Institution
University of Southampton
Education•Southampton, United Kingdom•
About: University of Southampton is a education organization based out in Southampton, United Kingdom. It is known for research contribution in the topics: Population & Laser. The organization has 37184 authors who have published 99400 publications receiving 3462915 citations. The organization is also known as: Southampton University & Soton Uni.
Topics: Population, Laser, Context (language use), Optical fiber, Fiber laser
Papers published on a yearly basis
Papers
More filters
••
University of Southampton1, University of Birmingham2, Clatterbridge Cancer Centre NHS Foundation Trust3, University of Liverpool4, University of Leeds5, University Hospitals Birmingham NHS Foundation Trust6, Leeds Teaching Hospitals NHS Trust7, Cambridge University Hospitals NHS Foundation Trust8, University of Bristol9, Weston Park Hospital10, University of Glasgow11, University College Hospital12, Heidelberg University13, University of Edinburgh14, University of Manchester15, University College London16
TL;DR: This randomised, controlled, multicentre, phase 3 study aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer.
Abstract: BACKGROUND
Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy. We aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer.
METHODS
This randomised, controlled, multicentre, phase 3 study was done across 44 specialist hepatopancreatobiliary centres in the UK. Eligible patients were aged 18 years or older and had histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone a macroscopically complete resection (which includes liver resection, pancreatic resection, or, less commonly, both) with curative intent, and an Eastern Cooperative Oncology Group performance status of less than 2. Patients who had not completely recovered from previous surgery or who had previous chemotherapy or radiotherapy for biliary tract cancer were also excluded. Patients were randomly assigned 1:1 to receive oral capecitabine (1250 mg/m twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation commencing within 16 weeks of surgery. Treatment was not masked, and allocation concealment was achieved with a computerised minimisation algorithm that stratified patients by surgical centre, site of disease, resection status, and performance status. The primary outcome was overall survival. As prespecified, analyses were done by intention to treat and per protocol. This study is registered with EudraCT, number 2005-003318-13.
FINDINGS
Between March 15, 2006, and Dec 4, 2014, 447 patients were enrolled; 223 patients with biliary tract cancer resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. The data cutoff for this analysis was March 6, 2017. The median follow-up for all patients was 60 months (IQR 37-60). In the intention-to-treat analysis, median overall survival was 51·1 months (95% CI 34·6-59·1) in the capecitabine group compared with 36·4 months (29·7-44·5) in the observation group (adjusted hazard ratio [HR] 0·81, 95% CI 0·63-1·04; p=0·097). In a protocol-specified sensitivity analysis, adjusting for minimisation factors and nodal status, grade, and gender, the overall survival HR was 0·71 (95% CI 0·55-0·92; p=0·010). In the prespecified per-protocol analysis (210 patients in the capecitabine group and 220 in the observation group), median overall survival was 53 months (95% CI 40 to not reached) in the capecitabine group and 36 months (30-44) in the observation group (adjusted HR 0·75, 95% CI 0·58-0·97; p=0·028). In the intention-to-treat analysis, median recurrence-free survival was 24·4 months (95% CI 18·6-35·9) in the capecitabine group and 17·5 months (12·0-23·8) in the observation group. In the per-protocol analysis, median recurrence-free survival was 25·9 months (95% CI 19·8-46·3) in the capecitabine group and 17·4 months (12·0-23·7) in the observation group. Adverse events were measured in the capecitabine group only, and of the 213 patients who received at least one cycle, 94 (44%) had at least one grade 3 toxicity, the most frequent of which were hand-foot syndrome in 43 (20%) patients, diarrhoea in 16 (8%) patients, and fatigue in 16 (8%) patients. One (<1%) patient had grade 4 cardiac ischaemia or infarction. Serious adverse events were observed in 47 (21%) of 223 patients in the capecitabine group and 22 (10%) of 224 patients in the observation group. No deaths were deemed to be treatment related.
INTERPRETATION
Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting.
FUNDING
Cancer Research UK and Roche.
652 citations
••
TL;DR: A general scheme for practice in Europe could be provided and a set of recommendations for the conceptualisation and management of hyperkinetic disorder and attention deficit/hyperactivity disorder (ADHD) are presented.
