Publications by authors named "Melanie Irvin-Sellers"

8 Publications

  • Page 1 of 1

SARS-CoV-2 antibody seroprevalence in NHS healthcare workers in a large double-sited UK hospital.

Clin Med (Lond) 2021 05 23;21(3):e290-e294. Epub 2021 Mar 23.

Institute of Cardiovascular Research, Royal Holloway University of London, and consultant neurologist, Imperial College Healthcare NHS Trust, London, UK

We determined the seroprevalence of SARS-CoV-2 antibodies in NHS healthcare workers (HCWs) in a cross-sectional study from a large general hospital located in a double-sited rural and semi-rural area. The sample size of 3,119 HCWs (mean age 43±13) consisted of 75.2% women, 61.1% White individuals and predominantly (62.4%) asymptomatic individuals. Seroprevalence of SARS-CoV-2 antibodies was 19.7%. Determinants of seropositivity were preceding symptomatic infection and non-White ethnicity. Regardless of staff role or sex, multivariate regression analysis revealed that non-White HCWs were three times (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.53-3.86, P<0.001) more likely to have antibodies than White staff, and seven times (OR 7.10, 95% CI 5.72-8.87, P<0.001) more likely if there was a history of preceding symptoms. We report relatively high rates of seropositivity in all NHS healthcare workers. Non-White symptomatic HCWs were significantly more likely to be seropositive than their colleagues, independent of age, sex or staff role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7861/clinmed.2020-1096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140688PMC
May 2021

Prestroke Disability Predicts Adverse Poststroke Outcome: A Registry-Based Prospective Cohort Study of Acute Stroke.

Stroke 2020 02 17;51(2):594-600. Epub 2019 Dec 17.

From the Institute of Cardiovascular Research, Royal Holloway University of London, Egham, United Kingdom (T.S.H., S.S., P.S.).

Background and Purpose- Information on what effect disability before stroke can have on stroke outcome is lacking. We assessed prestroke disability in relation to poststroke hospital outcome. Methods- Analysis of prospectively collected data from the Sentinel Stroke National Audit Programme. A total of 1656 men (mean age ±SD =73.1±13.2 years) and 1653 women (79.3±13.0 years) were admitted to hyperacute stroke units with acute stroke in 4 major UK between 2014 and 2016. Prestroke disability, assessed by modified Rankin Scale (mRS), was tested against poststroke adverse outcomes, adjusted for age, sex, and coexisting morbidities. Results- Compared with patients with prestroke mRS score =0, individuals with prestroke mRS scores =3, 4, or 5 had greater adjusted risks of moderately severe or severe stroke on arrival (4.4% versus 16.7%; odds ratio [OR], 3.2 [95% CI, 2.3-4.6] <0.001); urinary tract infection or pneumonia within 7 days of admission (9.6% versus 35.9%; OR, 3.7 [95% CI, 2.8-4.8] <0.001); mortality (7.2% versus 37.1%; OR, 4.9 [95% CI, 3.7-6.5] <0.001); requiring help with activities of daily living on discharge (12.3% versus 26.7%; OR, 3.1 [95% CI, 2.3-4.1] <0.001); and transferred to new care home (2.4% versus 9.4%; OR, 2.1 [95% CI, 1.3-3.3] =0.002). Patients with mRS scores =1 or 2 had intermediate risk of adverse outcomes. Overall, those with a mRS score =1 or 2 had length of stay on hyperacute stroke units extended by 5.3 days (95% CI, 2.8-7.7; <0.001) and mRS score =3, 4 or 5 by 7.2 days (95% CI, 4.0-10.5; <0.001). Conclusions- Individuals with evidence of prestroke disability, assessed by mRS, had significantly increased risk of poststroke adverse outcomes and longer length of stay on hyperacute stroke units and higher level of care on discharge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.027740DOI Listing
February 2020

Associations of 4AT with mobility, length of stay and mortality in hospital and discharge destination among patients admitted with hip fractures.

Age Ageing 2020 04;49(3):411-417

Institute of Cardiovascular Research, Royal Holloway, University of London, Surrey TW20 0EX, UK.

Background: the 4AT (Alertness, Abbreviated Mental Test-4, Attention and Acute change or fluctuating course), a tool to screen cognitive impairment and delirium, has recently been recommended by the Scottish Intercollegiate Guidelines Network. We examined its ability to predict health outcomes among patients admitted with hip fractures to a single hospital between January 2018 and June 2019.

Methods: the 4AT was performed within 1 day after hip surgery. A 4AT score of 0 means unlikely delirium or severe cognitive impairment (reference group); a score of 1-3 suggests possible chronic cognitive impairment, without excluding possibility of delirium; a score ≥ 4 suggests delirium with or without chronic cognitive impairment. Logistic regression, adjusted for: age; sex; nutritional status; co-morbidities; polypharmacy; and anticholinergic burden, used the 4AT to predict mobility, length of stay (LOS), mortality and discharge destination, compared with the reference group.

Results: from 537 (392 women, 145 men: mean = 83.7 ± standard deviation [SD] = 8.8 years) consecutive patients, 522 completed the 4AT; 132 (25%) had prolonged LOS (>2 weeks) and 36 (6.8%) died in hospital. Risk of failure to mobilise within 1 day of surgery was increased with a 4AT score ≥ 4 (OR = 2.4, 95% confidence interval [CI] = 1.3-4.3). Prolonged LOS was increased with 4AT scores of 1-3 (OR = 2.4, 95%CI = 1.4-4.1) or ≥4 (OR = 3.1, 95%CI = 1.9-6.7). In-patient mortality was increased with a 4AT score ≥ 4 (OR = 3.1, 95%CI = 1.2-8.2) but not with a 4AT score of 1-3. Change of residence on discharge was increased with a 4AT score ≥ 4 (OR = 3.1, 95%CI = 1.4-6.8). These associations persisted after excluding patients with dementia. 4AT score = 1-3 and ≥ 4 associated with increased LOS by 3 and 6 days, respectively.

Conclusions: for older adults with hip fracture, the 4AT independently predicts immobility, prolonged LOS, death in hospital and change in residence on discharge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ageing/afz161DOI Listing
April 2020

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

Nature 2017 04;545(7655):446-451

Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature22364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812436PMC
April 2017

Tracking the Evolution of Non-Small-Cell Lung Cancer.

N Engl J Med 2017 06 26;376(22):2109-2121. Epub 2017 Apr 26.

From the Cancer Research UK Lung Cancer Centre of Excellence (M.J.-H., G.A.W., N. McGranahan, N.J.B., S.V., S.S., D.H.J., R.R., S.-M.L., M.D.F., C.A., S.M.J., C.D., C.S.), London and Manchester, Good Clinical Laboratory Practice Facility, University College London (UCL) Experimental Cancer Medicine Centre (H.L.L., J.A.H.), Bill Lyons Informatics Centre (J.H.), and Cancer Immunology Unit (S.A.Q.), UCL Cancer Institute, the Translational Cancer Therapeutics Laboratory (G.A.W., N. McGranahan, N.J.B., T.B.K.W., A.R., T.C., S. Turajlic, H.X., C.T.H., C.S.), Department of Bioinformatics and Biostatistics (R.M., M.S., S.H., M.E., A.S.), Advanced Sequencing Facility (N. Matthews), and Cancer Genomics Laboratory (S.D., P.V.L.), Francis Crick Institute, the Renal and Skin Units, Royal Marsden Hospital (S. Turajlic), the Departments of Medical Oncology (M.J.-H., S.-M.L., M.D.F., T.A., C.A., C.S.), Pathology (M.F., E.B., T.M.), Cardiothoracic Surgery (D.L., M.H., S. Kolvekar, N.P.), Respiratory Medicine (S.M.J., R.T.), and Radiology (A.A.), UCL Hospitals, Lungs for Living, UCL Respiratory, UCL (S.M.J.), the Department of Radiotherapy, North Middlesex University Hospital (G.A.), the Department of Respiratory Medicine, Royal Free Hospital (S. Khan), and UCL Cancer Research UK and Cancer Trials Centre (N.I., H.B., Y.N., A.H.), London, Cancer Studies, University of Leicester (D.A.M., D.A.F., J.A.S., J.L.Q.), the Department of Thoracic Surgery, Glenfield Hospital (A.N., S.R.), and the Medical Research Center Toxicology Unit (J.L.Q.), Leicester, the Institute of Cancer Studies, University of Manchester (F.B.), the Christie Hospital (F.B., Y.S.), the Departments of Cardiothoracic Surgery (R.S.) and Pathology (L.J., A.M.Q.) and the North West Lung Centre (P.A.C.), University Hospital of South Manchester, and Cancer Research UK Manchester Institute (C.D.), Manchester, the Departments of Thoracic Surgery (B.N.) and Cellular Pathology (G.L., S. Trotter), Birmingham Heartlands Hospital, Molecular Pathology Diagnostic Services, Queen Elizabeth Hospital (P.T., B.O.), and Institute of Immunology and Immunotherapy, University of Birmingham (G.M.), Birmingham, the Departments of Medical Oncology (M.N.), Cardiothoracic Surgery (H.R.), Pathology (K.K.), Respiratory Medicine (M.C.), and Radiology (L.G.), Aberdeen University Medical School and Aberdeen Royal Infirmary, Aberdeen, the Department of Respiratory Medicine, Barnet and Chase Farm Hospitals, Barnet (S. Khan), the Department of Respiratory Medicine, Princess Alexandra Hospital, Harlow (P.R.), the Department of Clinical Oncology, St. Luke's Cancer Centre, Guildford (V.E.), the Departments of Pathology (B.I.), Respiratory Medicine (M.I.-S.), and Radiology (V.P.), Ashford and St. Peters' Hospitals, Surrey, the Department of Clinical Oncology, Velindre Hospital (J.F.L.), the Departments of Radiology (H.A.) and Respiratory Medicine (H.D.), University Hospital Llandough, the Departments of Pathology (R.A.) and Cardiothoracic Surgery (M.K.), University Hospital of Wales, and Cardiff University (R.A.), Cardiff, and Wellcome Trust Sanger Institute, Hinxton, and Big Data Institute, University of Oxford, Oxford (S.D.) - all in the United Kingdom; the Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby (Z.S.); the Computational Health Informatics Program, Boston Children's Hospital and Harvard Medical School, Boston (Z.S.); MTA-SE-NAP, Brain Metastasis Research Group, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary (Z.S.); Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine, Berlin (R.F.S.); and the Department of Human Genetics, University of Leuven, Leuven, Belgium (P.V.L.).

Background: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC.

Methods: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival.

Results: We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10), which remained significant in multivariate analysis.

Conclusions: Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1616288DOI Listing
June 2017

Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease.

Cochrane Database Syst Rev 2015 Sep 22(9):CD009552. Epub 2015 Sep 22.

Respiratory Medicine, Bradford Teaching Hospitals NHS Foundation Trust, Duckworth Lane, Bradford, UK.

Background: Tiotropium and ipratropium bromide are both recognised treatments in the management of people with stable chronic obstructive pulmonary disease (COPD). There are new studies which have compared tiotropium with ipratropium bromide, making an update necessary.

Objectives: To compare the relative effects of tiotropium to ipratropium bromide on markers of quality of life, exacerbations, symptoms, lung function and serious adverse events in patients with COPD using available randomised controlled trial (RCT) data.

Search Methods: We identified RCTs from the Cochrane Airways Group Specialised Register of trials (CAGR) and ClinicalTrials.gov up to August 2015.

Selection Criteria: We included parallel group RCTs of 12 weeks duration or longer comparing treatment with tiotropium with ipratropium bromide for patients with stable COPD.

