ibd registry
- Author
-
Silva, A Castro, Waddingham, W, Oliver, D, Knight, P, Johnson, M, Bloom, S, Magwenzi, S, Munro, C, and Cummings, F
- Abstract
IntroductionIron deficiency anaemia (IDA) is a common complication of Crohn’s disease (CD) and Ulcerative Colitis (UC), with estimated prevalence between 36%–76%. Both IDA and its treatment can be associated with significant disease morbidity, particularly fatigue. This 12 month pilot investigation, preceding a wider UK audit, aims to utilise the IBD Registry Web Tool to capture the prevalence of IDA in an outpatient setting and the consistency and quality of treatment patients receive, which are currently uncertain.MethodIn a Joint Working project between the IBD Registry and Pharmacosmos, patients were recruited at 5 hospitals: UCLH, Southampton, UHSM, James Cook, and Luton and Dunstable. At each site, 20 consecutive patients were recruited until 10 patients with CD and 10 with UC were enrolled, giving a total of 100 patients for the study. Patients gave permission for their data including demographics, disease activity scores, IBD Control Questionnaire, and blood parameters relating to IDA to be used by the Anaemia Service Evaluation and IBD Registry.ResultsWe report baseline data for patients at enrolment. Average age was 44 years 11mos (19–90 years). Mean HBI score was 3.7 based on 57 recorded scores and UCDAI was 2.4 from 13 patients. Using the Physician’s Global Assessment, 3.7% had severe, 13.4% moderate, 26.8% mildly active and 56.1% quiescent disease. 18 patients were anaemic; 9 men and 9 women, with mean Hb114.4±13.7 g/L and 110.9±4.2 g/L respectively. 9 additional patients were iron deficient without anaemia. In anaemic patients, mean ferritin and CRP were 100.3 µg/L and 12.1 mg/L respectively. Ferritin and CRP were 69.9 µg/L and 7.7 mg/L in non-anaemic patients. Mean patient-reported IBD control-8 scores (range 0–16) were 11.47 (anaemic) and 11.45 (non-anaemic). 52 patients reported fatigue while 26 missed activities due to their disease.ConclusionIn this pilot study, once patients were consented and entered on the IBD Registry Web Tool, adding blood results and disease scores was straightforward. This could easily be done in an outpatient clinic setting once the clinician is familiar with the process. This initial data set confirms the feasibility of effectively monitoring anaemia with the IBD Registry to enhance detection of under-recognised symptoms such as fatigue and help improve patient care. Our initial experience suggests that the IBD Registry serves as a reliable and meaningful way of capturing quality improvement data regarding IDA and its treatment in IBD.Disclosure of InterestNone Declared
- Published
- 2017
- Full Text
- View/download PDF
167. PTH-096 Improved outcomes of emergency admission for ulcerative colitis (uc) in england over the last decade: a ten year analysis of routine nhs data
- Author
-
Shawihdi, M, Dodd, S, Grainger, R, Bloom, S, Cummings, F, Driscoll, R, Pearson, M, Williamson, P, and Bodger, K
- Abstract
IntroductionHypothesis:Over the last decade, therapy advances and a national audit programme should have improved outcomes for UC patients admitted as emergencies (Em).MethodTo support IBD Registry analytics, we have developed metrics from routine NHS data to allow reporting of trends in national-level indicators of IBD care.Design:Retrospective analysis of 10 years of HES data for England. Target population:54,533 Em. admissions with UC as primary diagnosis (April ‘05 to March ‘13; n=37 170 patients). Binary Outcome Measures: Surgery (colectomy) during index admission (Sx-Index) or within 1 year (Sx-1-Year); Em. readmission within 30 days of discharge (Readmit-30d); Inpatient death during index admission (Death-Index). Case-mix Variables: Age, Gender, Co-morbidities (0, 1 or 2+, Charlson), Deprivation Status (IMD Quintiles), Any Cancer, Em. bed bays (all-cause) in preceding year (EmBedDaysLastYr). Predictor Variable:Year of Admission (Yr-Adm). Analyses:Uni- and multivariable logistic regression (stepwise), reporting adjusted odds ratios (OR) for retained variables. Adjusted for repeat admissions in same patient (clustered standard errors).ResultsMultivariable Models: OR for Sx-Indexwas reducedwith increased age (0.98 per yr), 2+ co-morbidities (0.81 vs. none), females (0.74 vs. male) and for >28 EmBedDaysLastYr. OR for Death-Indexwas increasedwith increased age (1.10 per yr), co-morbidities (1.87 for one, 3.2 for two or more, vs none) and colectomy during admission (6.99 vs. no surgery) but reducedfor >28 EmBedDaysLastYr (0.88 vs. none). Models for Sx-1-Yearshowed a similar pattern with respect to reduced OR for age, co-morbidity and females. For Readmit-30d, the most significant factor associated with reducedOR was colectomy during admission (0.43), whereas >28 EmBedDaysLastYr was associated with increasedOR (2.0 vs. none). Deprivation status was not independently associated with any outcome. After adjusting for these co-variates, Yr-Adm was associated with a significant reduction in OR for both Sx-Index and Death-Index, with OR of 0.98(0.976–0.998) and 0.91(0.88, 0.94) per yr relative to base year. Models for all-cause admissions did not show these trends, suggesting condition-specific findings.ConclusionRisk of colectomy and inpatient death for UC patients admitted as emergencies to English hospitals has reduced over the last 10 years. Many factors may explain these trends, but cycles of UK-wide IBD audit are likely contributors. We found no signal for social inequality, but a reduced odds of surgery for females requires further study.Funding: Crohn’s and Colitis UKDisclosure of InterestM. Shawihdi: None Declared, S Dodd: None Declared, R Grainger: None Declared, S Bloom: None Declared, F Cummings: None Declared, R Driscoll: None Declared, M Pearson: None Declared, P Williamson: None Declared, K Bodger Conflict with: AbbVie, Conflict with: Boston Scientific | Takeda
- Published
- 2017
- Full Text
- View/download PDF
168. PTH-090 Monitoring unplanned care and surgical events for crohn’s disease patients treated with biologics in england: linkage of routine administrative data and uk ibd registry
- Author
-
Shawihdi, M, Driscoll, R, Bloom, S, Cummings, F, Grainger, S, Johnson, M, Pearson, M, and Bodger, K
- Abstract
