Author: "Jenna Morgan" - Searchworks@Jio Institute Digital Library Search Results

139 results on '"Jenna Morgan"'

1. Management and outcomes for older women with early breast cancer treated with primary endocrine therapy (PET)

Author: Thomas Hubbard, Georgia Wright, Jenna Morgan, Charlene Martin, Stephen Walters, Kwok-Leung Cheung, Riccardo Audisio, Malcolm Reed, and Lynda Wyld
Subjects: Breast neoplasms, Endocrine therapy, Older adult, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: This study reports the detailed management and outcomes of women treated with Primary Endocrine Therapy (PET) in a large prospective UK cohort of older women (≥70) with breast cancer. Methods: This was an unplanned secondary analysis of a prospective, multicentre, observational study (The Age Gap study). Data were collected at baseline and regular intervals on patient, tumour and treatment characteristics with tumour RECIST response category recorded. Direct study follow-up was 24 months with longer-term survival data obtained from the UK cancer registry. Results: The Age Gap study recruited 3316 women across 56 breast units. Primary endocrine therapy (PET) was initiated for 505/3316 (15 %) women; median age was 84 (IQR 79–88) with median follow-up 41.9 months (IQR 27–60). Death occurred in 205/505(40.6 %) patients, 160/205; 78 % non- Breast Cancer related, 45/205; 21.9 % Breast Cancer related. Multivariate analysis identified older age (HR-1.055(95 % Confidence Interval: 1.029–1.084); P 0.05). Conclusion: Early disease response and change of endocrine therapy are not significantly associated with overall survival, conversion to surgery is linked to improved outcome. Prognosis is largely determined by age and comorbidity in older women treated with PET.
Published: 2024
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2. Process evaluation of the Bridging the Age Gap in Breast Cancer decision support intervention cluster randomised trial

Author: Maria Burton, Kate J. Lifford, Lynda Wyld, Fiona Armitage, Alistair Ring, Anthony Nettleship, Karen Collins, Jenna Morgan, Malcolm W. R. Reed, Geoffrey R. Holmes, Mike Bradburn, Jacqui Gath, Tracy Green, Deirdre Revell, Kate Brain, Adrian Edwards, and On behalf of the Study Management Team
Subjects: Breast cancer, Older women, Decision support, Shared decision-making, Intervention implementation, Process evaluation, Medicine (General), R5-920
Abstract: Abstract Background The Bridging the Age Gap in Breast Cancer research programme sought to improve treatment decision-making for older women with breast cancer by developing and testing, in a cluster randomised trial (n = 1339 patients), two decision support interventions (DESIs). Both DESIs were used in the intervention arm and each comprised an online risk prediction model, brief decision aid and information booklet. One DESI supported the decision to have either primary endocrine therapy (PET) or surgery with adjuvant therapies and the second supported the decision to have adjuvant chemotherapy after surgery or not. Methods Sixteen sites were randomly selected to take part in the process evaluation. Multiple methods of data collection were used. Medical Research Council (MRC) guidelines for the evaluation of complex interventions were used. Results Eighty-two patients, mean age 75.5 (range 70–93), provided data for the process evaluation. Seventy-three interviews were completed with patients. Ten clinicians from six intervention sites took part in telephone interviews. Dose: Ninety-one members of staff in the intervention arm received intervention training. Reach: The online tool was accessed on 324 occasions by 27 clinicians. Reasons for non-use of the online tool were commonly that the patient had already made a decision or that there was no online access in the clinic. Of the 32 women for whom there were data available, fifteen from the intervention arm and six from the usual care arm were offered a choice of treatment. Fidelity: Clinicians used the online tool in different ways, with some using it during the consultation and others checking the online survival estimates before the consultation. Adaptation: There was evidence of adaptation when using the DESIs. A lack of infrastructure, e.g. internet access, was a barrier to the use of the online tool. The brief decision aid was rarely used. Mediators: Shared decision-making: Most patients felt able to contribute to decision-making and expressed high levels of satisfaction with the process. Participants’ responses to intervention: Six patients reported the DESIs to be very useful, one somewhat useful and two moderately useful. Conclusions Clinicians who participated were mainly supportive of the interventions and had attempted some adaptations to make the interventions applicable, but there were practical and engagement barriers that led to sub-optimal adoption in routine practice. Trial registration ISRCTN46099296 . Registered on 11 August 2016—retrospectively registered
Published: 2021
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3. Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

Author: Lynda Wyld, Malcolm WR Reed, Karen Collins, Sue Ward, Geoff Holmes, Jenna Morgan, Mike Bradburn, Stephen Walters, Maria Burton, Kate Lifford, Adrian Edwards, Kate Brain, Alistair Ring, Esther Herbert, Thompson G Robinson, Charlene Martin, Tim Chater, Kirsty Pemberton, Anne Shrestha, Anthony Nettleship, Paul Richards, Alan Brennan, Kwok Leung Cheung, Annaliza Todd, Helena Harder, Riccardo Audisio, Nicolo Matteo Luca Battisti, Juliet Wright, Richard Simcock, Christopher Murray, Alastair M Thompson, Margot Gosney, Matthew Hatton, Fiona Armitage, Julietta Patnick, Tracy Green, Deirdre Revill, Jacqui Gath, Kieran Horgan, Chris Holcombe, Matt Winter, Jay Naik, and Rishi Parmeshwar
Subjects: breast cancer, older women, surgery, primary endocrine therapy, chemotherapy, survival, quality of life, shared decision-making, decision support tool, cluster randomised trial, cohort study, Public aspects of medicine, RA1-1270
Abstract: Background: In breast cancer management, age-related practice variation is widespread, with older women having lower rates of surgery and chemotherapy than younger women, based on the premise of reduced treatment tolerance and benefit. This may contribute to inferior outcomes. There are currently no age- and fitness-stratified guidelines on which to base treatment recommendations. Aim: We aimed to optimise treatment choice and outcomes for older women (aged ≥ 70 years) with operable breast cancer. Objectives: Our objectives were to (1) determine the age, comorbidity, frailty, disease stage and biology thresholds for endocrine therapy alone versus surgery plus adjuvant endocrine therapy, or adjuvant chemotherapy versus no chemotherapy, for older women with breast cancer; (2) optimise survival outcomes for older women by improving the quality of treatment decision-making; (3) develop and evaluate a decision support intervention to enhance shared decision-making; and (4) determine the degree and causes of treatment variation between UK breast units. Design: A prospective cohort study was used to determine age and fitness thresholds for treatment allocation. Mixed-methods research was used to determine the information needs of older women to develop a decision support intervention. A cluster-randomised trial was used to evaluate the impact of this decision support intervention on treatment choices and outcomes. Health economic analysis was used to evaluate the cost–benefit ratio of different treatment strategies according to age and fitness criteria. A mixed-methods study was used to determine the degree and causes of variation in treatment allocation. Main outcome measures: The main outcome measures were enhanced age- and fitness-specific decision support leading to improved quality-of-life outcomes in older women (aged ≥ 70 years) with early breast cancer. Results: (1) Cohort study: the study recruited 3416 UK women aged ≥ 70 years (median age 77 years). Follow-up was 52 months. (a) The surgery plus adjuvant endocrine therapy versus endocrine therapy alone comparison: 2854 out of 3416 (88%) women had oestrogen-receptor-positive breast cancer, 2354 of whom received surgery plus adjuvant endocrine therapy and 500 received endocrine therapy alone. Patients treated with endocrine therapy alone were older and frailer than patients treated with surgery plus adjuvant endocrine therapy. Unmatched overall survival and breast-cancer-specific survival were higher in the surgery plus adjuvant endocrine therapy group (overall survival: hazard ratio 0.27, 95% confidence interval 0.23 to 0.33; p 25]. In this high-risk population, there were no differences according to adjuvant chemotherapy use in overall survival or breast-cancer-specific survival after propensity matching. Adjuvant chemotherapy was associated with a lower risk of metastatic recurrence than no chemotherapy in the unmatched (adjusted hazard ratio 0.36, 95% confidence interval 0.19 to 0.68; p = 0.002) and propensity-matched patients (adjusted hazard ratio 0.43, 95% confidence interval 0.20 to 0.92; p = 0.03). Adjuvant chemotherapy improved the overall survival and breast-cancer-specific survival of patients with oestrogen-receptor-negative disease. (2) Mixed-methods research to develop a decision support intervention: an iterative process was used to develop two decision support interventions (each comprising a brief decision aid, a booklet and an online tool) specifically for older women facing treatment choices (endocrine therapy alone or surgery plus adjuvant endocrine therapy, and adjuvant chemotherapy or no chemotherapy) using several evidence sources (expert opinion, literature and patient interviews). The online tool was based on models developed using registry data from 23,842 patients and validated on an external data set of 14,526 patients. Mortality rates at 2 and 5 years differed by 90 years, surgery plus adjuvant endocrine therapy was no longer cost-effective and generated fewer quality-adjusted life-years than endocrine therapy alone. The incremental benefit of surgery plus adjuvant endocrine therapy reduced with age and comorbidities. (5) Variation in practice: analysis of rates of surgery plus adjuvant endocrine therapy or endocrine therapy alone between the 56 breast units in the cohort study demonstrated significant variation in rates of endocrine therapy alone that persisted after adjustment for age, fitness and stage. Clinician preference was an important determinant of treatment choice. Conclusions: This study demonstrates that, for older women with oestrogen-receptor-positive breast cancer, there is a cohort of women with a life expectancy of
Published: 2022
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4. Phylogeny of bacterial and archaeal genomes using conserved genes: supertrees and supermatrices.

