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Institution

Guy's and St Thomas' NHS Foundation Trust

HealthcareLondon, United Kingdom
About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.


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Journal ArticleDOI
TL;DR: Aliment Pharmacol Ther 2010; 32: 119–130.
Abstract: Aliment Pharmacol Ther 2010; 32: 119–130 Summary Background Immunosuppression is a risk factor for carcinogenesis. Thiopurines specifically contribute to this. As thiopurines are used more aggressively in the treatment of IBD, it is likely that we will see more thiopurine-related malignancy. Aim To review the literature, exploring how immunosuppression, thiopurines specifically, might cause cancer and which malignancies occur in practice, placing specific emphasis on IBD cohorts. Methods Search terms included ‘malignancy’‘cancer’‘azathioprine’‘mercaptopurine’‘tioguanine (thioguanine)’‘thiopurine’ and ‘inflammatory bowel disease’‘Crohn’s disease’‘ulcerative colitis’. We also searched for specific cancers (lymphoma, colorectal cancer, skin cancer, cervical cancer) and reviewed the reference lists of the articles detected. Results Immunosuppression is associated with an increased risk of cancer. Thiopurines are associated with specific additional risks. In IBD cohorts, very few thiopurine-related malignancies have been reported. However, studies suggest a relative risk of 4–5 for lymphoma. This still translates into a low actual risk, (one extra lymphoma in every 300–1400 years of thiopurine treatment). Conclusions Whilst we must be aware of this risk and counsel our patients appropriately, thiopurines remain a mainstay of IBD therapy. We present practical advice aimed at minimizing our patients’ risk of developing malignancy, whilst optimizing the benefits that thiopurines can provide.

88 citations

Journal ArticleDOI
TL;DR: Clinoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation, suggesting that these antibodies may mediate the white matter disease.
Abstract: Objective: To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders. Method: Ten children with significant white matter involvement, with or without anti-NMDAR encephalitis, were identified from 46 consecutive NMDAR antibody–positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated. Results: Three distinct clinicoradiologic phenotypes were recognized: brainstem encephalitis (n 5 3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE) (n 5 2), and acquired demyelination syndromes (ADS) (n5 5); 3 of the 5 with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Typical NMDAR antibody encephalitis was seen in 3 patients remote from the first neurologic syndrome (2 brainstem, 1 post-HSVE). Six of the 7 patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titers. Conclusion: Clinicoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR antibody levels, suggesting that these antibodies may mediate the white matter disease. Neurol Neuroimmunol Neuroinflammation 2014;1:e2; doi:

88 citations

Journal ArticleDOI
TL;DR: The natural history of multiple sclerosis—a geographically based study, 2: predictive value of the early clinical course, 3: multivariate analysis of predictive factors and models of outcome, and 4: Prediction of outcome in multiple sclerosis based on multivariate models.
Abstract: 1aforearlymultiplesclerosis:CHAMPStrialsubgroup analyses. Ann Neurol. 2002;51:481-490. 42. Hadjimichael O, Vollmer TL. Adherence to injection therapy in multiple sclerosis: patients survey. Neurology. 1999;52:A549. 43. The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: experience during the first three years. Neurology. 1996;47:889-894. 44. Malucchi S, Sala A, Gilli F, et al. Neutralizing antibodies reduce the efficacy of betaIFN during treatment of multiple sclerosis. Neurology. 2004; 62:2031-2037. 45. Rudick RA, Simonian NA, Alam JA, et al. Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis: Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology. 1998;50:1266-1272. 46. Rice G. The significance of neutralizing antibodies inpatientswithmultiplesclerosis treatedwith interferon beta. Arch Neurol. 2001;58:1297-1298. 47. Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis—a geographically based study, 2: predictive value of the early clinical course. Brain. 1989;112:1419-1428. 48. Weinshenker BG, Rice GPA, Noseworthy JH, et al. The natural history of multiple sclerosis—a geographically based study, 3: multivariate analysis of predictive factors and models of outcome. Brain. 1991;114:1045-1056. 49. Runmarker B, Andersson C, Oden A, Andersen O. Prediction of outcome in multiple sclerosis based on multivariate models. J Neurol. 1994;241: 597-604. 50. Confavreux C, Aimard G, Devic M. Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain. 1980;103:281-300.

88 citations

Journal ArticleDOI
21 Sep 2021-JAMA
TL;DR: Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volumeMechanical ventilation did not significantly reduce 90-day mortality, and the study may have been underpowered to detect a clinically important difference.
Abstract: Importance In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%];P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3];P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. Trial Registration ClinicalTrials.gov Identifier:NCT02654327

88 citations

Journal ArticleDOI
TL;DR: Although the primary endpoint was not reached, several signals suggest CBD-rich botanical extract may be beneficial for symptomatic treatment of UC.
Abstract: Background Cannabidiol (CBD) exhibits anti-inflammatory properties that could improve disease activity in inflammatory bowel disease. This proof-of-concept study assessed efficacy, safety and tolerability of CBD-rich botanical extract in ulcerative colitis (UC) patients. Methods Patients aged 18 years or older, with left-sided or extensive UC, Mayo scores of 4-10 (endoscopy scores ≥1), and on stable 5-aminosalicylic acid dosing, were randomized to 10-weeks' CBD-rich botanical extract or placebo capsules. The primary endpoint was the percentage of patients in remission after treatment. Statistical testing was 2-sided, using a 10% significance level. Results Patients were less tolerant of CBD-rich botanical extract compared with placebo, taking on average one-third fewer capsules, and having more compliance-related protocol deviations (principally insufficient exposure), prompting identification of a per protocol (PP) analysis set. The primary endpoint was negative; end of treatment remission rates were similar for CBD-rich botanical extract (28%) and placebo (26%). However, PP analysis of total and partial Mayo scores favoured CBD-rich botanical extract (P = 0.068 and P = 0.038, respectively). Additionally, PP analyses of the more subjective physician's global assessment of illness severity, subject global impression of change, and patient-reported quality-of-life outcomes were improved for patients taking CBD-rich botanical extract (P = 0.069, P = 0.003, and P = 0.065, respectively). Adverse events (AEs) were predominantly mild/moderate with many in the CBD-rich botanical extract group potentially attributable to the ∆9-tetrahydrocannabinol content. A greater proportion of gastrointestinal-related AEs, indicative of UC worsening, was seen on placebo. Conclusion Although the primary endpoint was not reached, several signals suggest CBD-rich botanical extract may be beneficial for symptomatic treatment of UC.

88 citations


Authors

Showing all 7765 results

NameH-indexPapersCitations
Christopher J L Murray209754310329
Bruce M. Psaty1811205138244
Giuseppe Remuzzi1721226160440
Mika Kivimäki1661515141468
Simon I. Hay165557153307
Theo Vos156502186409
Ali H. Mokdad156634160599
Steven Williams144137586712
Igor Rudan142658103659
Mohsen Naghavi139381169048
Christopher D.M. Fletcher13867482484
Martin McKee1381732125972
David A. Jackson136109568352
Graham G. Giles136124980038
Yang Liu1292506122380
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202316
202298
20211,488
20201,123
2019829
2018767