Abstract: BACKGROUND: The validity of clinical guidelines changes over time, because new evidence-based knowledge and experience develop OBJECTIVE: Hence, the European clinical guidelines on hyperkinetic disorder from 1998 had to be evaluated and modified METHOD: Discussions at the European Network for Hyperkinetic Disorders (EUNETHYDIS) and iterative critique of each clinical analysis Guided by evidence-based information and based on evaluation (rather than metaanalysis) of the scientific evidence a group of child psychiatrists and psychologists from several European countries updated the guidelines of 1998 When reliable information is lacking the group gives a clinical consensus when it could be found among themselves RESULTS: The group presents here a set of recommendations for the conceptualization and management of hyperkinetic disorder and attention deficit/hyperactivity disorder (ADHD) CONCLUSION: A general scheme for practice in Europe could be provided, on behalf of the European Society for Child and Adolescent Psychiatry (ESCAP)
652 citations
••
Utrecht University1, Yale University2, Rice University3, Purdue University4, Alfred Wegener Institute for Polar and Marine Research5, Stockholm University6, University of Rhode Island7, Brown University8, United States Geological Survey9, University of Bordeaux10, Aix-Marseille University11, Centre national de la recherche scientifique12, Yamagata University13, University College London14, Norwegian Polar Institute15, Boston University16, British Geological Survey17, University of Michigan18, Kyushu University19, University of Southampton20, University of Aberdeen21, University of Padua22, Japan Agency for Marine-Earth Science and Technology23, James Madison University24, University of Tsukuba25, Tohoku University26, National Institute of Advanced Industrial Science and Technology27, Hokkaido University28
TL;DR: It is shown that sea surface temperatures near the North Pole increased from ∼18 °C to over 23°C during this event, which suggests that higher-than-modern greenhouse gas concentrations must have operated in conjunction with other feedback mechanisms—perhaps polar stratospheric clouds or hurricane-induced ocean mixing—to amplify early Palaeogene polar temperatures.
Abstract: The Palaeocene/Eocene thermal maximum, ~55 million years ago, was a brief period of widespread, extreme climatic warming1, 2, 3, that was associated with massive atmospheric greenhouse gas input4. Although aspects of the resulting environmental changes are well documented at low latitudes, no data were available to quantify simultaneous changes in the Arctic region. Here we identify the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence obtained during the Arctic Coring Expedition5. We show that sea surface temperatures near the North Pole increased from ~18 °C to over 23 °C during this event. Such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming. At the same time, sea level rose while anoxic and euxinic conditions developed in the ocean's bottom waters and photic zone, respectively. Increasing temperature and sea level match expectations based on palaeoclimate model simulations6, but the absolute polar temperatures that we derive before, during and after the event are more than 10 °C warmer than those model-predicted. This suggests that higher-than-modern greenhouse gas concentrations must have operated in conjunction with other feedback mechanisms—perhaps polar stratospheric clouds7 or hurricane-induced ocean mixing8—to amplify early Palaeogene polar temperatures.
652 citations
••
University of Southampton1, University of Nottingham2, Newcastle University3, University of London4, University College London5, University Hospital Southampton NHS Foundation Trust6, University of Melbourne7, University of the West Indies8, Agency for Science, Technology and Research9, University of Auckland10
TL;DR: It is proposed that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.
651 citations
••
TL;DR: High specificity estimates suggest that NAAT tests should be the first-line test for ruling in TB meningitis, but that they need to be combined with the result of other tests in order to rule out disease.