IntroductionThe UK IBD Registry (UK-IBD-R) is developing analyses of Hospital Episode Statistics (HES) with linkage to locally-recorded registry data to generate aggregated reports and indicators to support IBD services. We have created methods to categorise relevant hospital events and track outcomes in HES. For this project, we produced metrics of unplanned care and surgical events before and after initiation of biologics, generating a national scale analysis from HES alone and a proof-of-concept study with linkage to UK-IBD-R.MethodDatasets:HES for England (04/05 to 13/14); UK-IBD-R dataset (to June 2016). Patientcohorts: (1) HES cohortidentified using HES only. We flagged all admissions (incl. daycases) with a diagnosis of CD and procedure code X921 (biologic infusion; assumed to be infliximab), locating 1 st infusion for each case; (2) Registry cohortwas based on anonymized linkage (undertaken by NHS Digital), identifying cases with a registry-recorded diagnosis of CD, a medication entry for anti-TNF drug (infliximab, inflectra or adalimumab) and a valid start date. Hospital events in HES:All-cause episodes were extracted for 1 year before (Yr-Pre) and after (Yr-Post) start of treatment, categorising each inpatient and daycase event based on admission method, diagnoses (IBD-specific, IBD-related and Other) and procedures.[Figure]ResultsHES cohort:n=15 399 (Age: 35 [16]; 47% male); Registry cohort:n=217 (Age: 26 [13.5]; 56% male). Unplanned care activity for Yr-Pre versus Yr-Post are shown in Abstract PTH090 Figure 1, confirming substantial reductions in all-cause and CD-specific emergency care following initiation of biologics in routine UK practice (p<0.05). Of HES cohort, 10 877 (71%) continued infusion visits beyond induction phase (’Maintenance’), and 4522 (29%) did not (’Stopped’). Surgical resections at 1 year:Total, 944 (6.2%); Maintenance versus Stopped: 395 (3.6%) v. 549 (12%), p<0.05. Emergency admissions with ‘infections’ at 1 year: Total, 222 (1.4%); Maintenance versus Stopped: 146 (1.3%) v. 76 (1.7%), p=0.11.ConclusionThese national scale data provide new insights into activity, costs and outcomes associated with routine use of biologics for CD in England. Linkage between UK-IBD-R and HES provides a potentially powerful tool for monitoring of activity, process and outcome of IBD care. The use of existing datasets reduces the burden of local point-of-care data collection, allowing focus on collecting items to enhance accuracy and clinical depth of analyses. [Funding: Crohn’s and Colitis UK]Disclosure of InterestNone Declared
- Published
- 2017
- Full Text
- View/download PDF
169. PTH-072 An exploratory study of the impact of primary care faecal calprotectin testing on referrals to secondary care
- Author
-
Taylor, N, Everitt, H, Latter, S, Burrill, K, Efrem, E, and Cummings, F
- Abstract
IntroductionNICE recommend faecal calprotectin (FC) testing to help differentiate between irritable bowel syndrome and other pathologies including inflammatory bowel disease (IBD) in adults for whom specialist assessment is being considered. We aimed to explore the impact of introducing GP FC testing on referrals to secondary care.MethodGPs within Southampton City and West Hampshire CCGs were invited to request FC in adults under 45 with symptoms that could initiate referral. Before requesting electronically, GPs answered questions on patient history and if they planned to refer the patient. GP/hospital data was collected electronically from April 2015-June 2016 and reviewed according to FC (<50: negative, 50–99: indeterminate, ≥100: positive) as a service evaluation.Results59/64 (92%) of GP surgeries used FC testing. 410/435 samples received were processed: 66 (16%) positive, 33 (8%) indeterminate, 311 (76%) negative. 85/410 (21%) patients were referred to secondary care (60% positive/indeterminate FC). Mean monthly gastroenterology (including non-IBD) referral rates were unchanged from 2014/15 to 2015/16 (187 vs. 186/mth). 16/410 were diagnosed with IBD (19% of FC referrals, all positive/indeterminate FC). Of 66 patients with positive FC, only 43 (65%) were referred, with no referral/appointment on record for the remaining 23.When asked ‘would you refer even if FC was negative?’ in 55/410 cases GPs responded ‘yes’, but only referred 22 (40%). Of 176/410 cases where the response was ‘no’, 13 (7%) were referred. When asked ‘would you refer if FC was not available?’ in 205/410 cases GPs responded ‘yes’ but only referred 52 (25%). Of 34/410 cases where the response was ‘no’, 4 (12%) were referred. GPs were twice as likely to report planning to refer patients who ultimately had a positive FC than those with a negative FC (24% vs. 11%), suggesting these patients may have symptoms of greater concern.56/85 (66%) of referred patients (14 with negative FC) underwent lower GI endoscopy (30/56 (53%) normal, 16/56 (29%) IBD, 4/56 (7%) microscopic colitis, 1/56 (2%) cancer, 5/56 (9%) other). Mean times from referral to outpatient clinic and endoscopy: 69 and 93 days. Despite being at higher risk of IBD, the mean time from referral to clinic for patients with positive FC was only slightly less than for negative FC (64 vs. 78 days).ConclusionFC testing was requested by most GP practices but in low numbers and a significant number of patients with positive FC were not referred. FC did appear to influence GP decision-making regarding referral. Local pathways will be developed to introduce a Positive FC clinic to streamline referrals and aim to improve time to IBD diagnosis.Disclosure of InterestNone Declared
- Published
- 2017
- Full Text
- View/download PDF
170. Continuous chaotic dynamics in two dimensions
- Author
-
Dixon, D. D., Cummings, F. W., and Kaus, P. E.
- Published
- 1993
- Full Text
- View/download PDF
171. Aspects of growth and form
- Author
-
Cummings, F. W.
- Published
- 1994
- Full Text
- View/download PDF
172. Attention.
- Author
-
Cummings, F. H.
- Published
- 1903
173. Smith-Weathington.
- Author
-
CUMMINGS, F. H.
- Published
- 1901
174. A. V. E. Convention.
- Author
-
Cummings, F. H.
- Published
- 1901
175. UNTITLED.
- Author
-
Cummings, F.
- Published
- 1907
176. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study
- Author
-
Silvio Danese, Jean-Frederic Colombel, Milan Lukas, Javier P Gisbert, Geert D'Haens, Bu'hussain Hayee, Remo Panaccione, Hyun-Soo Kim, Walter Reinisch, Helen Tyrrell, Young S Oh, Swati Tole, Akiko Chai, Kirsten Chamberlain-James, Meina Tao Tang, Stefan Schreiber, Nazimuddin Aboo, Tariq Ahmad, Xavier Aldeguer Mante, Matthieu Allez, Sven Almer, Romain Altwegg, Montserrat Andreu Garcia, Ramesh Arasaradnam, Sandro Ardizzone, Alessandro Armuzzi, Ian Arnott, Guy Aumais, Irit Avni-Biron, Peter Barrow, Ian Beales, Fernando Bermejo San Jose, Abraham Bezuidenhout, Livia Biancone, Michael Blaeker, Stuart Bloom, Bernd Bokemeyer, Fabrizio Bossa, Peter Bossuyt, Guillaume Bouguen, Yoram Bouhnik, Gerd Bouma, Raymond Bourdages, Arnaud Bourreille, Christian Boustiere, Tomas Brabec, Stephan Brand, Carsten Buening, Anthony Buisson, Guillaume Cadiot, Xavier Calvet Calvo, Franck Carbonnel, Daniel Carpio, Jae Hee Cheon, Naoki Chiba, Camelia Chioncel, Nicoleta-Claudia Cimpoeru, Martin Clodi, Gino Roberto Corazza, Rocco Cosintino, Jose Cotter, Thomas