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St George's, University of London

EducationLondon, United Kingdom
About: St George's, University of London is a education organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Health care. The organization has 4953 authors who have published 11675 publications receiving 574153 citations. The organization is also known as: SGUL & St George's Hospital Medical School.


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Journal ArticleDOI
TL;DR: Focusing on the clinical diagnostics setting, this paper is intended to contribute to the discussion and the development of guidelines in this fast-moving field, and provide recommendations for health-care professionals.
Abstract: In recent years, the cost of generating genome information has shown a rapid decline.1, 2 High-throughput genomic technologies make it possible to sequence the whole exome or genome of a person at a price that is affordable for some health-care systems. More services based on these technologies are now becoming available for patients, raising the issue of how to ensure that these are provided appropriately. In order to determine both the clinical utility of genetic testing and assure a high quality of the analysis, the interpretation and communication of the results must be discussed so that patients can receive appropriate advice and genetic testing. The Public and Professional Policy Committee (PPPC) and the Quality Committee of the European Society of Human Genetics (ESHG) addressed these challenges at a joint workshop in Gothenburg, Sweden, in 2010.3 PPPC also organised workshops in Amsterdam, the Netherlands (January 2011 in collaboration with the EU-funded project TECHGENE, January 2012). A report for the Health Council of the Netherlands served as a background document for the PPPC's reflections.4 Focusing on the clinical diagnostics setting, this paper is intended to contribute to the discussion and the development of guidelines in this fast-moving field, and provide recommendations for health-care professionals. The paper and recommendations were posted on the ESHG website from 20 June to 1 August 2012 for comment by the membership. The final version was approved by the ESHG Board in December 2012.

367 citations

Journal ArticleDOI
TL;DR: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline, and working memory may be particularly dependent on complex networks dependent on white matter connections.
Abstract: Background: Damage to white matter tracts, resulting in “cerebral disconnection,” may underlie age-related cognitive decline. Methods: Using diffusion tensor MRI (DTI) to investigate white matter damage, and magnetic resonance spectroscopy (MRS) to look at its underlying pathologic basis, the authors investigated the relationship between white matter structure and cognition in 106 healthy middle-aged and elderly adults. Fractional anisotropy (FA) and mean diffusivity (MD) values, whole brain white matter histograms, and regions of interest placed in the white matter of the centrum semiovale were analyzed. Correlations with executive function, working memory, and information-processing speed were performed. Results: There was a progressive reduction in FA and increase in diffusivity with age in both region of interest (r = 0.551, p r = 0.625, p N -acetyl aspartate, a neuronal marker, with DTI parameters ( r = 0.253, p Conclusion: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline. Working memory may be particularly dependent on complex networks dependent on white matter connections.

365 citations

Journal ArticleDOI
TL;DR: The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high quality teaching and research related to diagnostic imaging in women's healthcare.
Abstract: The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high quality teaching and research related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Com mittee (CSC) has a remit to develop Practice Gui delines and Consensus Statements as educational recommendations that provide healthcare practit ioners with a consensus based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or state ments issued by the CSC. The ISUOG CSC docu ments are not intended to establish a legal stan dard of care because interpretation of the eviden ce that underpins the Guidelines may be influen ced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org).

364 citations

Journal ArticleDOI
TL;DR: A meta-analysis of GWAS studies for asthma from multiancestral cohorts identifies five new loci and finds that the asthma-associated loci are enriched near enhancer marks in immune cells, suggesting a major role of these loci in the regulation of immunologically related mechanisms.
Abstract: We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