Author: Jenna Morgan Lang, Aaron E Darling, and Jonathan A Eisen
Subjects: Medicine, Science
Abstract: Over 3000 microbial (bacterial and archaeal) genomes have been made publically available to date, providing an unprecedented opportunity to examine evolutionary genomic trends and offering valuable reference data for a variety of other studies such as metagenomics. The utility of these genome sequences is greatly enhanced when we have an understanding of how they are phylogenetically related to each other. Therefore, we here describe our efforts to reconstruct the phylogeny of all available bacterial and archaeal genomes. We identified 24, single-copy, ubiquitous genes suitable for this phylogenetic analysis. We used two approaches to combine the data for the 24 genes. First, we concatenated alignments of all genes into a single alignment from which a Maximum Likelihood (ML) tree was inferred using RAxML. Second, we used a relatively new approach to combining gene data, Bayesian Concordance Analysis (BCA), as implemented in the BUCKy software, in which the results of 24 single-gene phylogenetic analyses are used to generate a "primary concordance" tree. A comparison of the concatenated ML tree and the primary concordance (BUCKy) tree reveals that the two approaches give similar results, relative to a phylogenetic tree inferred from the 16S rRNA gene. After comparing the results and the methods used, we conclude that the current best approach for generating a single phylogenetic tree, suitable for use as a reference phylogeny for comparative analyses, is to perform a maximum likelihood analysis of a concatenated alignment of conserved, single-copy genes.
Published: 2013
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5. Bacterial communities of diverse Drosophila species: ecological context of a host-microbe model system.

Author: James Angus Chandler, Jenna Morgan Lang, Srijak Bhatnagar, Jonathan A Eisen, and Artyom Kopp
Subjects: Genetics, QH426-470
Abstract: Drosophila melanogaster is emerging as an important model of non-pathogenic host-microbe interactions. The genetic and experimental tractability of Drosophila has led to significant gains in our understanding of animal-microbial symbiosis. However, the full implications of these results cannot be appreciated without the knowledge of the microbial communities associated with natural Drosophila populations. In particular, it is not clear whether laboratory cultures can serve as an accurate model of host-microbe interactions that occur in the wild, or those that have occurred over evolutionary time. To fill this gap, we characterized natural bacterial communities associated with 14 species of Drosophila and related genera collected from distant geographic locations. To represent the ecological diversity of Drosophilids, examined species included fruit-, flower-, mushroom-, and cactus-feeders. In parallel, wild host populations were compared to laboratory strains, and controlled experiments were performed to assess the importance of host species and diet in shaping bacterial microbiome composition. We find that Drosophilid flies have taxonomically restricted bacterial communities, with 85% of the natural bacterial microbiome composed of only four bacterial families. The dominant bacterial taxa are widespread and found in many different host species despite the taxonomic, ecological, and geographic diversity of their hosts. Both natural surveys and laboratory experiments indicate that host diet plays a major role in shaping the Drosophila bacterial microbiome. Despite this, the internal bacterial microbiome represents only a highly reduced subset of the external bacterial communities, suggesting that the host exercises some level of control over the bacteria that inhabit its digestive tract. Finally, we show that laboratory strains provide only a limited model of natural host-microbe interactions. Bacterial taxa used in experimental studies are rare or absent in wild Drosophila populations, while the most abundant associates of natural Drosophila populations are rare in the lab.
Published: 2011
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6. The genome of the intracellular bacterium of the coastal bivalve, Solemya velum: a blueprint for thriving in and out of symbiosis

Author: Dmytrenko, Oleg, Russell, Shelbi L, Loo, Wesley T, Fontanez, Kristina M, Liao, Li, Roeselers, Guus, Sharma, Raghav, Stewart, Frank J, Newton, Irene LG, Woyke, Tanja, Wu, Dongying, Lang, Jenna Morgan, Eisen, Jonathan A, and Cavanaugh, Colleen M
Subjects: Microbiology, Biological Sciences, Ecology, Genetics, Human Genome, Life Below Water, Animals, Base Composition, Bivalvia, DNA Transposable Elements, Ecosystem, Genes, Bacterial, Genome, Bacterial, Intracellular Space, Metabolic Networks and Pathways, Molecular Sequence Data, Oxidation-Reduction, RNA, Transfer, Symbiosis, Chemosynthesis, Sulfur oxidation, Respiratory flexibility, H+/Na+ -membrane cycles, Calvin cycle, Pyrophosphate-dependent phosphofructokinase, Heterotrophy, Motility, Mobile genetic elements, Information and Computing Sciences, Medical and Health Sciences, Bioinformatics, Biological sciences, Biomedical and clinical sciences
Abstract: BackgroundSymbioses between chemoautotrophic bacteria and marine invertebrates are rare examples of living systems that are virtually independent of photosynthetic primary production. These associations have evolved multiple times in marine habitats, such as deep-sea hydrothermal vents and reducing sediments, characterized by steep gradients of oxygen and reduced chemicals. Due to difficulties associated with maintaining these symbioses in the laboratory and culturing the symbiotic bacteria, studies of chemosynthetic symbioses rely heavily on culture independent methods. The symbiosis between the coastal bivalve, Solemya velum, and its intracellular symbiont is a model for chemosynthetic symbioses given its accessibility in intertidal environments and the ability to maintain it under laboratory conditions. To better understand this symbiosis, the genome of the S. velum endosymbiont was sequenced.ResultsRelative to the genomes of obligate symbiotic bacteria, which commonly undergo erosion and reduction, the S. velum symbiont genome was large (2.7 Mb), GC-rich (51%), and contained a large number (78) of mobile genetic elements. Comparative genomics identified sets of genes specific to the chemosynthetic lifestyle and necessary to sustain the symbiosis. In addition, a number of inferred metabolic pathways and cellular processes, including heterotrophy, branched electron transport, and motility, suggested that besides the ability to function as an endosymbiont, the bacterium may have the capacity to live outside the host.ConclusionsThe physiological dexterity indicated by the genome substantially improves our understanding of the genetic and metabolic capabilities of the S. velum symbiont and the breadth of niches the partners may inhabit during their lifecycle.
Published: 2014

