Barts Health NHS Trust

About: Barts Health NHS Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 3483 authors who have published 3807 publications receiving 81829 citations.

Chronic obstructive pulmonary disease and exacerbations: Patient insights from the global Hidden Depths of COPD survey

Abstract: Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations. We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population. Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors. The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity. Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation. While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered. A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations. Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD. However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD. To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of exacerbations.

AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): A randomised, double-blind, placebo-controlled, phase II trial.

Abstract: 1007Background: The PI3K/AKT signalling pathway is frequently activated in triple-negative breast cancer (TNBC). AZD5363 is a highly-selective, oral, small molecule AKT inhibitor. The PAKT trial investigated the addition of AZD5363 to paclitaxel as 1st-line therapy for TNBC. Methods: This investigator-led, double-blind, placebo-controlled, randomised phase II trial, recruited women with previously untreated, metastatic TNBC at 42 sites in 6 countries. Patients were randomly assigned (1:1) to paclitaxel 90mg/m2 (days 1, 8, & 15) with either AZD5363 (400mg BD) or placebo (days 2-5, 9-12, 16-19) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), PFS in the subgroup with PIK3CA/AKT1/PTEN-alterations, response, and safety. Results: Between 05/2014 and 06/2017, 140 patients were randomised to paclitaxel + AZD5363 (n = 70) or paclitaxel + placebo (n = 70). Median duration of follow-up was ...

Ethnicity and outcomes in patients hospitalised with COVID-19 infection in East London: an observational cohort study

Abstract: Background Preliminary studies suggest that people from Black, Asian and Minority Ethnic (BAME) backgrounds experience higher mortality from COVID-19 but the underlying reasons remain unclear. Methods Prospective analysis of registry data describing patients admitted to five acute NHS Hospitals in east London, UK for COVID-19. Emergency hospital admissions with confirmed SARS-CoV-2 aged 16 years or over were included. Data, including ethnicity, social deprivation, frailty, patient care and detailed risk factors for mortality, were extracted from hospital electronic records. Multivariable survival analysis was used to assess associations between ethnic group and mortality accounting for the effects of age, sex and various other risk factors. Results are presented as hazard ratios (HR) or odds ratios (OR) with 95% confidence intervals. Findings 1996 adult patients were admitted between 1st March and 13th May 2020. After excluding 259 patients with missing ethnicity data, 1737 were included in our analysis of whom 511 had died by day 30 (29%). 538 (31%) were from Asian, 340 (20%) Black and 707 (40%) white backgrounds. Compared to White patients, those from BAME backgrounds were younger, with differing co-morbidity profiles and less frailty. Asian and Black patients were more likely to be admitted to intensive care and to receive invasive ventilation (OR 1·54, [1·06-2·23]; p=0·023 and 1·80 [1·20-2·71]; p=0·005, respectively). After adjustment for age and sex, patients from Asian (HR 1·49 [1·19-1·86]; p Interpretation Patients from Asian and Black backgrounds are more likely to die from COVID-19 infection despite controlling for all previously identified confounders. Higher rates of invasive ventilation in intensive care indicate greater acute disease severity. Our analyses suggest that patients of Asian and Black backgrounds suffered disproportionate rates of premature death from COVID-19. Funding None Research in context Evidence before this study We searched PubMed, Google Scholar, Medrxiv, Trip Medical Database and internet search engines from inception to May 10th 2020, using the terms “(COVID-19 or 2019-nCoV or SARS-CoV-2) AND (ethnicity)”, with no language restrictions, for research articles, editorials and commentaries. We identified 25 articles. Ten were international opinion pieces, fifteen were research articles reporting analyses of national and cohort datasets, predominantly in the United Kingdom (UK) and United States (US). Each of these studies indicated an increased risk of adverse outcomes in people from BAME backgrounds; either in terms of COVID-19 acquisition, disease severity or mortality. However, the underlying causes were unclear. Aggregated US data determined the relative risk of death for those of Black ethnicity compared to White ethnic groups to be 3.57. Three UK biobank cohort studies, limited by low BAME representation, described ethnicity as an independent risk factor of COVID-19 infection, partially attenuated by socio-economic status (SES). Analysis of a London hospital cohort of 520; experiencing 144 deaths, revealed an age and co-morbidity adjusted mortality odds ratio of 1.72 in Black populations of borderline significance. Age and geographical region-adjusted standardised mortality ratios, derived from UK composite hospital data, emphasised ethnic differences; being 2.41 for Bangladeshis and 3.24 for Black Africans. The impact of gender and deprivation was not explored. Another study of 5683 in-hospital deaths (England alone; 629 (11%) BAME) confirmed increased mortality risks in people from Black and Asian groups only partially attributable to social deprivation and co-morbidity but did not adjust for other vulnerability factors. There remained a need for a more detailed analysis of outcomes across different ethnic groups in a large, high acuity dataset, adjusting for broader clinical and laboratory prognostic factors, alongside SES, smoking status, age, body mass index (BMI) and sex. Added value of this study We conducted a large observational cohort study of COVID-19 hospital admissions within an area which experienced the highest rates of COVID-19 infection and mortality in the UK. It offers detailed insight into a majority (60%) ethnically diverse cohort and adds substantial evidence that ethnicity is a predictor of poor outcomes for COVID-19 patients at, and beyond, 30 days. Using robust multivariable survival analyses we have quantified and described the impact on this association of a number of additional prognostic factors such as frailty score and markers of inflammation alongside age, sex, deprivation, co-morbidity, BMI and smoking status. Those of Asian and Black ethnicities were consistently found to have an increased risk of 30 and 90 day mortality and an increased risk of requiring mechanical ventilation as compared to those of White ethnicity. The peak CRP and D-dimer levels in those of Black ethnicity were significantly higher than those of other ethnicities suggesting that these biological differences may accompany greater disease severity and increased risk of adverse outcomes. Implications of all the available evidence It is clear that ethnicity is a predictor of a positive SARS-CoV2 result, disease severity and mortality, regardless of age, sex, geographical location, deprivation, smoking status, BMI, co-morbidities and frailty. The association appears to be underpinned by a combination of factors including SES, pre-existing health conditions, biological risk factors such as D-dimers, environmental and structural determinants of health; but their relative contribution is unclear. Understanding these drivers is critical to designing interventions and refining clinical and Public Health policies. The evidence also emphasises the need for robust surveillance of ethnicity in health care research.