Data Collection And Analysis: Two review authors independently assessed studies for inclusion and then extracted data on study quality and outcome results. We contacted trial sponsors for additional information. We analysed the data using Cochrane Review Manager.

Main Results: This review included two studies of good methodological quality that enrolled 1073 participants with COPD. The studies used a similar design and inclusion criteria and were of at least 12 weeks duration; the participants had a mean forced expiratory volume in one second (FEV1) of 40% predicted value at baseline. One study used tiotropium via the HandiHaler (18 µg) for 12 months and the other via the Respimat device (5 µg and 10 µg) for 12 weeks. In general, the treatment groups were well matched at baseline but not all outcomes were reported for both studies. Overall the risk of bias across the included RCTs was low.For primary outcomes this review found that at the three months trough (the lowest level measured before treatment) FEV1 significantly increased with tiotropium compared to ipratropium bromide (mean difference (MD) 109 mL; 95% confidence interval (CI) 81 to 137, moderate quality evidence, I(2) = 62%). There were fewer people experiencing one or more non-fatal serious adverse events on tiotropium compared to ipratropium (odds ratio (OR) 0.5; 95% CI 0.34 to 0.73, high quality evidence). This represents an absolute reduction in risk from 176 to 97 per 1000 people over three to 12 months. Concerning disease specific adverse events, the tiotropium group were also less likely to experience a COPD-related serious adverse event when compared to ipratropium bromide (OR 0.59; 95% CI 0.41 to 0.85, moderate quality evidence).For secondary outcomes, both studies reported fewer hospital admissions in the tiotropium group (OR 0.34; 95% CI 0.15 to 0.70, moderate quality evidence); as well as fewer patients experiencing one or more exacerbations leading to hospitalisation in the people on tiotropium in both studies (OR 0.56; 95% CI 0.31 to 0.99, moderate quality evidence). There was no significant difference in mortality between the treatments (OR 1.39; 95% CI 0.44 to 4.39, moderate quality evidence). One study measured quality of life using the St George's Respiratory Questionnaire (SGRQ); the mean SGRQ score at 52 weeks was lower in the tiotropium group than the ipratropium group (lower on the scale is favourable) (MD -3.30; 95% CI -5.63 to -0.97, moderate quality evidence). There were fewer participants suffering one of more exacerbations in the tiotropium arm (OR 0.71; 95% CI 0.52 to 0.95, high quality evidence) and there was also a reported difference in the mean number of exacerbations per person per year which reached statistical significance (MD -0.23; 95% CI -0.39 to -0.07, P = 0.006, moderate quality evidence). From the 1073 participants there were significantly fewer withdrawals from the tiotropium group (OR 0.58; 95% CI 0.41 to 0.83, high quality evidence).

Authors' Conclusions: This review shows that tiotropium treatment, when compared with ipratropium bromide, was associated with improved lung function, fewer hospital admissions (including those for exacerbations of COPD), fewer exacerbations of COPD and improved quality of life. There were both fewer serious adverse events and disease specific events in the tiotropium group, but no significant difference in deaths with ipratropium bromide when compared to tiotropium. Thus, tiotropium appears to be a reasonable choice (instead of ipratropium bromide) for patients with stable COPD, as proposed in guidelines. A recent large double-blind trial of the two delivery devices found no substantial difference in mortality using 2.5 µg or 5 µg of tiotropium via Respimat in comparison to 18 µg via Handihaler.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD009552.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749963PMC
September 2015

Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease.

Cochrane Database Syst Rev 2013 Sep 16(9):CD009552. Epub 2013 Sep 16.

Respiratory Medicine, Bradford Teaching Hospitals NHS Foundation Trust, Duckworth Lane, Bradford, UK.

Background: Tiotropium and ipratropium bromide are both recognised treatments in the management of people with stable chronic obstructive pulmonary disease (COPD). There are new studies which have compared tiotropium with ipratropium bromide, making an update necessary.

Objectives: To compare the relative effects of tiotropium to ipratropium bromide on markers of quality of life, exacerbations, symptoms, lung function and serious adverse events in patients with COPD using available randomised controlled trial (RCT) data.

Search Methods: We identified RCTs from the Cochrane Airways Group Specialised Register of trials (CAGR) and ClinicalTrials.gov up to November 2012.

Selection Criteria: We included parallel group RCTs of 12 weeks duration or longer comparing treatment with tiotropium with ipratropium bromide for patients with stable COPD.

Data Collection And Analysis: Two review authors independently assessed studies for inclusion and then extracted data on study quality and outcome results. We contacted trial sponsors for additional information. We analysed the data using Cochrane Review Manager (RevMan 5.2).

Main Results: This review included two studies of good methodological quality that enrolled 1073 participants with COPD. The studies used a similar design and inclusion criteria and were of at least 12 weeks duration; the participants had a mean forced expiratory volume in one second (FEV1) of 40% predicted value at baseline. One study used tiotropium via the HandiHaler (18 µg) for 12 months and the other via the Respimat device (5 µg and 10 µg) for 12 weeks. In general, the treatment groups were well matched at baseline but not all outcomes were reported for both studies. Overall the risk of bias across the included RCTs was low.For primary outcomes this review found that at the three months trough (the lowest level measured before treatment) FEV1 significantly increased with tiotropium compared to ipratropium bromide (mean difference (MD) 109 mL; 95% confidence interval (CI) 81 to 137, moderate quality evidence, I(2) = 62%). There were fewer people experiencing one or more non-fatal serious adverse events on tiotropium compared to ipratropium (odds ratio (OR) 0.5; 95% CI 0.34 to 0.73, high quality evidence). This represents an absolute reduction in risk from 176 to 97 per 1000 people over three to 12 months. Concerning disease specific adverse events, the tiotropium group were also less likely to experience a COPD-related serious adverse event when compared to ipratropium bromide (OR 0.59; 95% CI 0.41 to 0.85, moderate quality evidence).For secondary outcomes, both studies reported fewer hospital admissions in the tiotropium group (OR 0.34; 95% CI 0.15 to 0.70, moderate quality evidence); as well as fewer patients experiencing one or more exacerbations leading to hospitalisation in the people on tiotropium in both studies (OR 0.56; 95% CI 0.31 to 0.99, moderate quality evidence). There was no significant difference in mortality between the treatments (OR 1.39; 95% CI 0.44 to 4.39, moderate quality evidence). One study measured quality of life using the St George's Respiratory Questionnaire (SGRQ); the mean SGRQ score at 52 weeks was lower in the tiotropium group than the ipratropium group (lower on the scale is favourable) (MD -3.30; 95% CI -5.63 to -0.97, moderate quality evidence). There were fewer participants suffering one of more exacerbations in the tiotropium arm (OR 0.71; 95% CI 0.52 to 0.95, high quality evidence) and there was also a reported difference in the mean number of exacerbations per person per year which reached statistical significance (MD -0.23; 95% CI -0.39 to -0.07, P = 0.006, moderate quality evidence). From the 1073 participants there were significantly fewer withdrawals from the tiotropium group (OR 0.58; 95% CI 0.41 to 0.83, high quality evidence).

Authors' Conclusions: This review shows that tiotropium treatment, when compared with ipratropium bromide, was associated with improved lung function, fewer hospital admissions (including those for exacerbations of COPD), fewer exacerbations of COPD and improved quality of life. There were both fewer serious adverse events and disease specific events in the tiotropium group, but no significant difference in deaths with ipratropium bromide when compared to tiotropium. Thus, tiotropium appears to be a reasonable choice (instead of ipratropium bromide) for patients with stable COPD, as proposed in guidelines. We would advise some caution with tiotropium via the Respimat inhaler and suggest waiting for further information from an ongoing head-to-head trial comparing mortality in relation to tiotropium delivery devices and doses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD009552.pub2DOI Listing
September 2013
-->