7. Draft Genome Sequence of Leucobacter sp. Strain UCD-THU (Phylum Actinobacteria)

Author: Holland-Moritz, Hannah, Bevans, Dakota, Lang, Jenna Morgan, Darling, Aaron, Eisen, Jonathan Andrew, and Coil, David
Subjects: genomes, microbiology, built environment
Abstract: Here we present the draft genome of Leucobacter sp. strain UCD-THU. The genome contains 3,317,267 bp in 11 scaffolds. This strain was isolated from a residential toilet as part of an undergraduate project to sequence reference genomes of microbes from the built environment.
Published: 2013

8. Phylogeny of bacterial and archaeal genomes using conserved genes: supertrees and supermatrices.

Author: Lang, Jenna Morgan, Darling, Aaron E, and Eisen, Jonathan A
Subjects: Bacteria, Archaea, Genetic Markers, Likelihood Functions, Bayes Theorem, Evolution, Molecular, Phylogeny, Conserved Sequence, Genes, Archaeal, Genes, Bacterial, Evolution, Molecular, Genes, Archaeal, Bacterial, General Science & Technology
Abstract: Over 3000 microbial (bacterial and archaeal) genomes have been made publically available to date, providing an unprecedented opportunity to examine evolutionary genomic trends and offering valuable reference data for a variety of other studies such as metagenomics. The utility of these genome sequences is greatly enhanced when we have an understanding of how they are phylogenetically related to each other. Therefore, we here describe our efforts to reconstruct the phylogeny of all available bacterial and archaeal genomes. We identified 24, single-copy, ubiquitous genes suitable for this phylogenetic analysis. We used two approaches to combine the data for the 24 genes. First, we concatenated alignments of all genes into a single alignment from which a Maximum Likelihood (ML) tree was inferred using RAxML. Second, we used a relatively new approach to combining gene data, Bayesian Concordance Analysis (BCA), as implemented in the BUCKy software, in which the results of 24 single-gene phylogenetic analyses are used to generate a "primary concordance" tree. A comparison of the concatenated ML tree and the primary concordance (BUCKy) tree reveals that the two approaches give similar results, relative to a phylogenetic tree inferred from the 16S rRNA gene. After comparing the results and the methods used, we conclude that the current best approach for generating a single phylogenetic tree, suitable for use as a reference phylogeny for comparative analyses, is to perform a maximum likelihood analysis of a concatenated alignment of conserved, single-copy genes.
Published: 2013

9. Abstract OT3-20-02: SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial

Author: Stuart A. McIntosh, Charlotte E. Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Jenna Morgan, Sangeetha Paramasivan, Sarah E. Pinder, Sarah Pirrie, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, and Daniel Rea
Subjects: Cancer Research, Oncology
Abstract: Background: Mammographic screening programmes reduce breast cancer mortality, but detect many small tumours with favourable biological features which may not progress during a woman’s lifetime. Screen-detected cancers are treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies have evaluated the omission of radiotherapy in this context. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Methods: SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected good prognosis cancers. The main eligibility criteria are age ≥47 years, unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery; with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Non-inferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 7st July 2022, 142 patients had been randomised from 26 centres, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month, approaching the feasibility recruitment target of 144 patients. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced, with wider feedback delivered across sites via recruitment training workshops. Conclusion: Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme, award 17/42/32 Citation Format: Stuart A. McIntosh, Charlotte E. Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Jenna Morgan, Sangeetha Paramasivan, Sarah E. Pinder, Sarah Pirrie, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea. SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-02.
Published: 2023
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10. Bacterial communities of diverse Drosophila species: ecological context of a host-microbe model system.

Author: Chandler, James Angus, Lang, Jenna Morgan, Bhatnagar, Srijak, Eisen, Jonathan A, and Kopp, Artyom
Subjects: Animals, Drosophila, Bacteria, RNA, Ribosomal, 16S, Diet, Biodiversity, Symbiosis, Models, Biological, Population, Metagenome, Biological Evolution, Models, Biological, RNA, Ribosomal, 16S, Genetics, Developmental Biology
Abstract: Drosophila melanogaster is emerging as an important model of non-pathogenic host-microbe interactions. The genetic and experimental tractability of Drosophila has led to significant gains in our understanding of animal-microbial symbiosis. However, the full implications of these results cannot be appreciated without the knowledge of the microbial communities associated with natural Drosophila populations. In particular, it is not clear whether laboratory cultures can serve as an accurate model of host-microbe interactions that occur in the wild, or those that have occurred over evolutionary time. To fill this gap, we characterized natural bacterial communities associated with 14 species of Drosophila and related genera collected from distant geographic locations. To represent the ecological diversity of Drosophilids, examined species included fruit-, flower-, mushroom-, and cactus-feeders. In parallel, wild host populations were compared to laboratory strains, and controlled experiments were performed to assess the importance of host species and diet in shaping bacterial microbiome composition. We find that Drosophilid flies have taxonomically restricted bacterial communities, with 85% of the natural bacterial microbiome composed of only four bacterial families. The dominant bacterial taxa are widespread and found in many different host species despite the taxonomic, ecological, and geographic diversity of their hosts. Both natural surveys and laboratory experiments indicate that host diet plays a major role in shaping the Drosophila bacterial microbiome. Despite this, the internal bacterial microbiome represents only a highly reduced subset of the external bacterial communities, suggesting that the host exercises some level of control over the bacteria that inhabit its digestive tract. Finally, we show that laboratory strains provide only a limited model of natural host-microbe interactions. Bacterial taxa used in experimental studies are rare or absent in wild Drosophila populations, while the most abundant associates of natural Drosophila populations are rare in the lab.
Published: 2011

11. Abstract OT1-06-02: SMALL - Open surgery versus minimally invasive vacuum-assisted excision for small screen detected breast cancer: A phase 3 randomised trial