Abstract: Objectives To evaluate the effectiveness of available rapid diagnostic tests to identify tuberculosis (TB) infection. Data sources Electronic databases were searched from 1975 to August 2003 for tests for active TB and to March 2004 for tests for latent tuberculosis infection (LTBI). Review methods Studies were selected and evaluated that (1) tested for LTBI, (2) compared tuberculin skin test (TST) and interferon-gamma assays based on ESAT-6 and CFP-10 antigens and (3) provided information on TB exposure or bacille Calmette-Guerin (BCG) vaccination or HIV status. For each test comparison, the sensitivity, specificity and 95% confidence intervals (CIs) were calculated. Sources of heterogeneity were investigated by adding covariates to the standard regression model. The authors examined whether interferon-gamma assays were more strongly associated with high versus low TB exposure than TST. Odds ratios (ORs) were calculated for the association between test results and exposures from each study along with their 95% CIs. Within each study, the OR value for one test was divided by that for another to produce a ratio of OR (ROR). Results A total of 212 studies were included, providing 368 data sets. A further 19 studies assessing fully automated liquid culture were included. Overall, nucleic acid amplification test (NAAT) accuracy was far superior when applied to respiratory samples as opposed to other body fluids. The better quality in-house studies, were, for pulmonary TB, much better at ruling out TB than the commercial tests (higher sensitivity), but were less good at ruling it in (lower specificity), but it is not possible to recommend any one over another owing to a lack of direct test comparisons. The specificity of NAAT tests was high when applied to body fluids, for example for TB meningitis and pleural TB, but sensitivity was poor, indicating that these tests cannot be used reliably to rule out TB. High specificity estimates suggest that NAAT tests should be the first-line test for ruling in TB meningitis, but that they need to be combined with the result of other tests in order to rule out disease. Evidence for NAAT tests in other forms of TB and for phage-based tests is significantly less prolific than for those above and further research is needed to establish accuracy. There is no evidence to support the use of adenosine deaminase (ADA) tests for diagnosis of pulmonary TB; however, there is considerable evidence to support their use for diagnosis of pleural TB and to a slightly lesser extent for TB meningitis. Anti-TB antibody test performance was universally poor, regardless of type of TB. Fully automated liquid culture methods were superior to culture on solid media, in terms of their speed and their precision. In total, 13 studies were included. Assays based on RD1 specific antigens, ESAT-6 or CFP-10, correlate better with intensity of exposure, and therefore are more likely than TST/purified protein derivative (PPD)-based assays to detect LTBI accurately. An additional advantage is that they are more likely to be independent of BCG vaccination status and HIV status. Conclusions The NAAT tests provide a reliable way of increasing the specificity of diagnosis (ruling in disease) but sensitivity is too poor to rule out disease, especially in smear-negative (paucibacillary) disease where clinical diagnosis is equivocal and where the clinical need is greatest. For extra-pulmonary TB, clinical judgement has both poor sensitivity and specificity. For pleural TB and TB meningitis, adenosine deaminase tests have high sensitivity but limited specificity. NAATs have high specificity and could be used alongside ADA (or interferon-gamma) to increase sensitivity for ruling out disease and NAAT for high specificity to rule it in. All studies from low-prevalence countries strongly suggest that the RD1 antigen-based assays are more accurate than TST- and PPD-based assays for diagnosis of LTBI. If their superior diagnostic capability is found to hold up in routine clinical practice, they could confer several advantages on TB control programmes. Further research for active TB needs to establish diagnostic accuracy in a wide spectrum of patients, against an appropriate reference test, and avoiding the major sources of bias. For LTBI, research needs to address different epidemiological and clinical settings, to evaluate the performance of the main existing commercial assays in head-to-head comparison in both developed and developing countries, and to assess the role of adding more TB-specific antigens to try to improve diagnostic sensitivity.
649 citations
Authors
Showing all 37632 results
Name | H-index | Papers | Citations |
---|---|---|---|
Cyrus Cooper | 204 | 1869 | 206782 |
Stephen V. Faraone | 188 | 1427 | 140298 |
David R. Williams | 178 | 2034 | 138789 |
Charles M. Lieber | 165 | 521 | 132811 |
David W. Johnson | 160 | 2714 | 140778 |
Mark E. Cooper | 158 | 1463 | 124887 |
Pete Smith | 156 | 2464 | 138819 |
Joseph Jankovic | 153 | 1146 | 93840 |
Vivek Sharma | 150 | 3030 | 136228 |
David J.P. Barker | 148 | 446 | 99373 |
Debbie A Lawlor | 147 | 1114 | 101123 |
Olli T. Raitakari | 142 | 1232 | 103487 |
Stephen T. Holgate | 142 | 870 | 82345 |
Alexander Belyaev | 142 | 1895 | 100796 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |