Institution
Leicester Royal Infirmary
Healthcare•Leicester, United Kingdom•
About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.
Papers published on a yearly basis
Papers
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TL;DR: A review of pilot studies and trials with a cancer chemoprevention‐related rationale, in which either healthy individuals or patients with premalignant conditions or cancer received polyphenolic phytochemicals is presented.
Abstract: Epidemiological and preclinical evidence suggests that polyphenolic phytochemicals exemplified by epigallocatechin gallate from tea, curcumin from curry and soya isoflavones possess cancer chemopreventive properties. Whilst such naturally occurring polyphenols have been the subject of numerous mechanistic studies in cells, information on their clinical properties, which might help assess their promise as human cancer chemopreventive agents, is scarce. Therefore, we present a review of pilot studies and trials with a cancer chemoprevention-related rationale, in which either healthy individuals or patients with premalignant conditions or cancer received polyphenolic phytochemicals. The review identifies trial design elements specifically applicable to polyphenolic phytochemicals. The available evidence for tea polyphenols tentatively supports their advancement into phase III clinical intervention trials aimed at the prevention of progression of prostate intraepithelial neoplasia, leukoplakia or premalignant cervical disease. In the case of curcumin and soya isoflavones more studies in premalignacies seem appropriate to optimise the nature and design of suitable phase III trials. The abundance of flavonoids and related polyphenols in the plant kingdom makes it possible that several hitherto uncharacterised agents with chemopreventive efficacy are still to be identified, which may constitute attractive alternatives to currently used chemopreventive drugs.
384 citations
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University of Erlangen-Nuremberg1, University of Würzburg2, St James's University Hospital3, University Medical Center Groningen4, University of Düsseldorf5, United Arab Emirates University6, Radboud University Nijmegen Medical Centre7, University Hospital of Wales8, University of California, San Francisco9, Sapienza University of Rome10, Katholieke Universiteit Leuven11, Leicester Royal Infirmary12, Saint Joseph University13, University of Cambridge14, Praxis15, King's College London16, Great Ormond Street Hospital17, University of Amsterdam18, University College London19
TL;DR: Using genetic linkage analysis, the authors found that mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II) in 25 patients.
Abstract: Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss-of-function mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II) in 25 patients. Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence. Absence of PCNT results in disorganized mitotic spindles and missegregation of chromosomes. Mutations in related genes are known to cause primary microcephaly (MCPH1, CDK5RAP2, ASPM, and CENPJ).
377 citations
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TL;DR: The review strongly suggests chemoradiation improves overall survival and progression free survival and reduces local and distant recurrence suggesting concomitant chemotherapy may afford cytotoxic and sensitisation effects.
Abstract: Background
The National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials (RCTs).
Objectives
To review all known RCTs comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer.
Search methods
We searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched.
Selection criteria
This review includes RCTs in cervical cancer comparing concomitant chemoradiation with radiotherapy in the experimental arm. Trials allowing further adjuvant chemotherapy or hydroxyurea were included. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded.
Data collection and analysis
Two authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. Few trials reported acute toxicity adequately, but where possible ORs were calculated for the main types and severities of acute toxicity. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Late toxicity was rarely described in sufficient detail so could only be reviewed qualitatively.
Main results
The original review was based on nineteen trials (17 published and two unpublished) including 4580 patients. This update includes twenty four trials (21 published, 3 unpublished) and 4921 patients, although due to patient exclusion and differential reporting 61% to 75% were available for the analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether or not platinum was used with absolute benefits of 10% and 13% respectively. There was, however, statistical heterogeneity for these outcomes. There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for local recurrence and a suggestion of a benefit for distant recurrence. Acute haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Late effects of treatment were not well reported and so the impact of chemoradiation on these effects could not be determined adequately. Treatment-related deaths were rare.
Authors' conclusions
Concomitant chemoradiation appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also appears to reduce local and distant recurrence suggesting concomitant chemotherapy may afford radiosensitisation and systemic cytotoxic effects. Some acute toxicity is increased, but the long-term side effects are still not clear.
373 citations
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TL;DR: It is confirmed that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.
371 citations
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TL;DR: The time elapsed between injury and operation should be minimised for patients in need of urgent surgical bleeding control, and patients presenting with haemorrhagic shock and an identified source of bleeding should undergo immediate surgical bleed control unless initial resuscitation measures are successful.
Abstract: Introduction
Evidence-based recommendations can be made with respect to many aspects of the acute management of the bleeding trauma patient, which when implemented may lead to improved patient outcomes.
368 citations
Authors
Showing all 5314 results
Name | H-index | Papers | Citations |
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George Davey Smith | 224 | 2540 | 248373 |
Nilesh J. Samani | 149 | 779 | 113545 |
Peter M. Rothwell | 134 | 779 | 67382 |
John F. Thompson | 132 | 1420 | 95894 |
James A. Russell | 124 | 1024 | 87929 |
Paul Bebbington | 119 | 583 | 46341 |
John P. Neoptolemos | 112 | 648 | 52928 |
Richard C. Trembath | 107 | 368 | 41128 |
Andrew J. Wardlaw | 92 | 311 | 33721 |
Melanie J. Davies | 89 | 814 | 36939 |
Philip Quirke | 89 | 378 | 34071 |
Kenneth J. O'Byrne | 87 | 629 | 39193 |
David R. Jones | 87 | 707 | 40501 |
Keith R. Abrams | 86 | 355 | 30980 |
Martin J. S. Dyer | 85 | 373 | 24909 |