Author: Stuart A McIntosh, Charlotte E Coles, Carmel Conefrey, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Jenna Morgan, Sangeetha Paramasivan, Sarah Pinder, Sarah Pirrie, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, and Daniel Rea
Subjects: Cancer Research, Oncology
Abstract: Background:. Mammographic screening programmes have been shown to reduce breast cancer mortality. However, they detect many small tumours with favourable biological features which may not progress during a woman’s lifetime. These are treated with standard surgery and adjuvant therapies, which have associated morbidities. Thus, there is a need to reduce overtreatment of good prognosis tumours found by screening. Minimally invasive treatment approaches have been described but there is no prospective randomised evidence to support their routine use. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Methods:. SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected good prognosis breast cancers. The main eligibility criteria are age ≥47 years, screen-detected unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery; with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are:1.Non-inferiority comparison of the requirement for a second procedure following excision2.Single arm analysis of local recurrence (LR) at 5 years following VAE. Recruitment of 800 patients over 4 years will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A QuinteT Recruitment Intervention (QRI) is integrated throughout SMALL to optimise recruitment and informed consent. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of screening, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results:. SMALL opened in December 2019, but recruitment halted in 2020 due to suspension of the NHS BSP for 5 months due to COVID-19. As of 1st July 2021, 55 patients had been approached in 10 centres, with 33 patients randomised (randomisation rate 60%). A further 23 centres are in set-up, with 8 suspended due to the pandemic. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on introducing and discussing SMALL, providing balanced information. on treatment options and explaining randomisation). individual recruiter feedback has commenced, with wider feedback planned shortly. Conclusion:. Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme, award 17/42/32 Citation Format: Stuart A McIntosh, Charlotte E Coles, Carmel Conefrey, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Jenna Morgan, Sangeetha Paramasivan, Sarah Pinder, Sarah Pirrie, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea. SMALL - Open surgery versus minimally invasive vacuum-assisted excision for small screen detected breast cancer: A phase 3 randomised trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-06-02.
Published: 2022
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12. Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer

Author: Kate Lifford, Deirdre Revill, Annaliza Todd, Stephen J Walters, Katherine Emma Brain, Geoffrey Holmes, Lynda Wyld, Malcolm W.R. Reed, Jacqui Gath, Tracy Green, Tim Chater, Alan Brennan, Mike Bradburn, Jenna Morgan, Margot Gosney, Paul Richards, Matthew Hatton, Kwok-Leung Cheung, Adrian Edwards, Alistair Ring, Charlene Martin, Maria Burton, Rachid Rafia, J.T. Wright, Richard Simcock, Riccardo A. Audisio, Alistair Thomson, Sue Ward, Kirsty Pemberton, and Thompson G. Robinson
Subjects: Comparative Effectiveness Research, medicine.medical_specialty, Time Factors, Antineoplastic Agents, Hormonal, Cost effectiveness, Cost-Benefit Analysis, Health Status, medicine.medical_treatment, Clinical Decision-Making, Breast Neoplasms, Comorbidity, Risk Assessment, Drug Costs, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Quality of life, Risk Factors, Humans, Medicine, 030212 general & internal medicine, Prospective cohort study, Lymph node, Mastectomy, Aged, Early breast cancer, Models, Statistical, business.industry, 030503 health policy & services, Health Policy, Age Factors, Public Health, Environmental and Occupational Health, Endocrine therapy, medicine.disease, United Kingdom, Surgery, Models, Economic, Treatment Outcome, medicine.anatomical_structure, Chemotherapy, Adjuvant, Physical Fitness, Quality of Life, Female, 0305 other medical science, business, Adjuvant
Abstract: Objectives\ud \ud Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective.\ud \ud \ud Methods\ud \ud Survival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}.\ud \ud \ud Results\ud \ud For a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3).\ud \ud \ud Conclusion\ud \ud From a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life.
Published: 2021
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13. Breast ONCA: Breast surgery training opportunities national collaborative audit

Author: Alex Humphreys, Alona Courtney, Jenna Morgan, Louise Merker, Natasha Jiwa, and Rajiv Dave
Subjects: Oncology, Surgery, General Medicine
Published: 2023
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14. Bridging the age gap in breast cancer: impact of omission of breast cancer surgery in older women with oestrogen receptor-positive early breast cancer on quality-of-life outcomes

Author: Margot Gosney, Alistair Ring, R. Parmeschwar, Kate Lifford, Deirdre Revill, Lynda Wyld, Jacqui Gath, Jenna Morgan, Annaliza Todd, Geoffrey Holmes, Charlene Martin, Sue Ward, A.M. Thomson, Tim Chater, Anne Shrestha, Malcolm W.R. Reed, Adrian Edwards, Mike Bradburn, Matthew Hatton, Alan Brennan, Kirsty Pemberton, Jay Naik, Christopher Holcombe, Kwok-Leung Cheung, Thompson G. Robinson, J.T. Wright, T. Green, Stephen J Walters, Matthew C Winter, Maria Burton, Karen Collins, Esther Herbert, Riccardo A. Audisio, Richard Simcock, and Kieran Horgan
Subjects: medicine.medical_specialty, Antineoplastic Agents, Hormonal, medicine.medical_treatment, Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Quality of life, medicine, Humans, Longitudinal Studies, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Adverse effect, Mastectomy, Aged, Aged, 80 and over, business.industry, Cancer, medicine.disease, humanities, Surgery, Receptors, Estrogen, 030220 oncology & carcinogenesis, Propensity score matching, Quality of Life, Female, business, Cohort study
Abstract: Background Primary endocrine therapy may be an alternative treatment for less fit women with oestrogen receptor (ER)-positive breast cancer. This study compared quality-of-life (QoL) outcomes in older women treated with surgery or primary endocrine therapy. Methods This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer. QoL was assessed using European Organisation for Research and Treatment of cancer QoL questionnaires QLQ-C30, -BR23, and -ELD14, and the EuroQol Five Dimensions 5L score at baseline, 6 weeks, and 6, 12, 18, and 24 months. Propensity score matching was used to adjust for baseline variation in health, fitness, and tumour stage. Results The study recruited 3416 women (median age 77 (range 69–102) years) from 56 breast units. Of these, 2979 (87.2 per cent) had ER-positive breast cancer; 2354 women had surgery and 500 received primary endocrine therapy (125 were excluded from analysis due to inadequate data or non-standard therapy). Median follow-up was 52 months. The primary endocrine therapy group was older and less fit. Baseline QoL differed between the groups; the mean(s.d.) QLQ-C30 global health status score was 66.2(21.1) in patients who received primary endocrine therapy versus 77.1(17.8) among those who had surgery plus endocrine therapy. In the unmatched analysis, changes in QoL between 6 weeks and baseline were noted in several domains, but by 24 months most scores had returned to baseline levels. In the matched analysis, major surgery (mastectomy or axillary clearance) had a more pronounced adverse impact than primary endocrine therapy in several domains. Conclusion Adverse effects on QoL are seen in the first few months after surgery, but by 24 months these have largely resolved. Women considering surgery should be informed of these effects.
Published: 2021
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15. Observational cohort study to determine the degree and causes of variation in the rate of surgery or primary endocrine therapy in older women with operable breast cancer