363 citations

Journal ArticleDOI
TL;DR: Budesonide increased non-fatal serious adverse pneumonia events compared with placebo, but the effect was less precise and was based on shorter trials (OR 1.78, 95% confidence interval (CI) 1.50 to 2.12; 18 more per 1000 treated over 18 months; high quality).
Abstract: Background Inhaled corticosteroids (ICS) are anti-inflammatory drugs that have proven benefits for people with worsening symptoms of chronic obstructive pulmonary disease (COPD) and repeated exacerbations. They are commonly used as combination inhalers with long-acting beta2-agonists (LABA) to reduce exacerbation rates and all-cause mortality, and to improve lung function and quality of life. The most common combinations of ICS and LABA used in combination inhalers are fluticasone and salmeterol, budesonide and formoterol and a new formulation of fluticasone in combination with vilanterol, which is now available. ICS have been associated with increased risk of pneumonia, but the magnitude of risk and how this compares with different ICS remain unclear. Recent reviews conducted to address their safety have not compared the relative safety of these two drugs when used alone or in combination with LABA. Objectives To assess the risk of pneumonia associated with the use of fluticasone and budesonide for COPD. Search methods We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), clinicaltrials.gov, reference lists of existing systematic reviews and manufacturer websites. The most recent searches were conducted in September 2013. Selection criteria We included parallel-group randomised controlled trials (RCTs) of at least 12 weeks' duration. Studies were included if they compared the ICS budesonide or fluticasone versus placebo, or either ICS in combination with a LABA versus the same LABA as monotherapy for people with COPD. Data collection and analysis Two review authors independently extracted study characteristics, numerical data and risk of bias information for each included study. We looked at direct comparisons of ICS versus placebo separately from comparisons of ICS/LABA versus LABA for all outcomes, and we combined these with subgroups when no important heterogeneity was noted. After assessing for transitivity, we conducted an indirect comparison to compare budesonide versus fluticasone monotherapy, but we could not do the same for the combination therapies because of systematic differences between the budesonide and fluticasone combination data sets. When appropriate, we explored the effects of ICS dose, duration of ICS therapy and baseline severity on the primary outcome. Findings of all outcomes are presented in 'Summary of findings' tables using GRADEPro. Main results We found 43 studies that met the inclusion criteria, and more evidence was provided for fluticasone (26 studies; n = 21,247) than for budesonide (17 studies; n = 10,150). Evidence from the budesonide studies was more inconsistent and less precise, and the studies were shorter. The populations within studies were more often male with a mean age of around 63, mean pack-years smoked over 40 and mean predicted forced expiratory volume of one second (FEV1) less than 50%. High or uneven dropout was considered a high risk of bias in almost 40% of the trials, but conclusions for the primary outcome did not change when the trials at high risk of bias were removed in a sensitivity analysis. Fluticasone increased non-fatal serious adverse pneumonia events (requiring hospital admission) (odds ratio (OR) 1.78, 95% confidence interval (CI) 1.50 to 2.12; 18 more per 1000 treated over 18 months; high quality), and no evidence suggested that this outcome was reduced by delivering it in combination with salmeterol or vilanterol (subgroup differences: I2 = 0%, P value 0.51), or that different doses, trial duration or baseline severity significantly affected the estimate. Budesonide also increased non-fatal serious adverse pneumonia events compared with placebo, but the effect was less precise and was based on shorter trials (OR 1.62, 95% CI 1.00 to 2.62; six more per 1000 treated over nine months; moderate quality). Some of the variation in the budesonide data could be explained by a significant difference between the two commonly used doses: 640 mcg was associated with a larger effect than 320 mcg relative to placebo (subgroup differences: I2 = 74%, P value 0.05). An indirect comparison of budesonide versus fluticasone monotherapy revealed no significant differences with respect to serious adverse events (pneumonia-related or all-cause) or mortality. The risk of any pneumonia event (i.e. less serious cases treated in the community) was higher with fluticasone than with budesonide (OR 1.86, 95% CI 1.04 to 3.34); this was the only significant difference reported between the two drugs. However, this finding should be interpreted with caution because of possible differences in the assignment of pneumonia diagnosis, and because no trials directly compared the two drugs. No significant difference in overall mortality rates was observed between either of the inhaled steroids and the control interventions (both high-quality evidence), and pneumonia-related deaths were too rare to permit conclusions to be drawn. Authors' conclusions Budesonide and fluticasone, delivered alone or in combination with a LABA, are associated with increased risk of serious adverse pneumonia events, but neither significantly affected mortality compared with controls. The safety concerns highlighted in this review should be balanced with recent cohort data and established randomised evidence of efficacy regarding exacerbations and quality of life. Comparison of the two drugs revealed no statistically significant difference in serious pneumonias, mortality or serious adverse events. Fluticasone was associated with higher risk of any pneumonia when compared with budesonide (i.e. less serious cases dealt with in the community), but variation in the definitions used by the respective manufacturers is a potential confounding factor in their comparison. Primary research should accurately measure pneumonia outcomes and should clarify both the definition and the method of diagnosis used, especially for new formulations and combinations for which little evidence of the associated pneumonia risk is currently available. Similarly, systematic reviews and cohorts should address the reliability of assigning 'pneumonia' as an adverse event or cause of death and should determine how this affects the applicability of findings.

362 citations


Authors

Showing all 5006 results

NameH-indexPapersCitations
JoAnn E. Manson2701819258509
Paul M. Ridker2331242245097
George Davey Smith2242540248373
Peer Bork206697245427
Grant W. Montgomery157926108118
Naveed Sattar1551326116368
Alan S. Verkman14677170434
David P. Strachan143472105256
Sekar Kathiresan14147998784
Nick C. Fox13974893036
Andrew Steptoe137100373431
Daniel I. Chasman13448472180
Joel N. Hirschhorn133431101061
Dan M. Roden13285967578
Hugh Watkins12852491317
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202313
202293
20211,153
2020999
2019873
2018789