Creed, Fraser Cummings, Gian Luigi de' Angelis, Marc De Maeyer, Milind Desai, Etienne Desilets, Pierre Desreumaux, Olivier Dewit, Johanna Dinter, Ecaterina Daniela Dobru, Tomas Douda, Dan Lucian Dumitrascu, Matthias Ebert, Ana Echarri Piudo, Magdy Elkhashab, Chang Soo Eun, Brian Feagan, Roland Fejes, Catarina Fidalgo, Sigal Fishman, Bernard Flourié, Sharyle Fowler, Walter Fries, Csaba Fulop, Mathurin Fumery, Gyula G Kiss, Sonja Gassner, Daniel Gaya, Bastianello Germanà, Liliana Simona Gheorghe, Cyrielle Gilletta de Saint Joseph, Paolo Gionchetti, Adrian-Eugen Goldis, Raquel Gonçalves, Jean-Charles Grimaud, Tibor Gyökeres, Herve Hagege, Andrei Haidar, Heinz Hartmann, Peter Hasselblatt, Buhussain Hayee, Xavier Hebuterne, Per Hellström, Pieter Hindryckx, Helena Hlavova, Frank Hoentjen, Stefanie Howaldt, Ludek Hrdlicka, Kyu Chan Huh, Maria Isabel Iborra Colomino, Florentina Ionita-Radu, Peter Irving, Jørgen Jahnsen, ByungIk Jang, Jeroen Jansen, Seong Woo Jeon, Rodrigo Jover Martinez, Pascal Juillerat, Per Karlén, Arthur Kaser, Radan Keil, Deepak Kejariwal, Dan Keret, Reena Khanna, Dongwoo Kim, Duk Hwan Kim, Hyo-Jong Kim, Joo Sung Kim, Kueongok Kim, Kyung-Jo Kim, Sung Kook Kim, Young-Ho Kim, Jochen Klaus, Anna Kohn, Vladimir Kojecky, Ja Seol Koo, Robert Kozak, Milan Kremer, Tunde Kristof, Frederik Kruger, David Laharie, Adi Lahat-zok, Evgeny Landa, Jonghun Lee, Kang-Moon Lee, Kook Lae Lee, YooJin Lee, Frank Lenze, Wee Chian Lim, Jimmy Limdi, James Lindsay, Pilar Lopez Serrano, Edouard Louis, Stefan Lueth, Giovanni Maconi, Fazia Mana, Steven Mann, John Mansfield, Santino Marchi, Marco Marino, John Marshall, Maria Dolores Martin Arranz, Radu-Bogdan Mateescu, John McLaughlin, Simon McLaughlin, Ehud Melzer, Jessica Mertens, Paul Mitrut, Tamas Molnar, Vinciane Muls, Pushpakaran Munuswamy, Charles Murray, Timna Naftali, Visvakuren Naidoo, Yusuf Nanabhay, Lucian Negreanu, Augustin Nguyen, Thomas Ochsenkuehn, Ambrogio Orlando, Julian Panes Diaz, Maya Paritsky, Dong Il Park, Jihye Park, Luca Pastorelli, Markus Peck-Radosavljevic, Farhad Peerani, Javier Perez Gisbert, Laurent Peyrin-Biroulet, Laurence Picon, Marieke Pierik, Terry Ponich, Francisco Portela, Maartens Jeroen Prins, Istvan Racz, Khan Fareed Rahman, Jean-Marie Reimund, Max Reinshagen, Xavier Roblin, Rodolfo Rocca, Francesca Rogai, Gerhard Rogler, Agnes Salamon, Ennaliza Salazar, Zoltan Sallo, Sunil Samuel, Miquel de los Santos Sans Cuffi, Edoardo Vincenzo Savarino, Vincenzo Savarino, Guillaume Savoye, Andrada Seicean, Christian Selinger, David Martins Serra, Hang Hock Shim, SungJae Shin, Britta Siegmund, Jesse Siffledeen, Wayne Simmonds, Jan Smid, Jose Sollano, Geun Am Song, Alexander Speight, Ioan Sporea, Dirk Staessen, George Stancu, Alan Steel, David Stepek, Victor Stoica, Andreas Sturm, Gyorgy Szekely, Teck Kiang Tan, Carlos Taxonera Samso, John Thomson, Michal Tichy, Gabor Tamas Toth, Zsolt Tulassay, Marcello Vangeli, Marta Varga, Ana Vieira, Stephanie Viennot, Erica Villa, Petr Vitek, Harald Vogelsang, Petr Vyhnalek, Peter Wahab, Jens Walldorf, Byong Duk Ye, Christopher Ziady, Danese S., Colombel J.-F., Lukas M., Gisbert J.P., D'Haens G., Hayee B., Panaccione R., Kim H.-S., Reinisch W., Tyrrell H., Oh Y.S., Tole S., Chai A., Chamberlain-James K., Tang M.T., Schreiber S., Aboo N., Ahmad T., Aldeguer Mante X., Allez M., Almer S., Altwegg R., Andreu Garcia M., Arasaradnam R., Ardizzone S., Armuzzi A., Arnott I., Aumais G., Avni-Biron I., Barrow P., Beales I., Bermejo San Jose F., Bezuidenhout A., Biancone L., Blaeker M., Bloom S., Bokemeyer B., Bossa F., Bossuyt P., Bouguen G., Bouhnik Y., Bouma G., Bourdages R., Bourreille A., Boustiere C., Brabec T., Brand S., Buening C., Buisson A., Cadiot G., Calvet Calvo X., Carbonnel F., Carpio D., Cheon J.H., Chiba N., Chioncel C., Cimpoeru N.-C., Clodi M., Corazza G.R., Cosintino R., Cotter J., Creed T., Cummings F., de' Angelis G.L., De Maeyer M., Desai M., Desilets E., Desreumaux P., Dewit O., Dinter J., Dobru E.D., Douda T., Dumitrascu D.L., Ebert M., Echarri Piudo A., Elkhashab M., Eun C.S., Feagan B., Fejes R., Fidalgo C., Fishman S., Flourie B., Fowler S., Fries W., Fulop C., Fumery M., G Kiss G., Gassner S., Gaya D., Germana B., Gheorghe L.S., Gilletta de Saint Joseph C., Gionchetti P., Goldis A.-E., Goncalves R., Grimaud J.-C., Gyokeres T., Hagege H., Haidar A., Hartmann H., Hasselblatt P., Hebuterne X., Hellstrom P., Hindryckx P., Hlavova H., Hoentjen F., Howaldt S., Hrdlicka L., Huh K.C., Iborra Colomino M.I., Ionita-Radu F., Irving P., Jahnsen J., Jang B., Jansen J., Jeon S.W., Jover Martinez R., Juillerat P., Karlen P., Kaser A., Keil R., Kejariwal D., Keret D., Khanna R., Kim D., Kim D.H., Kim H.-J., Kim J.S., Kim K., Kim K.-J., Kim S.K., Kim Y.-H., Klaus J., Kohn A., Kojecky V., Koo J.S., Kozak R., Kremer M., Kristof T., Kruger F., Laharie D., Lahat-zok A., Landa E., Lee J., Lee K.-M., Lee K.L., Lee Y., Lenze F., Lim W.C., Limdi J., Lindsay J., Lopez Serrano P., Louis E., Lueth S., Maconi G., Mana F., Mann S., Mansfield J., Marchi S., Marino M., Marshall J., Martin Arranz M.D., Mateescu R.-B., McLaughlin J., McLaughlin S., Melzer E., Mertens J., Mitrut P., Molnar T., Muls V., Munuswamy P., Murray C., Naftali T., Naidoo V., Nanabhay Y., Negreanu L., Nguyen A., Ochsenkuehn T., Orlando A., Panes Diaz J., Paritsky M., Park D.I., Park J., Pastorelli L., Peck-Radosavljevic M., Peerani F., Perez Gisbert J., Peyrin-Biroulet L., Picon L., Pierik M., Ponich T., Portela F., Prins M.J., Racz I., Rahman K.F., Reimund J.-M., Reinshagen M., Roblin X., Rocca R., Rogai F., Rogler G., Salamon A., Salazar E., Sallo Z., Samuel S., Sans Cuffi M.D.L.S., Savarino E.V., Savarino V., Savoye G., Seicean A., Selinger C., Serra D.M., Shim H.H., Shin S., Siegmund B., Siffledeen J., Simmonds W., Smid J., Sollano J., Song G.A., Speight A., Sporea I., Staessen D., Stancu G., Steel A., Stepek D., Stoica V., Sturm A., Szekely G., Tan T.K., Taxonera Samso C., Thomson J., Tichy M., Toth G.T., Tulassay Z., Vangeli M., Varga M., Vieira A., Viennot S., Villa E., Vitek P., Vogelsang H., Vyhnalek P., Wahab P., Walldorf J., Ye B.D., and Ziady C.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Population ,Antibodies, Monoclonal, Humanized ,Injections, Subcutaneou ,Placebo ,Severity of Illness Index ,Gastroenterology ,Young Adult ,Double-Blind Method ,Internal medicine ,Gastrointestinal Agent ,Clinical endpoint ,medicine ,education ,Adverse effect ,Aged ,Aged, 80 and over ,education.field_of_study ,Hepatology ,business.industry ,Middle Aged ,medicine.disease ,Ulcerative colitis ,Infliximab ,Treatment Outcome ,Etrolizumab ,Concomitant ,Colitis, Ulcerative ,Female ,business ,Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] ,Human ,medicine.drug - Abstract
Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.
- Published
- 2022
177. Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial
- Author
-
Laurent Peyrin-Biroulet, Ailsa Hart, Peter Bossuyt, Millie Long, Matthieu Allez, Pascal Juillerat, Alessandro Armuzzi, Edward V Loftus, Elham Ostad-Saffari, Astrid Scalori, Young S Oh, Swati Tole, Akiko Chai, Jennifer Pulley, Stuart Lacey, William J Sandborn, Humberto Aguilar, Tariq Ahmad, Evangelos Akriviadis, Xavier Aldeguer Mante, Istvan Altorjay, Ashwin Ananthakrishnan, Vibeke Andersen, Montserrat Andreu Garcia, Guy Aumais, Irit Avni-Biron, Jeffrey Axler, Kamran Ayub, Filip Baert, Mauro Bafutto, George Bamias, Isaac Bassan, Curtis Baum, Laurent Beaugerie, Brian Behm, Pradeep Bekal, Michael Bennett, Fernando Bermejo San Jose, Charles Bernstein, Dominik Bettenworth, Sudhir Bhaskar, Livia Biancone, Bahri Bilir, Michael Blaeker, Stuart Bloom, Verle Bohman, Francisco Javier Bosques Padilla, Yoram Bouhnik, Gerd Bouma, Raymond Bourdages, Stephan Brand, Brian Bressler, Markus Brückner, Carsten Buening, Franck Carbonnel, Thomas Caves, Jonathon Chapman, Jae Hee Cheon, Naoki Chiba, Camelia Chioncel, Dimitrios Christodoulou, Martin Clodi, Albert Cohen, Gino Roberto Corazza, Richard Corlin, Rocco Cosintino, Fraser Cummings, Robin Dalal, Silvio Danese, Marc De Maeyer, Carlos Fernando De Magalhães Francesconi, Aminda De Silva, Henry Debinski, Pierre Desreumaux, Olivier Dewit, Geert D'Haens, Sandra Di Felice Boratto, John Nik Ding, Tyler Dixon, Gerald Dryden, George Aaron Du Vall, Matthias Ebert, Ana Echarri Piudo, Robert Ehehalt, Magdy Elkhashab, Craig Ennis, Jason Etzel, Jan Fallingborg, Brian Feagan, Roland Fejes, Daniel Ferraz de Campos Mazo, Valéria Ferreira de Almeida Borges, Andreas Fischer, Alan Fixelle, Mark Fleisher, Sharyle Fowler, Bradley Freilich, Keith Friedenberg, Walter Fries, Csaba Fulop, Mathurin Fumery, Sergio Fuster, Gyula G Kiss, Santiago Garcia Lopez, Sonja Gassner, Kanwar Gill, Cyrielle Gilletta de Saint Joseph, Philip Ginsburg, Paolo Gionchetti, Eran Goldin, Adrian-Eugen Goldis, Hector Alejandro Gomez Jaramillo, Maciej Gonciarz, Glenn Gordon, Daniel Green, Jean-Charles Grimaud, Rogelio Guajardo Rodriguez, Zoltan Gurzo, Alexandra Gutierrez, Tibor Gyökeres, Ki Baik Hahm, Stephen Hanauer, John Hanson, William Harlan III, Peter Hasselblatt, Buhussain Hayee, Xavier Hebuterne, Peter Hendy, Melvin Heyman, Peter Higgins, Raouf Hilal, Pieter Hindryckx, Frank Hoentjen, Peter Hoffmann, Frank Holtkamp-Endemann, Gerald Holtmann, Gyula Horvat, Stefanie Howaldt, Samuel Huber, Ikechukwu Ibegbu, Maria Isabel Iborra Colomino, Peter Irving, Kim Isaacs, Kiran Jagarlamudi, Rajesh Jain, Sender Jankiel Miszputen, Jeroen Jansen, Jennifer Jones, John Karagiannis, Nicholas Karyotakis, Arthur Kaser, Lior Katz, Seymour Katz, Leo Katz, Nirmal Kaur, Edita Kazenaite, Reena Khanna, Sunil Khurana, Joo Sung Kim, Young-Ho Kim, Sung Kook Kim, Dongwoo Kim, Jochen Klaus, Dariusz Kleczkowski, Pavel Kohout, Bartosz Korczowski, Georgios Kouklakis, Ioannis Koutroubakis, Richard Krause, Tunde Kristof, Ian Kronborg, Annette Krummenerl, Limas Kupcinskas, Jorge Laborda Molteni, David Laharie, Adi Lahat-zok, Jonghun Lee, Kang-Moon Lee, Rupert Leong, Henry Levine, Jimmy Limdi, James Lindsay, Nilesh Lodhia, Edward Loftus, Randy Longman, Pilar Lopez Serrano, Edouard Louis, Maria Helena Louzada Pereira, John Lowe, Stefan Lueth, Milan Lukas, Giovanni Maconi, Finlay Macrae, Laszlo Madi-Szabo, Uma Mahadevan-Velayos, Everson Fernando Malluta, Fazia Mana, Peter Mannon, Gerasimos Mantzaris, Ignacio Marin Jimenez, Maria Dolores Martin Arranz, Radu-Bogdan Mateescu, Felipe Mazzoleni, Agnieszka Meder, Ehud Melzer, Jessica Mertens, Konstantinos Mimidis, Brent Mitchell, Tamas Molnar, Gregory Moore, Luis Alonso Morales Garza, Reme Mountifield, Vinciane Muls, Charles Murray, Bela Nagy, Markus Neurath, Augustin Nguyen, Remo Panaccione, William Pandak, Julian Panes Diaz, Jihye Park, Luca Pastorelli, Bhaktasharan Patel, Markus Peck-Radosavljevic, Gyula Pecsi, Farhad Peerani, Javier Perez Gisbert, Martin Pesta, Robert Petryka, Raymond Phillips, Marieke Pierik, Vijayalakshmi Pratha, Vlastimil Prochazka, Istvan Racz, Graham Radford-Smith, Daniel Ramos Castañeda, Odery Ramos Júnior, Jaroslaw Regula, Jean-Marie Reimund, Bryan Robbins, Xavier Roblin, Francesca Rogai, Gerhard Rogler, Jerzy Rozciecha, David Rubin, Azalia Yuriria Ruiz Flores, Maciej Rupinski, Grazyna Rydzewska, Sumona Saha, Simone Saibeni, Agnes Salamon, Zoltan Sallo, Bruce Salzberg, Douglas Samuel, Sunil Samuel, William Sandborn, Edoardo Vincenzo Savarino, Anja Schirbel, Robert Schnabel, Stefan Schreiber, John Scott, Shahriar Sedghi, Frank Seibold, Jakob Seidelin, Ursula Seidler, Ahmad Shaban, Ira Shafran, Aasim Sheikh, Alex Sherman, Haim Shirin, Patryk Smolinski, Geun Am Song, Konstantinos Soufleris, Alexander Speight, Dirk Staessen, Andreas Stallmach, Michael Staun, Daniel Stein, Hillary Steinhart, Jonathas Stifft, David Stokesberry, Andreas Sturm, Keith Sultan, Gyorgy Szekely, Kuldeep Tagore, Hugo Tanno, Lena Thin, Syed Thiwan, Carlton Thomas, Michal Tichy, Gabor Tamas Toth, Zsolt Tulassay, Jan Ulbrych, John Valentine, Marta Varga, Eduardo Vasconcellos, Byron Vaughn, Brenda Velasco, Francisco Velazquez, Severine Vermeire, Erica Villa, Aron Vincze, Harald Vogelsang, Miroslava Volfova, Lucine Vuitton, Petr Vyhnalek, Peter Wahab, Jens Walldorf, Mattitiahu Waterman, John Weber, L. Michael Weiss, Anna Wiechowska-Kozlowska, Elise Wiesner, Thomas Witthoeft, Robert Wohlman, Barbara Wozniak-Stolarska, Bruce Yacyshyn, Byong-Duk Ye, Ziad Younes, Lígia Yukie Sassaki, Cyrla Zaltman, Stefan Zeuzem, Neurosurgery, ANS - Neurovascular Disorders, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Peyrin-Biroulet L., Hart A., Bossuyt P., Long M., Allez M., Juillerat P., Armuzzi A., Loftus E.V., Ostad-Saffari E., Scalori A., Oh Y.S., Tole S., Chai A., Pulley J., Lacey S., Sandborn W.J., Aguilar H., Ahmad T., Akriviadis E., Aldeguer Mante X., Altorjay I., Ananthakrishnan A., Andersen V., Andreu Garcia M., Aumais G., Avni-Biron I., Axler J., Ayub K., Baert F., Bafutto M., Bamias G., Bassan I., Baum C., Beaugerie L., Behm B., Bekal P., Bennett M., Bermejo San Jose F., Bernstein C., Bettenworth D., Bhaskar S., Biancone L., Bilir B., Blaeker M., Bloom S., Bohman V., Bosques Padilla F.J., Bouhnik Y., Bouma G., Bourdages R., Brand S., Bressler B., Bruckner M., Buening C., Carbonnel F., Caves T., Chapman J., Cheon J.H., Chiba N., Chioncel C., Christodoulou D., Clodi M., Cohen A., Corazza G.R., Corlin R., Cosintino R., Cummings F., Dalal R., Danese S., De Maeyer M., De Magalhaes Francesconi C.F., De Silva A., Debinski H., Desreumaux P., Dewit O., D'Haens G., Di Felice Boratto S., Ding J.N., Dixon T., Dryden G., Du Vall G.A., Ebert M., Echarri Piudo A., Ehehalt R., Elkhashab M., Ennis C., Etzel J., Fallingborg J., Feagan B., Fejes R., Ferraz de Campos Mazo D., Ferreira de Almeida Borges V., Fischer A., Fixelle A., Fleisher M., Fowler S., Freilich B., Friedenberg K., Fries W., Fulop C., Fumery M., Fuster S., G Kiss G., Garcia Lopez S., Gassner S., Gill K., Gilletta de Saint Joseph C., Ginsburg P., Gionchetti P., Goldin E., Goldis A.-E., Gomez Jaramillo H.A., Gonciarz M., Gordon G., Green D., Grimaud J.-C., Guajardo Rodriguez R., Gurzo Z., Gutierrez A., Gyokeres T., Hahm K.B., Hanauer S., Hanson J., Harlan III W., Hasselblatt P., Hayee B., Hebuterne X., Hendy P., Heyman M., Higgins P., Hilal R., Hindryckx P., Hoentjen F., Hoffmann P., Holtkamp-Endemann F., Holtmann G., Horvat G., Howaldt S., Huber S., Ibegbu I., Iborra Colomino M.I., Irving P., Isaacs K., Jagarlamudi K., Jain R., Jankiel Miszputen S., Jansen J., Jones J., Karagiannis J., Karyotakis N., Kaser A., Katz L., Katz S., Kaur N., Kazenaite E., Khanna R., Khurana S., Kim J.S., Kim Y.-H., Kim S.K., Kim D., Klaus J., Kleczkowski D., Kohout P., Korczowski B., Kouklakis G., Koutroubakis I., Krause R., Kristof T., Kronborg I., Krummenerl A., Kupcinskas L., Laborda Molteni J., Laharie D., Lahat-zok A., Lee J., Lee K.-M., Leong R., Levine H., Limdi J., Lindsay J., Lodhia N., Loftus E., Longman R., Lopez Serrano P., Louis E., Louzada Pereira M.H., Lowe J., Lueth S., Lukas M., Maconi G., Macrae F., Madi-Szabo L., Mahadevan-Velayos U., Malluta E.F., Mana F., Mannon P., Mantzaris G., Marin Jimenez I., Martin Arranz M.D., Mateescu R.-B., Mazzoleni F., Meder A., Melzer E., Mertens J., Mimidis K., Mitchell B., Molnar T., Moore G., Morales Garza L.A., Mountifield R., Muls V., Murray C., Nagy B., Neurath M., Nguyen A., Panaccione R., Pandak W., Panes Diaz J., Park J., Pastorelli L., Patel B., Peck-Radosavljevic M., Pecsi G., Peerani F., Perez Gisbert J., Pesta M., Petryka R., Phillips R., Pierik M., Pratha V., Prochazka V., Racz I., Radford-Smith G., Ramos Castaneda D., Ramos Junior O., Regula J., Reimund J.-M., Robbins B., Roblin X., Rogai F., Rogler G., Rozciecha J., Rubin D., Ruiz Flores A.Y., Rupinski M., Rydzewska G., Saha S., Saibeni S., Salamon A., Sallo Z., Salzberg B., Samuel D., Samuel S., Sandborn W., Savarino E.V., Schirbel A., Schnabel R., Schreiber S., Scott J., Sedghi S., Seibold F., Seidelin J., Seidler U., Shaban A., Shafran I., Sheikh A., Sherman A., Shirin H., Smolinski P., Song G.A., Soufleris K., Speight A., Staessen D., Stallmach A., Staun M., Stein D., Steinhart H., Stifft J., Stokesberry D., Sturm A., Sultan K., Szekely G., Tagore K., Tanno H., Thin L., Thiwan S., Thomas C., Tichy M., Toth G.T., Tulassay Z., Ulbrych J., Valentine J., Varga M., Vasconcellos E., Vaughn B., Velasco B., Velazquez F., Vermeire S., Villa E., Vincze A., Vogelsang H., Volfova M., Vuitton L., Vyhnalek P., Wahab P., Walldorf J., Waterman M., Weber J., Weiss L.M., Wiechowska-Kozlowska A., Wiesner E., Witthoeft T., Wohlman R., Wozniak-Stolarska B., Yacyshyn B., Ye B.-D., Younes Z., Yukie Sassaki L., Zaltman C., and Zeuzem S.
- Subjects
Adult ,Male ,Ulcerative Colitis Flare ,medicine.medical_specialty ,Asia ,Adolescent ,Oceania ,Population ,Antibodies, Monoclonal, Humanized ,Injections, Subcutaneou ,Placebo ,Severity of Illness Index ,law.invention ,Middle East ,Young Adult ,Maintenance therapy ,Randomized controlled trial ,law ,Internal medicine ,Gastrointestinal Agent ,medicine ,Adverse effect ,education ,Aged ,Aged, 80 and over ,Tumor Necrosis Factor Inhibitor ,education.field_of_study ,Hepatology ,business.industry ,Remission Induction ,Gastroenterology ,Middle Aged ,South America ,medicine.disease ,Ulcerative colitis ,Europe ,Treatment Outcome ,Etrolizumab ,North America ,Colitis, Ulcerative ,Female ,business ,Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] ,Human - Abstract
Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.
- Published
- 2022
178. Anti-TNF biosimilars in Crohn’s Disease: a patient-centric interdisciplinary approach
- Author
-
Laurent Peyrin-Biroulet, Taegyun Kang, Fraser Cummings, Kay Greveson, Silvio Danese, Raja Atreya, Burkhard Pieper, Peyrin-Biroulet, L, Danese, S, Cummings, F, Atreya, R, Greveson, K, Pieper, B, and Kang, T
- Subjects
medicine.medical_specialty ,Anti-Inflammatory Agents ,MEDLINE ,Drug Costs ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Patient-Centered Care ,Adalimumab ,Humans ,Medicine ,Intensive care medicine ,Biosimilar Pharmaceuticals ,Patient Care Team ,Crohn's disease ,Patient care team ,Hepatology ,Tumor Necrosis Factor-alpha ,business.industry ,Gastroenterology ,Antibodies, Monoclonal ,Biosimilar ,Inflammatory Bowel Diseases ,medicine.disease ,Infliximab ,Early Diagnosis ,Patient centric ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Tumor necrosis factor alpha ,Drug Monitoring ,business ,medicine.drug - Abstract
Introduction: The purpose of this review is to highlight the role of biosimilars in early treatment in IBD and introduce ways to facilitate a patient-centric switching process through multi...
- Published
- 2019
179. Microstructure and phase transformation on milled and unmilled Ti induced by water quenching.
- Author
-
Bolokang, A. S., Phasha, M. J., Motaung, D. E., Cummings, F. R., Muller, T. F. G., and Arendse, C. J.
- Subjects
- *
MICROSTRUCTURE , *PHASE transitions , *TITANIUM , *QUENCHING (Chemistry) , *WATER , *TWINNING (Crystallography) , *X-ray diffraction - Abstract
Water quenching of unmilled Ti compact has yielded martensitic-type laths and fishbone-type twinned microstructures, with α', α'' and FCC phases induced. Upon quenching 30 h milled and (0+30) h mixed powders at 1200 °C, α', FCC, tetragonal and BCC phases were detected using XRD. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