Author: Alistair Ring, Charlene Martin, Anne Shrestha, Geoff Holmes, Kate Lifford, Deirdre Revill, Lynda Wyld, Jacqui Gath, Stephen J Walters, Katherine Emma Brain, Paul Richards, Malcolm Wr. Reed, Kieran Horgan, Rishi Parmeshwar, Tracy Green, T. Robinson, Jay Naik, Annaliza Todd, Sue Ward, Chris Holcombe, Tim Chater, Riccardo A. Audisio, Kwok-Leung Cheung, Kirsty Pemberton, Chris Murray, Jenna Morgan, Anthony Nettleship, Adrian Edwards, Richard Simcock, Maria Burton, J.T. Wright, and Helena Harder
Subjects: medicine.medical_specialty, Funnel plot, Hormone Replacement Therapy, Concordance, Breast Neoplasms, 030230 surgery, Logistic regression, Choice Behavior, Article, 03 medical and health sciences, Breast cancer, Elderly, 0302 clinical medicine, Case mix index, Surveys and Questionnaires, medicine, Humans, Prospective Studies, Prospective cohort study, Mastectomy, Aged, Aged, 80 and over, business.industry, Patient Selection, Age Factors, Patient Preference, General Medicine, Prognosis, medicine.disease, Confidence interval, Surgery, Oncology, Treatment variation, 030220 oncology & carcinogenesis, Primary endocrine therapy, Female, business, Follow-Up Studies, Cohort study
Abstract: Background: In the UK there is variation in the treatment of older women with breast cancer, with up to\ud 40% receiving primary endocrine therapy (PET), which is associated with inferior survival. Case mix and\ud patient choice may explain some variation in practice but clinician preference may also be important.\ud Methods: A multicentre prospective cohort study of women aged >70 with operable breast cancer. Patient characteristics (health status, age, tumour characteristics, treatment allocation and decision-making\ud preference) were analysed to identify whether treatment variation persisted following case-mix\ud adjustment. Expected case-mix adjusted surgery rates were derived by logistic regression using the\ud variables age, co-morbidity, tumour stage and grade. Concordance between patients’ preferred and\ud actual decision-making style was assessed and associations between age, treatment and decision-making\ud style calculated.\ud Results: Women (median age 77, range 70e102) were recruited from 56 UK breast units between 2013\ud and 2018. Of 2854/3369 eligible women with oestrogen receptor positive breast cancer, 2354 were\ud treated with surgery and 500 with PET. Unadjusted surgery rates varied between hospitals, with 23/56\ud units falling outside the 95% confidence intervals on funnel plots. Adjusting for case mix reduced, but did\ud not eliminate, this variation between hospitals (10/56 units had practice outside the 95% confidence\ud intervals). Patients treated with PET had more patient-centred decisions compared to surgical patients\ud (42.2% vs 28.4%, p < 0.001).\ud Conclusions: This study demonstrates variation in treatment selection thresholds for older women with\ud breast cancer. Health stratified guidelines on thresholds for PET would help reduce variation, although\ud patient preference should still be respected.
Published: 2021
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16. Bridging the Age Gap in breast cancer: Impact of chemotherapy on quality of life in older women with early breast cancer

Author: Lynda Wyld, Richard Simcock, Jacqui Gath, Alan Brennan, Deirdre Revell, Maria Burton, Riccardo A. Audisio, Jay Naik, Malcolm W.R. Reed, Kwok L. Cheung, Geoffrey Holmes, Charlene Martin, Annaliza Todd, Matthew Hatton, Tim Chater, Kirsty Pemberton, Stephen J Walters, Chris Holcombe, Matthew C Winter, Margot Gosney, Thompson G. Robinson, Kate Lifford, Adrian Edwards, A. Ring, Anne Shrestha, Kieran Horgan, Sue Ward, Juliet Wright, Alastair M. Thompson, Karen Collins, Rishi Parmeshwar, Nicolò Matteo Luca Battisti, Esther Herbert, Jenna Morgan, Age Gap Tmg, Tracey Green, and Mike Bradburn
Subjects: 0301 basic medicine, Quality of life, Cancer Research, medicine.medical_specialty, Nausea, medicine.medical_treatment, Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, medicine, Older patients, Humans, Prospective Studies, Adverse effect, Original Research, Aged, Aged, 80 and over, Chemotherapy, business.industry, Carcinoma, Ductal, Breast, Cancer, medicine.disease, Prognosis, humanities, Adjuvant chemotherapy, Carcinoma, Lobular, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Vomiting, Observational study, Female, medicine.symptom, business, Follow-Up Studies
Abstract: Introduction Older patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study. Materials and methods A prospective, multicentre, observational study of EBC patients ≥70 years old was conducted in 2013–2018 at 56 UK hospitals. Demographics, patient, tumour characteristics, treatments and adverse events were recorded. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires (EORTC-QLQ) C30, BR23 and ELD 15 plus the Euroqol-5D (eq-5d) over 24 months and analysed at each time point using baseline adjusted linear regression analysis and propensity score-matching. Results Three thousand and four hundred sixteen patients were enrolled in the study; 1520 patients undergoing surgery and who had high-risk EBC were included in this analysis. 376/1520 (24.7%) received chemotherapy. At 6 months, chemotherapy had a significant negative impact in several EORTC-QLQ-C30 domains, including global health score, physical, role, social functioning, cognition, fatigue, nausea/vomiting, dyspnoea, appetite loss, diarrhoea and constipation. Similar trends were documented on other scales (EORTC-QLQ-BR23, EORTC-QLQ-ELD15 and EQ-5D-5L). Its impact was no longer significant at 18–24 months in unmatched and matched cohorts. Conclusions The negative impact of chemotherapy on quality-of-life is clinically and statistically significant at 6 months but resolves by 18 months, which is crucial to inform decision-making for older patients contemplating chemotherapy. Trial registration number ISRCTN 46099296., Highlights • This is a multicentre, cohort study of 3416 women (aged >70 years) with breast cancer. • In older women with high-risk, early breast cancer, chemotherapy reduces quality of life. • The relevant affected domains include cognition, fatigue, physical, role and social functioning. • Chemotherapy QoL impacts are transient and largely resolve completely by 18–24 months.
Published: 2021

17. Age specific recruitment and retention to a large multicentre observational breast cancer trial in older women: The Age Gap Trial

Author: Malcolm W.R. Reed, Kwok-Leung Cheung, Jenna Morgan, Kirsty Pemberton, Thompson G. Robinson, Tim Chater, Maria Burton, Alistair Ring, Charlene Martin, Stephen J Walters, Annaliza Todd, Esther Herbert, Tracy Green, Riccardo A. Audisio, Lynda Wyld, Jacqui Gath, and Mike Bradburn
Subjects: media_common.quotation_subject, Staffing, Breast Neoplasms, Logistic regression, Article, Odds, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Activities of Daily Living, Medicine, Humans, 030212 general & internal medicine, media_common, Aged, Selection bias, business.industry, Cancer, Age bias, medicine.disease, United Kingdom, Clinical trial, Logistic Models, Oncology, Retention, Research Design, 030220 oncology & carcinogenesis, Observational study, Female, Recruitment, Geriatrics and Gerontology, business, Age distribution, Demography
Abstract: Introduction\ud \ud Recruitment and retention are two of the most important factors in successfully running clinical trials. Many trials encounter problems with both, causing delays or preventing study progress. These issues are greater in older adults and patients with cancer.\ud \ud \ud \ud Materials and methods\ud \ud We assessed recruitment and retention in a large, multicentre, observational breast cancer study in older female patients (>70 years, N = 3440). Data collected by the Age Gap study were used to assess rates of, and reasons for, patients not being recruited or retained. Statistical analysis assessed the impact of age as a predictor of recruitment and retention.\ud \ud \ud \ud Results\ud \ud Between February 2013 and June 2018, 6876 patients were screened and 3456 were consented across 56 United Kingdom (UK) breast units. Reasons for non-recruitment included ineligibility, clinician issues, staffing resource issues, patients' lack of interest or time and trial burden. In comparison with the age demographics of patients with breast cancer in the UK, women aged 70–75 years were over-represented compared to older age groups. Logistic regression demonstrated that older age significantly reduced the odds of consent (OR = 0.96, CI: 0.938–0.982; p < 0.001). Multivariate analysis showed that age (p < 0.001), markers of poor functional ability (Eastern Cooperative Oncology Group Performance Status (p = 0.011)) and instrumental activities of daily living (p = 0.026) were significant predictors of withdrawal.\ud \ud \ud \ud Discussion\ud \ud This study has demonstrated that selection and attrition bias for age are apparent despite a range of ‘age friendly’ study design measures. Exploration of the underlying reasons for this and development of measures to address this should be the focus of further research.
Published: 2021