Paediatric bone and joint infection.

Abstract: Despite advances in understanding and management, paediatric osteoarticular infections continue to pose diagnostic difficulties for clinicians. Delays in diagnosis can lead to potentially devastating morbidity.No single investigation, including joint aspiration, is sufficiently reliable to diagnose conclusively paediatric bone and joint infection. Diagnosis should be based on a combination of clinical signs, imaging and laboratory investigations. Algorithms should supplement, and not replace, clinical decision making in all cases.The roles of aspiration, arthrotomy and arthroscopy in the treatment of septic arthritis are not clearly defined. There is a very limited role for surgery in the management of acute haematogenous osteomyelitis.The ideal duration and mode of administration of antibiotic therapy for osteoarticular paediatric infection is not yet fully defined but there is increasing evidence that shorter courses (three weeks) and early conversion (day four) to oral administration is safe and effective in appropriate cases. Clear and concise antibiotic guidelines should be available based on local population characteristics, pathogens and their sensitivities.Kingella kingae is increasingly identified through polymerase chain reaction and is now recognised as the commonest pathogen in children aged under four years. Methicillin-resistant Staphylococcus aureus and Panton-Valentine leukocidin-producing strains of Staph. aureus are being increasingly reported.A multidisciplinary integrated evidence-based approach is required to optimise outcomes.Further large-scale, multicentre studies are needed to delineate the optimal management of paediatric osteoarticular infection. Cite this article: EFORT Open Rev 2017;1:7-12. DOI: 10.1302/2058-5241.2.160027.

Primary follicular lymphoma of the testis and epididymis in adults.

Abstract: Primary testicular lymphomas typically occur in patients over 60 years of age. Most are diffuse large B-cell lymphomas with frequent dissemination and a poor prognosis. Primary follicular lymphoma of the adult testis has not been well characterized. However, a small number of primary testicular follicular lymphomas have recently been described in children. These showed stage 1E disease, a lack of BCL2 gene rearrangement and Bcl-2 protein expression, and a good clinical outcome. Here, we describe 5 cases of primary follicular lymphoma of the testis and epididymis in adults. These presented as unilateral testicular masses 12 to 40 mm in diameter and were characterized histologically by small neoplastic follicles in a sclerotic background. The neoplastic cells expressed CD10 and Bcl-6, but not Bcl-2 and lacked t(14;18)(q32;q21)/IGH-BCL2 and BCL6 gene rearrangements. Four of the five patients were 35 years old or younger, and 4 presented with stage 1EA disease. Although follow-up is 12 months or less in 2 of the 5 patients, to date each has followed an indolent clinical course. These features are different from those of most adult nodal follicular lymphomas but are very similar to those of the pediatric primary testicular follicular lymphomas. Together, the pediatric and adult cases represent a discrete clinicopathologic entity of t(14;18)(q32;q21)/IGH-BCL2-negative primary follicular lymphoma of the testis and epididymis, which typically present as clinically indolent localized disease in young males and should be distinguished from the diffuse large B-cell lymphoma more frequently seen in the testes of older adults.