180. TACI: a code for interactive analysis of neutron data produced by a tissue equivalent proportional counter
- Author
-
Cummings, F
- Published
- 1984
- Full Text
- View/download PDF
181. Measurement of neutron dose and spectra at light-water reactors
- Author
-
Cummings, F
- Published
- 1982
182. An automated beta irradiator
- Author
-
Cummings, F
- Published
- 1988
183. On spontaneous emission
- Author
-
Cummings, F
- Published
- 1988
- Full Text
- View/download PDF
184. INELASTIC SCATTERING OF ELECTRONS IN GERMANIUM
- Author
-
Cummings, F
- Published
- 1962
- Full Text
- View/download PDF
185. DE-EXCITATION OF MOLECULAR VIBRATION BY COLLISION
- Author
-
Cummings, F
- Published
- 1962
- Full Text
- View/download PDF
186. THE EXACT SOLUTION OF N TWO-LEVEL SYSTEMS INTERACTING WITH A SINGLE-MODE, QUANTIZED RADIATION FIELD.
- Author
-
Cummings, F
- Published
- 1967
- Full Text
- View/download PDF
187. ASPECTS OF A MODEL OF SUPERFLUIDITY.
- Author
-
Cummings, F
- Published
- 1968
- Full Text
- View/download PDF
188. A PROPOSAL FOR AN EXPERIMENTAL DETERMINATION OF THE EQUILIBRIUM CONDENSATE FRACTION IN SUPERFLUID HELIUM.
- Author
-
Cummings, F
- Published
- 1970
- Full Text
- View/download PDF
189. Lessons from shelter homes that help children in especially difficult circumstances: case studies in northern Mexico
- Author
-
Gonzalez Ponce, Sandra M., Cebotarev, Eleanora, and Cummings, F. Harry
- Subjects
shelter homes ,Children in Especially Difficult Circumstances ,experiences ,Casas Hogares ,routines - Abstract
This paper examines issues surrounding shelters (Casas Hogares) that help Children in Especially Difficult Circumstances (CEDC). The literature states that there is a need to "systematically document and learn more from the current efforts in helping children in order to improve program effectiveness at both the country and regional levels" (UNICEF, 1990). This research addresses the aforementioned concern and provides information on what can be learned from the children that live in these shelters, how these shelters function, and what can be learned by studying the experience of these shelters. The investigation was conducted at two shelter homes that help CEDC in a border town in Mexico's north. Interviews and participant observation techniques were used. A total of eighteen staff members were interviewed, and information for over 100 children was acquired. The information on the children was obtained through interviews as well as by asking staff members about the child's particular case. Documenting the routines and the experiences of these shelters, provides valuable lessons that can be taken into consideration for those who wish to work with CEDC. Amongst some of the issues that arose in this study were reasons why children arrive at the shelter home, as well as some of the challenges these organizations face; for example, when dealing with donors and when trying to obtain funds.
- Published
- 2001
190. Switching from intravenous to subcutaneous infliximab maintenance therapy in inflammatory bowel disease: Post hoc longitudinal analysis of a randomized trial.
- Author
-
Schreiber S, D'Haens G, Cummings F, Irving PM, Ye BD, Ben-Horin S, Kim DH, Jeong AL, and Reinisch W
- Subjects
- Humans, Female, Male, Injections, Subcutaneous, Adult, Longitudinal Studies, Middle Aged, Crohn Disease drug therapy, Administration, Intravenous, Colitis, Ulcerative drug therapy, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal pharmacokinetics, Maintenance Chemotherapy, Treatment Outcome, Drug Substitution, Leukocyte L1 Antigen Complex analysis, Infliximab administration & dosage, Infliximab pharmacokinetics, Infliximab therapeutic use, Gastrointestinal Agents administration & dosage, Gastrointestinal Agents pharmacokinetics
- Abstract
Background: Pharmacokinetic non-inferiority of subcutaneous (SC) to intravenous (IV) CT-P13 maintenance therapy was demonstrated in a randomized trial (NCT02883452). This post hoc analysis evaluated longitudinal clinical outcomes with the two infliximab treatment strategies., Methods: Patients with Crohn's disease or ulcerative colitis received CT‑P13 IV loading doses (5 mg/kg; Week [W] 0 and W2) before randomization (1:1) to receive CT-P13 SC (body weight-based dosing every 2 weeks [Q2W]; W6-54; 'SC maintenance group') or CT‑P13 IV (5 mg/kg Q8W; W6-22) then CT-P13 SC (Q2W; W30-54; 'IV-to-SC switch group'). Paired W30/W54 patient-level data were analyzed., Results: Fifty-three (IV-to-SC switch) and fifty-nine (SC maintenance) patients were analyzed. Median trough serum CT-P13 concentrations were significantly higher at W54 versus W30 in the IV-to-SC switch group (20.4 versus 2.3 µg/mL; p < 0.00001), while remaining consistent in the SC maintenance group. Statistically significant improvements in pharmacokinetics, efficacy, fecal calprotectin levels, and quality of life were seen following switch to SC administration at W30 in the IV-to-SC switch group; safety findings were similar pre- and post-switch., Conclusion: Formulation switching from IV to SC infliximab maintenance therapy was well tolerated and may provide additional clinical improvements. Findings require confirmation in larger prospective studies., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
191. Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans.
- Author
-
Li Y, Ramírez-Suástegui C, Harris R, Castañeda-Castro FE, Ascui G, Pérez-Jeldres T, Diaz A, Morong C, Giles DA, Chai J, Seumois G, Sanchez-Elsner T, Cummings F, Kronenberg M, and Vijayanand P
- Subjects
- Humans, Animals, Mice, CD8-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes immunology, Proto-Oncogene Proteins c-bcl-6 metabolism, Proto-Oncogene Proteins c-bcl-6 genetics, Stem Cells immunology, Stem Cells metabolism, Female, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Mice, Knockout, Colon immunology, Colon pathology, Male, Mice, Inbred C57BL, Adoptive Transfer, Disease Models, Animal, Adult, Middle Aged, Colitis, Ulcerative immunology, Colitis, Ulcerative pathology, Hepatocyte Nuclear Factor 1-alpha metabolism, Hepatocyte Nuclear Factor 1-alpha genetics
- Abstract
To understand the role of T cells in the pathogenesis of ulcerative colitis (UC), we analyzed colonic T cells isolated from patients with UC and controls. Here we identified colonic CD4
+ and CD8+ T lymphocyte subsets with gene expression profiles resembling stem-like progenitors, previously reported in several mouse models of autoimmune disease. Stem-like T cells were increased in inflamed areas compared to non-inflamed regions from the same patients. Furthermore, TCR sequence analysis indicated stem-like T cells were clonally related to proinflammatory T cells, suggesting their involvement in sustaining effectors that drive inflammation. Using an adoptive transfer colitis model in mice, we demonstrated that CD4+ T cells deficient in either BCL-6 or TCF1, transcription factors that promote T cell stemness, had decreased colon T cells and diminished pathogenicity. Our results establish a strong association between stem-like T cell populations and UC pathogenesis, highlighting the potential of targeting this population to improve clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2024
- Full Text
- View/download PDF
192. A randomised, crossover trial exploring the patient perspective and effectiveness of biosimilar adalimumab transition: IBD reference and biosimilar adalimumab cross over study (iBaSS).
- Author
-
Young D, Harris C, Rahmany S, Iria I, Gonçalves J, Addison J, Harvey J, Latter S, and Cummings F
- Abstract
Background: Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar medicines, little is known about the patient perspective of transition., Aim: The aim of this study was to investigate clinical outcomes and patient experience of transitioning between reference adalimumab and a biosimilar (SB5)., Method: iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn's disease. Participants, stable on adalimumab before consent, received 24 weeks of treatment with both reference adalimumab and SB5. The primary outcome was the proportion of patients maintaining baseline clinical status throughout each treatment period, with patients' perspective of disease control and treatment satisfaction assessed as secondary outcomes., Results: A total of 112 participants, representative of the heterogeneous patient populations encountered in routine clinical practice, were enrolled. A similar proportion of participants maintained baseline clinical status through each treatment period: 81.8% with reference adalimumab and 79.5% with SB5. Patient reported outcomes (IBD-Control questionnaire (SB5: 15.5; reference adalimumab 15) and TSQM), adverse events and therapeutic drug monitoring remained consistent through both treatment periods, although a higher median injection pain VAS score was noted with SB5 (53/100 versus 6/100 with reference adalimumab). The number of switches undertaken in the study did not impact serum drug concentration or immunogenicity., Conclusion: This study, mimicking real world adalimumab transition, demonstrates that patients undertaking brand transition can be expected to have consistent clinical and satisfaction outcomes., Clinical Trial Registered With Eudract: Number 2018-004967-30., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Published