18. Surgeon preference for treatment allocation in older people facing major gastrointestinal surgery: an application of the discrete choice experiment methodology

Author: Sarah L. Daniels, Jenna Morgan, Matthew J. Lee, Nyantara Wickramasekera, Susan Moug, Tim R. Wilson, Steven R. Brown, and Lynda Wyld
Subjects: Gastroenterology
Abstract: Variation in major gastrointestinal surgery rates in the older population suggests heterogeneity in surgical management. A higher prevalence of comorbidities, frailty and cognitive impairments in the older population may account for some variation. The aim of this study was to determine surgeon preference for major surgery versus conservative management in hypothetical patient scenarios based on key attributes.A survey was designed according to the discrete choice methodology guided by a separate qualitative study. Questions were designed to test for associations between key attributes (age, comorbidity, urgency of presentation, pathology, functional and cognitive status) and treatment preference for major gastrointestinal surgery versus conservative management. The survey consisting of 18 hypothetical scenarios was disseminated electronically to UK gastrointestinal surgeons. Binomial logistic regression was used to identify associations between the attributes and treatment preference.In total, 103 responses were received after 256 visits to the questionnaire site (response rate 40.2%). Participants answered 1847 out of the 1854 scenarios (99.6%). There was a preference for major surgery in 1112/1847 (60.2%) of all scenarios. Severe comorbidities (OR 0.001, 95% CI 0.000-0.030; P = 0.000), severe cognitive impairment (OR 0.001, 95% CI 0.000-0.033; P = 0.000) and age 85 years and above (OR 0.028, 95% CI 0.005-0.168; P = 0.000) were all significant in the decision not to offer major gastrointestinal surgery.This study has demonstrated variation in surgical treatment preference according to key attributes in hypothetical scenarios. The development of fitness-stratified guidelines may help to reduce variation in surgical practice in the older population.
Published: 2022

19. Abstract P6-05-17: Recruitment challenges in a UK surgical de-escalation study: preliminary qualitative research findings from the SMALL trial

Author: Stuart A. McIntosh, Charlotte E. Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Jenna Morgan, Sarah E. Pinder, Sarah Pirrie, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea, and Sangeetha Paramasivan
Subjects: Cancer Research, Oncology
Abstract: Background SMALL (ISRCTN 12240119) is a novel UK phase III multicentre randomised trial comparing vacuum-assisted excision (VAE) to surgery for small screen-detected breast cancers with biologically favourable characteristics. Acceptance by the clinical community and recruitment to SMALL was anticipated to be challenging as it involves randomisation, surgical de-escalation and minimally-invasive percutaneous treatment (VAE). A QuinteT Recruitment Intervention (QRI) has therefore been integrated throughout SMALL’s recruitment period, with the aim of optimising recruitment and informed consent. Methods The QRI in SMALL has involved the analysis of: a) screening log data b) written views from recruiters on the two treatments and their advantages/disadvantages c) in-depth semi-structured interviews with members of the Trial Management Group (TMG) and clinician-recruiters and d) audio-recordings of recruitment discussions with potentially eligible patients. Recruitment challenges were identified and addressed through the provision of written recruitment tips documents, and group and individual feedback sessions with recruiters. Results There was widespread support for the concept of the SMALL trial within the clinical community. Recruiters recognised the pioneering role of SMALL as the only current surgical de-escalation randomised trial in screen-detected breast cancer. Key recruitment challenges revolved around i) healthcare professionals (HCPs) who met patients early in the pathway providing information indicating that they were being referred for surgery (without mentioning SMALL or VAE), ii) concerns around the balance of de-escalation/escalation of different treatment modalities (e.g. some clinicians may prefer to de-escalate radiotherapy in preference to surgery in low-risk patients), iii) challenges in articulating equipoise in a surgical de-escalation trial, iv) patient preferences (primarily for surgery) and recruiter discomfort in exploring/addressing such preferences and v) fewer eligible patients than anticipated. QRI actions to overcome these issues included developing a tips document for HCPs meeting patients early in the pathway, highlighting the need to refrain from making treatment recommendations. A more generic tips document was also developed emphasising the importance of the early introduction of the study, provision of balanced information about both treatments, encouraging recruiters to engage with patients’ concerns and preferences, and adequate explanation of randomisation. Group and individual feedback sessions focussed on two key areas – articulating equipoise through balanced information provision, and considering optimal ways to explore patient preferences where they are expressed. Despite the many set-up and recruitment challenges that arose from opening at the start of the pandemic, SMALL has recruited 142 patients to date from 23 sites, with an approached to randomised patient ratio of ~50%. Conclusion SMALL is a novel surgical de-escalation study in breast cancer, which will provide critical evidence to support reductions in treatment of good prognosis disease. Using a range of qualitative methodology, the QRI has identified both broad support for the study within the clinical community, but has also identified barriers to recruitment at both clinician and patient level. These challenges have been addressed employing a range of methods, and the recruitment level and approach/randomised ratio shows the overall acceptability of this study to patients. Further work will involve interviews with patients, with a focus on their views on de-escalation, and further recruiter feedback sessions. Taken together, theis data will help inform the development and design of future de-escalation and treatment optimisation studies in breast cancer. SMALL is funded by the UK NIHR HTA programme, award 17/42/32 Citation Format: Stuart A. McIntosh, Charlotte E. Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Jenna Morgan, Sarah E. Pinder, Sarah Pirrie, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea, Sangeetha Paramasivan. Recruitment challenges in a UK surgical de-escalation study: preliminary qualitative research findings from the SMALL trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-17.
Published: 2023
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20. Patient satisfaction after simple mastectomy surgery for breast cancer: A service evaluation

Author: Hannah Everitt, Lynda Wyld, Charlene Martin, and Jenna Morgan
Subjects: Oncology, Surgery, General Medicine
Published: 2023
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21. Variation in endocrine therapy related adverse events with age and treatment agent in older women with oestrogen sensitive breast cancer

Author: Tanjim Quddus, Jenna Morgan, and Lynda Wyld
Subjects: Oncology, Surgery, General Medicine
Published: 2023
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22. Examining the barriers faced by female surgical trainees: a qualitative study

Author: Jenna Morgan, Lynda Wyld, and K Manning
Subjects: Male, Child care, Gender equality, Coping (psychology), Medical education, Students, Medical, Consultants, business.industry, Qualitative interviews, General Medicine, Unconscious bias, Equality and diversity, Less than full time, Medicine, Humans, Training, Surgery, Female, business, Qualitative research
Abstract: Introduction Today, women make up 56% of medical students, yet just 13% of surgical consultants – a number that has remained static since 2013. This qualitative study explored some of the barriers to female success in modern surgery. Methods Semistructured qualitative interviews were undertaken primarily with female surgical trainees to determine the barriers they face. Male trainees and training programme directors (TPDs) were also interviewed for triangulation. Results 20 interviews were performed (16 female trainees, 3 male trainees, and 1 TPD) between October 2019 and March 2020. Family pressures and becoming a mother were significant barriers for women training in surgery – a barrier that did not apply to male trainees who were fathers, often resulting in women choosing to train less than full time (LTFT). Unfortunately LTFT training presents further obstacles for female trainees. The set-up of the national training programme in surgery provides many non-gender-specific barriers, chiefly moving hospital every 6 months causing disrupted training and long commutes, disproportionately affecting females with child care responsibilities. Sexism and discrimination are still common, both from colleagues and patients. Many participants perceived inherent differences between genders in communication and methods for coping with stress. Conclusion Greater gender equality in surgery may be achieved by changes in the structure and organisation of training to reduce the tension between the professional role and the predominantly female-led role of raising children. Better equality and diversity training and awareness at all levels in surgery may help to mitigate some of the conscious and unconscious bias that still exists.
Published: 2021

23. EP.TH.602Exploring decision-making of healthcare professionals in patients with benign large non-pedunculated colonic polyps (BLNPCP) virtually using combined focus group and nominal group technique

Author: S Riley, Lynda Wyld, Jenna Morgan, L Wheldon, Matthew Lee, and Steven R Brown
Subjects: medicine.medical_specialty, Health professionals, business.industry, General surgery, Nominal group technique, medicine, Surgery, In patient, business, Focus group
Abstract: Aim We aimed to elicit key factors that influence healthcare professional decision-making when deciding treatment for BLNPCP. Background Benign large non-pedunculated colonic polyps (BLNPCP) may harbour covert malignancy and opinions differ about the optimal treatment modality. There are several options available, including endoscopic mucosal resection, endoscopic submucosal resection, combined endoscopic laparoscopic surgery and surgical resection. Despite widespread availability of endoscopic resection techniques, there are high rates of surgery in the UK. Methods Three focus groups of healthcare professionals, comprised of either consultant colorectal surgeons, nurse endoscopists and consultant gastroenterologists, were conducted virtually utilising the Nominal Group Technique. Meetings were recorded and transcribed verbatim. Themes were devolved using the framework approach for qualitative analysis. A priority-ranked list of factors influencing healthcare professional decision-making in this setting was generated. Results Five main themes were identified as influencing decision-making: Shared decision making (patient preference, informed consent); Patient factors (co-morbidity, age, life-expectancy); Polyp factors (Location, size, morphology, risk of cancer); Healthcare professionals (skill-set, personal preference); System factors (techniques availability locally, regional referral networks). Nominal Group Technique generated 55 items across the three focus groups. Nurses and gastroentologists ranked patient factors (particularly drug history and tolerance of procedure) and shared decision making (patient preference) more highly then surgeons. Surgeons placed greater emphasis on polyp factors particularly location and the risk of submucosal invasive carcinoma. Conclusion Decision making is complex and multifactorial. These results support the benefits of complex polyp MDTs and patient involvement in the decision-making. The complexity of decision-making may underpin wide variation in practice.
Published: 2021
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24. 626 Barriers Faced by Female Surgical Trainees – A Qualitative Study

Author: Jenna Morgan, Lynda Wyld, and K Manning
Subjects: Medical education, business.industry, Medicine, Surgery, business, Qualitative research
Abstract: Aim Today women make up 56% of medical students, yet just 12% of surgical consultants, a number that has remained static since 2013. This qualitative study aimed to explore the barriers to female success in modern surgery. Method Semi-structured qualitative interviews were undertaken primarily with female surgical trainees to determine the barriers they face. Male trainees and Training Programme Directors were also interviewed for triangulation. Results Nineteen interviews were performed (15 female trainees, 3 male trainees and 1 TPD) between October 2019 and March 2020. Family pressures and becoming a mother were significant barriers for women training in surgery, a barrier that did not apply to male trainees who were fathers, often resulting in women choosing to train less than full time (LTFT). Unfortunately, LTFT training presents further obstacles for female trainees. The set-up of the National training programme in surgery provides many non-gender specific barriers, chiefly moving hospital every 6 months resulting in disrupted training and long commutes. Sexism and discrimination are still common, both from colleagues and patients. Many participants perceived inherent differences between genders in communication and methods for coping with stress. Conclusions Greater gender equality in surgery may be achieved by changes in the structure and organisation of training to reduce the tension between the professional role and the predominantly female-led role of raising children. Better equality and diversity training and awareness at all levels in surgery may help to mitigate some of the conscious and unconscious bias that still exists.
Published: 2021
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25. Observational cohort study in older women with early breast cancer: Use of radiation therapy and impact on health-related quality of life and mortality

Author: Juliet Wright, Maria Burton, Jay Naik, Riccardo A. Audisio, Malcolm W.R. Reed, Kate Lifford, Tracy Green, Kieran Horgan, Tim Chater, Lynda Wyld, Mike Bradburn, Jenna Morgan, Rishi Parmeshwar, Jacqui Gath, Nicolò Matteo Luca Battisti, Geoffrey Holmes, Charlene Martin, Deirdre Revell, Adrian Edwards, Karen Collins, Stephen J Walters, Matthew C Winter, Annaliza Todd, Esther Herbert, Margot Gosney, Kwok-Leung Cheung, A. Ring, Kirsty Pemberton, Thompson G. Robinson, Alastair M. Thompson, Sue Ward, Chris Holcombe, Richard Simcock, Alan Brennan, and Matthew Hatton
Subjects: medicine.medical_specialty, medicine.medical_treatment, Breast Neoplasms, Mastectomy, Segmental, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Mastectomy, Aged, Early breast cancer, business.industry, Cancer, Hematology, medicine.disease, Comorbidity, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Female, Radiotherapy, Adjuvant, Observational study, business, Cohort study
Abstract: Background\ud \ud Radiotherapy reduces in-breast recurrence risk in early breast cancer (EBC) in older women. This benefit may be small and should be balanced against treatment effect and holistic patient assessment. This study described treatment patterns according to fitness and impact on health-related quality-of-life (HRQoL).\ud \ud \ud \ud Methods\ud \ud A multicentre, observational study of EBC patients aged ≥ 70 years, undergoing breast-conserving surgery (BCS) or mastectomy, was undertaken. Associations between radiotherapy use, surgery, clinico-pathological parameters, fitness based on geriatric parameters and treatment centre were determined. HRQoL was measured using the European Organisation for the Research and Treatment of Cancer (EORTC) questionnaires.\ud \ud \ud \ud Results\ud \ud In 2013–2018 2811 women in 56 UK study centres underwent surgery with a median follow-up of 52 months. On multivariable analysis, age and tumour risk predicted radiotherapy use. Among healthier patients (based on geriatric assessments) with high-risk tumours, 534/613 (87.1%) having BCS and 185/341 (54.2%) having mastectomy received radiotherapy. In less fit individuals with low-risk tumours undergoing BCS, 149/207 (72.0%) received radiotherapy. Radiotherapy effects on HRQoL domains, including breast symptoms and fatigue were seen, resolving by 18 months.\ud \ud \ud \ud Conclusion\ud \ud Radiotherapy use in EBC patients ≥ 70 years is affected by age and recurrence risk, whereas geriatric parameters have limited impact regardless of type of surgery. There was geographical variation in treatment, with some fit older women with high-risk tumours not receiving radiotherapy, and some older, low-risk, EBC patients receiving radiotherapy after BCS despite evidence of limited benefit. The impact on HRQoL is transient.
Published: 2021

26. Predicting postoperative complications and their impact on quality of life and functional status in older patients with breast cancer