- 2024
- Full Text
- View/download PDF
193. Establishing key performance indicators for inflammatory bowel disease in the UK.
- Author
-
Quraishi MN, Dobson E, Ainley R, Din S, Wakeman R, Cummings F, Sebastian S, Bloom S, Limdi JK, Dhar A, Speight RA, Bodger K, Kennedy NA, Lamb CA, Arnott ID, and Selinger CP
- Abstract
Background and Aims: Healthcare quality improvement (QI) is the systematic process to continuously improve the quality of care and outcomes for patients. The landmark Inflammatory Bowel Disease (IBD) UK National Audits provided a means to measure the variation in care, highlighting the need to define the standards of excellence in IBD care. Through a consensus approach, we aimed to establish key performance indicators (KPIs), providing reliable benchmarks for IBD care delivery in UK., Methods: KPIs that measure critical aspects of a patient journey within an IBD service were identified though stakeholder meetings. A two-stage Delphi consensus was then conducted. The first involved a multidisciplinary team of IBD clinicians and patients to refine definitions and methodology. The second stage assessed feasibility and utility of the proposed QI process by surveying gastroenterology services across UK., Results: First, the four proposed KPIs were refined and included time from primary care referral to diagnosis in secondary care, time to treatment recommendation following a diagnosis, appropriate use of steroids and advanced therapies prescreening and assessment. Second, the Delphi consensus reported >85% agreement on the feasibility of local adoption of the QI process and >75% agreement on the utility of benchmarking of the KPIs., Conclusions: Through a structured approach, we propose quantifiable KPIs for benchmarking to improve and reduce the individual variation in IBD care across the UK., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
194. Subcutaneous Infliximab Monotherapy Versus Combination Therapy with Immunosuppressants in Inflammatory Bowel Disease: A Post Hoc Analysis of a Randomised Clinical Trial.
- Author
-
D'Haens G, Reinisch W, Schreiber S, Cummings F, Irving PM, Ye BD, Kim DH, Yoon S, and Ben-Horin S
- Subjects
- Humans, Infliximab adverse effects, Immunosuppressive Agents adverse effects, Treatment Outcome, Gastrointestinal Agents adverse effects, Biosimilar Pharmaceuticals therapeutic use, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases chemically induced
- Abstract
Background and Objective: Whether benefits and risks of intravenous (IV) infliximab combotherapy with immunosuppressants versus infliximab monotherapy apply to subcutaneous (SC) infliximab is unknown. This post hoc analysis of a pivotal randomised CT-P13 SC 1.6 trial aimed to compare SC infliximab monotherapy with combotherapy in inflammatory bowel disease (IBD)., Methods: Biologic-naïve patients with active Crohn's disease or ulcerative colitis received CT-P13 IV 5 mg/kg at Week (W) 0 and 2 (dose-loading phase). At W6, patients were randomised (1:1) to receive CT-P13 SC 120 or 240 mg (patients < 80 or ≥ 80 kg) every 2 weeks until W54 (maintenance phase), or to continue CT-P13 IV every 8 weeks until switching to CT-P13 SC from W30. The primary endpoint-non-inferiority of trough serum concentrations-was assessed at W22. We report a post hoc analysis comparing pharmacokinetic, efficacy, safety and immunogenicity outcomes up to W54 for patients randomised to CT-P13 SC, stratified by concomitant immunosuppressant use., Results: Sixty-six patients were randomised to CT-P13 SC (37 monotherapy, 29 combotherapy). At W54, there were no significant differences in the proportions of patients achieving target exposure (5 µg/mL; 96.6% monotherapy vs 95.8% combotherapy; p > 0.999) or meeting efficacy or biomarker outcomes including clinical remission (62.9% vs 74.1%; p = 0.418). Monotherapy and combotherapy groups had comparable immunogenicity (anti-drug antibodies [ADAs]: 65.5% vs 48.0% [p = 0.271], neutralising antibodies [in ADA-positive patients]: 10.5% vs 16.7% [p = 0.630], respectively)., Conclusions: Pharmacokinetics, efficacy and immunogenicity were potentially comparable between SC infliximab monotherapy and combotherapy in biologic-naïve IBD patients., Trial Registration: ClinicalTrials.gov: NCT02883452., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
195. Patient perspectives of successful adalimumab biosimilar transitioning in Crohn's disease: an interview study.
- Author
-
Young D, Cummings F, and Latter S
- Abstract
Objectives: Transition from originator biological medicines to their biosimilar equivalents is now part of routine clinical practice, but there is little understanding of patient experiences, which influence adherence and overall satisfaction with care. Understanding this will help ensure future switches adequately address patients' concerns and expectations leading to better outcomes for all stakeholders., Method: 35 patients participating in a clinical trial including an open-label transition event from originator to biosimilar adalimumab, mimicking what would be encountered in a real-world setting, took part in semi-structured interviews exploring their experience of biosimilar transition., Results: Opinions expressed were often heterogeneous, but common experiences and themes were identified. Five themes were identified following thematic analysis. (1) Understanding and awareness of biosimilars: prior awareness of biosimilars and knowledge of the biosimilar concept was low, indicating a disparity between healthcare professionals and patients. (2) Motivation to undertake transition: patients accept a biosimilar transition to minimise drug expenditure. (3) Initial concerns: before undertaking biosimilar transition away from the brand they had experienced, anticipated loss of efficacy and adverse effects from the biosimilar were common concerns for patients. (4) Reassuring factors: trust in the healthcare team is critical to patient acceptance of biosimilars. Important reassurances include a point of contact, education about biosimilars and monitoring. (5) Experiences during the transition: on reflection, participants described consistent efficacy and tolerability (although 22 participants specifically mentioned injection pain) following brand transition., Conclusion: The majority of patients felt comfortable with future transition to another adalimumab biosimilar. Injection experience was an important component of patient satisfaction., Competing Interests: Competing interests: FC has served as consultant, advisory board member, or speaker for AbbVie, Amgen, Celltrion, Falk, Ferring, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Sandoz, Biogen, Samsung, Takeda, Bristol Myers Squibb and Galapagos. He has received research funding from Biogen, Amgen, Hospira/Pfizer, Celltrion, Janssen, GSK and AZ. SL has received funding for speaking at a symposium sponsored by MSD. DY has received support for travel, accommodation and conference attendance from Sandoz., (© European Association of Hospital Pharmacists 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
- Full Text
- View/download PDF
196. Preparation of biological monolayers for producing high-resolution scanning electron micrographs.
- Author
-
Mentor S, Cummings F, and Fisher D
- Subjects
- Animals, Carbon, Gold, Mice, Microscopy, Electron, Scanning, Electrons, Endothelial Cells
- Abstract
Scanning electron microscopy (SEM) provides a technical platform for nanoscopic mapping of biological structures. Correct preparation of SEM samples can provide an unprecedented understanding of the nexus between cellular morphology and topography. This comparative study critically examines two coating methods for preparing biological samples for scanning electron microscopy, while also providing novel advice on how to prepare in vitro epithelial or endothelial samples for high-resolution scanning-electron microscopy (HR-SEM). Two obstacles often confront the biologist when investigating cellular structures grown under tissue culture conditions, namely., how to prepare and present the biological samples to the HR-SEM microscope without affecting topographical membrane and cellular structural alterations. Firstly, our use of the Millicell cellulose inserts on which to grow our cellular samples in preparation for HR-SEM is both novel and advantageous to comparing the permeability function of cells to their morphological function. Secondly, biological material is often non-conducting, thermally sensitive and fragile and, therefore, needs to be fixed correctly and coated with thin conducting metal to ensure high-resolution detail of samples. Immortalized mouse brain endothelial cells (bEnd5) was used as a basis for describing the preferences in the use of the protocol. We compare two biological sample coating modalities for the visualizing and analysis of texturized, topographical, membranous ultrastructures of brain endothelial cell (BEC) confluent monolayers, namely, carbon and gold:palladium (Au:Pd) sputter coating in preparation for HR-SEM. BEC monolayers sputter-coated with these two modalities produced three-dimensional micrographs which have distinctly different topographical detail from which the nanostructural cellular data can be examined. The two coating methods display differences in the amount of nanoscopic detail that could be resolved in the nanosized membrane cytoarchitecture of BEC monolayers. The micrographical data clearly showed that Au:Pd sputter-coated samples generate descript imagery, providing useful information for profiling membrane nanostructures compared to carbon-coated samples. The recommendations regarding the contrast in two modalities would provide the necessary guidance to biological microscopists in preparing tissue culture samples for HR-SEM., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
- Full Text
- View/download PDF
197. Impact of direct-access IBD physician delivered endoscopy on clinical outcomes: a pre-implementation and post-implementation study.
- Author
-
Stammers M, Rahmany S, Downey L, Borca F, Harris C, Harris R, McDonnell M, Sartain S, Coleman N, Stacey B, Smith TR, Cummings F, Felwick R, and Gwiggner M
- Abstract
Introduction: Patients with suspected inflammatory bowel disease (IBD) referred from primary care often face diagnostic and treatment delays. This study aimed to compare a novel direct-access IBD endoscopy pathway with the traditional care model., Method: Single centre real-world study analysing primary care referrals with suspected IBD. Group A: patients triaged to direct-access IBD endoscopy. Group B: patients undergoing traditional outpatient appointments before the availability of direct-access IBD endoscopy. Demographics, fecal calprotectin (FCP), C-reactive protein (CRP), disease activity score, endoscopy findings, treatment and follow-up were collected and statistically analysed. Ranked semantic analysis of IBD symptoms contained within referral letters was performed., Results: Referral letters did not differ significantly in Groups A and B. Demographic data, FCP and CRP values were similar. Referral to treatment time (RTT) at the time of IBD endoscopy was reduced from 177 days (Group B) to 24 days (Group A) (p<0.0001). Diagnostic yield of IBD was 35.6% (Group B) versus 62.0% (Group A) (p=0.0003). 89.2% of patients underwent colonoscopy in Group B versus 46.4% in Group A. DNA rates were similar in both groups. The direct to IBD endoscopy pathway saved 100% of initial IBD consultant clinics with a 2.5-fold increase in IBD nurse-led follow-up., Conclusion: Our novel pathway resulted in an 86% reduction in RTT with associated increased diagnostic yield while saving 100% of initial IBD consultant outpatient appointments. Replication in other trusts may improve patient experience and accelerate time to diagnosis/treatment while optimising the use of healthcare resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
- Full Text
- View/download PDF
198. Chemical Vapor Deposited Mixed Metal Halide Perovskite Thin Films.
- Author
-
Magubane SS, Arendse CJ, Ngqoloda S, Cummings F, Mtshali C, and Bolokang AS
- Abstract
In this article, we used a two-step chemical vapor deposition (CVD) method to synthesize methylammonium lead-tin triiodide perovskite films, MAPb
1-x Snx I3 , with x varying from 0 to 1. We successfully controlled the concentration of Sn in the perovskite films and used Rutherford backscattering spectroscopy (RBS) to quantify the composition of the precursor films for conversion into perovskite films. According to the RBS results, increasing the SnCl2 source amount in the reaction chamber translate into an increase in Sn concentration in the films. The crystal structure and the optical properties of perovskite films were examined by X-ray diffraction (XRD) and UV-Vis spectrometry. All the perovskite films depicted similar XRD patterns corresponding to a tetragonal structure with I4cm space group despite the precursor films having different crystal structures. The increasing concentration of Sn in the perovskite films linearly decreased the unit volume from about 988.4 Å3 for MAPbI3 to about 983.3 Å3 for MAPb0 .39 Sn0 .61 I3 , which consequently influenced the optical properties of the films manifested by the decrease in energy bandgap (Eg ) and an increase in the disorder in the band gap. The SEM micrographs depicted improvements in the grain size (0.3-1 µm) and surface coverage of the perovskite films compared with the precursor films.- Published
- 2021
- Full Text
- View/download PDF
199. Food-related quality of life is impaired in inflammatory bowel disease and associated with reduced intake of key nutrients.
- Author
-
Whelan K, Murrells T, Morgan M, Cummings F, Stansfield C, Todd A, Sebastian S, Lobo A, Lomer MCE, Lindsay JO, and Czuber-Dochan W
- Subjects
- Adolescent, Adult, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, United Kingdom, Young Adult, Eating psychology, Food adverse effects, Inflammatory Bowel Diseases pathology, Inflammatory Bowel Diseases psychology, Quality of Life
- Abstract
Background: Inflammatory bowel disease (IBD) may impact the extent to which food, eating, and drinking bring satisfaction and enjoyment to peoples' lives, and this may impact dietary intake. The prevalence of an impaired food-related quality of life (FR-QoL), its associated factors, and its impact on diet have not been explored., Objectives: To measure the prevalence and nature of the burden of impaired FR-QoL in people with IBD, the factors associated with these, and their associations with nutrient intake., Methods: We recruited 1576 outpatients with IBD (≥16 years old) in person from 7 IBD centers across the United Kingdom. Patients completed validated questionnaires to measure their FR-QoL, quality of life (QoL), distress, fatigue, anxiety, and depression. Dietary intake was recorded using the European Prospective Investigation into Cancer FFQ. A health professional recorded disease activity, Montreal classification, blood results, BMI, and malnutrition risk. FR-QoL was regressed onto explanatory variables using univariable and multivariable analyses., Results: Data from 1221 patients were available (77.4% response; Crohn's disease, 65%; ulcerative colitis, 35%). The FR-QoL mean (± SD) score was 80.8 ± 26.9, with wide ranges (minimum, 29; maximum, 145). Following multivariable regression, the strongest associations with FR-QoL were the number of recent disease flares (5 flares β = -12.7; P < 0.001), the IBD-specific QoL (β = 0.33; P < 0.001), and IBD-related distress (β = -0.26; P < 0.001). Patients with poorer FR-QoL had lower intakes of fiber (nonstarch polysaccharide; Q1 to Q5 difference = 2.1 g/d; 95% CI: 0.4-3.8; P = 0.048), calcium (192.6 mg/d; 95% CI: 112.5-272.6; P < 0.001), phosphorus (167 mg/d; 95% CI: 58-276; P = 0.041), and magnesium (34.4 mg/d; 95% CI: 9.3-59.4; P = 0.041)., Conclusions: Impaired FR-QoL is prevalent in IBD and is associated with recurrent disease flares, a reduced IBD-specific QoL, and greater IBD-related distress. A poorer FR-QoL was associated with lower intakes of key nutrients of importance to IBD, including those relating to gut health and bone mineralization., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
- Published
- 2021
- Full Text
- View/download PDF
200. Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters.
- Author
-
Kim H, Alten R, Cummings F, Danese S, D'Haens G, Emery P, Ghosh S, Gilletta de Saint Joseph C, Lee J, Lindsay JO, Nikiphorou E, Parker B, Schreiber S, Simoens S, Westhovens R, Jeong JH, and Peyrin-Biroulet L
- Subjects
- Administration, Intravenous, Animals, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal economics, Antibodies, Monoclonal pharmacokinetics, Biosimilar Pharmaceuticals adverse effects, Biosimilar Pharmaceuticals economics, Biosimilar Pharmaceuticals pharmacokinetics, Cost-Benefit Analysis, Diffusion of Innovation, Drug Compounding, Drug Costs, Humans, Infliximab adverse effects, Infliximab economics, Infliximab pharmacokinetics, Injections, Subcutaneous, Antibodies, Monoclonal administration & dosage, Biosimilar Pharmaceuticals administration & dosage, Drug Development economics, Infliximab administration & dosage
- Abstract
The biosimilar concept is now well established. Clinical data accumulated pre- and post-approval have supported biosimilar uptake, in turn stimulating competition in the biologics market and increasing patient access to biologics. Following technological advances, other innovative biologics, such as "biobetters" or "value-added medicines," are now reaching the market. These innovative biologics differ from the reference product by offering additional clinical or non-clinical benefits. We discuss these innovative biologics with reference to CT-P13, initially available as an intravenous (IV) biosimilar of reference infliximab. A subcutaneous (SC) formulation, CT-P13 SC, has now been developed. Relative to CT-P13 IV, CT-P13 SC offers clinical benefits in terms of pharmacokinetics, with comparable efficacy, safety, and immunogenicity, as well as increased convenience for patients and reduced demands on healthcare system resources. As was once the case for biosimilars, nomenclature and regulatory pathways for innovative biologics require clarification to support their uptake and ultimately benefit patients.
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.