Author: Annelieke Lemij, Willeke van der Plas-Krijgsman, Esther Bastiaannet, Jos Merkus, Thijs van Dalen, Annelie Vulink, Leander van Gerven, Onno Guicherit, Eugenie Linthorst-Niers, Titia Lans, Carmen van der Pol, Lynda Wyld, Jenna Morgan, Johanneke Portielje, Nienke de Glas, and Gerrit Jan Liefers
Subjects: Oncology, Surgery, General Medicine
Published: 2022
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27. Adjuvant Chemotherapy for Breast Cancer in Older Women: An Analysis of Retrospective English Cancer Registration Data

Author: Lynda Wyld, Jenna Morgan, Geoffrey Holmes, Alistair Ring, Malcolm W.R. Reed, Karen Collins, Sue Ward, John Broggio, and Paul Richards
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, Breast Neoplasms, Disease, Logistic regression, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Registries, Aged, Retrospective Studies, Chemotherapy, business.industry, Hazard ratio, Cancer, medicine.disease, Survival Analysis, Confidence interval, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Life expectancy, Female, business
Abstract: Aims\ud Adjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data.\ud \ud Materials and methods\ud Cancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation.\ud \ud Results\ud In total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67–0.81).\ud \ud Discussion\ud Chemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference.
Published: 2019
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28. Wire- and magnetic-seed-guided localization of impalpable breast lesions: iBRA-NET localisation study

Author: Rajiv V, Dave, Emma, Barrett, Jenna, Morgan, Mihir, Chandarana, Suzanne, Elgammal, Nicola, Barnes, Amtul, Sami, Tahir, Masudi, Sue, Down, Chris, Holcombe, Shelley, Potter, Santosh K, Somasundaram, Matthew, Gardiner, Senthurun, Mylvaganam, Anthony, Maxwell, James, Harvey, and W, Lambert
Subjects: Breast Neoplasms/pathology, Magnets/adverse effects, Margins of Excision, Breast Neoplasms, Middle Aged, Mastectomy, Segmental, Postoperative Complications, Fiducial Markers, Mastectomy, Segmental/adverse effects, Magnets, Humans, Surgery, Female, Prospective Studies, Aged, Neoplasm Staging
Abstract: Background Wire localization is historically the most common method for guiding excision of non-palpable breast lesions, but there are limitations to the technique. Newer technologies such as magnetic seeds may allow some of these challenges to be overcome. The aim was to compare safety and effectiveness of wire and magnetic seed localization techniques. Methods Women undergoing standard wire or magnetic seed localization for non-palpable lesions between August 2018 and August 2020 were recruited prospectively to this IDEAL stage 2a/2b platform cohort study. The primary outcome was effectiveness defined as accurate localization and removal of the index lesion. Secondary endpoints included safety, specimen weight and reoperation rate for positive margins. Results Data were accrued from 2300 patients in 35 units; 2116 having unifocal, unilateral breast lesion localization. Identification of the index lesion in magnetic-seed-guided (946 patients) and wire-guided excisions (1170 patients) was 99.8 versus 99.1 per cent (P = 0.048). There was no difference in overall complication rate. For a subset of patients having a single lumpectomy only for lesions less than 50 mm (1746 patients), there was no difference in median closest margin (2 mm versus 2 mm, P = 0.342), re-excision rate (12 versus 13 per cent, P = 0.574) and specimen weight in relation to lesion size (0.15 g/mm2versus 0.138 g/mm2, P = 0.453). Conclusion Magnetic seed localization demonstrated similar safety and effectiveness to those of wire localization. This study has established a robust platform for the comparative evaluation of new localization devices.
Published: 2021
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29. Treatment choices for older women with primary operable breast cancer and cognitive impairment: Results from a prospective, multicentre cohort study

Author: Kirsty Pemberton, Thompson G. Robinson, Annaliza Todd, Stephen J Walters, Adrian Edwards, Lynda Wyld, Malcolm W.R. Reed, Sue Ward, Jacqui Gath, Karen Collins, Deirdre Revell, Alistair Ring, Charlene Martin, Riccardo A. Audisio, Kwok-Leung Cheung, Jenna Morgan, Maria Burton, Esther Herbert, Geoffrey Holmes, Kate Lifford, Mike Bradburn, Tracy Green, Tim Chater, and Anne Shrestha
Subjects: medicine.medical_specialty, medicine.medical_treatment, Breast Neoplasms, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, Humans, Dementia, Cognitive Dysfunction, Prospective Studies, 030212 general & internal medicine, Cognitive impairment, Aged, Chemotherapy, business.industry, Standard treatment, medicine.disease, Radiation therapy, Oncology, Severe dementia, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, Geriatrics and Gerontology, business, Cohort study
Abstract: Objectives\ud \ud The presence of dementia co-existing with a diagnosis of breast cancer may render management more challenging and have a substantial impact on oncological outcomes. The aim of this study was to examine the treatment and outcomes of older women with co-existing cognitive impairment and primary breast cancer.\ud \ud \ud Materials and methods\ud \ud A prospective, multicentre UK cohort study of women aged 70 years or over with primary operable breast cancer. Patients with and without cognitive impairment were compared to assess differences in treatment and survival outcomes.\ud \ud \ud Results\ud \ud In total, 3416 women were recruited between 2013 and 2018. Of these, 478 (14%) had a diagnosis of dementia or cognitive impairment, subcategorised as mild, moderate and severely impaired. Up to 85% of women with normal cognition underwent surgery compared to 74%, 61% and 40% with mild, moderate, and severe impairment (p = 0.001). Among women at higher risk of recurrence, the uptake of chemotherapy was 25% for cognitively normal women compared to 20%, 22% and 12% for mild, moderate and severe impairment groups (p = 0.222). Radiotherapy use was similar in the subgroups. Although patients with cognitive impairment had shorter overall survival (HR: 2.10, 95% CI: 1.77–2.50, p < 0.001), there were no statistically significant differences in breast cancer specific or progression-free survival.\ud \ud \ud Conclusion\ud \ud Cognitive impairment appears to play a significant part in deciding how to treat older women with breast cancer. Standard treatment may be over-treatment for some women with severe dementia and careful consideration must be given to a more tailored approach in these women.
Published: 2021

30. Gendered pathways from strain to delinquency during adolescence

Author: Jenna Morgan Savage
Published: 2021
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31. 50 Landmark Papers Every Breast Surgeon Should Know

Author: Lynda Wyld, Ramsey Cutress, Jenna Morgan, Lynda Wyld, Ramsey Cutress, and Jenna Morgan
Subjects: Breast--Cancer--Surgery
Abstract: There has been an exponential increase in the volume and quality of published research relating to breast disease over the past decades. This book identifies the 50 key scientific articles in the field of breast disease and breast surgery and examines their importance and impact on current clinical care.Among thousands of articles, a small fraction are truly'game changing'. Such studies form the foundations of breast surgery today, and the selection of papers within this book provide the 50 landmark papers every 21st-century breast surgeon needs to know. A commentary to each carefully selected paper explains why these papers are so important, thus providing every surgeon with the foundation stones of knowledge in this fast-moving area.A valuable reference not only to the established surgeon, but also to breast surgery residents and trainees, as well as to more experienced surgeons as they continue to learn new techniques and approaches and to improve their knowledge of breast disease and treatments. The papers provide an evidence-based resource for those surgeons preparing for professional exams and may inspire clinicians to produce new research.
Published: 2024

32. The breast

Author: Jenna Morgan and Lynda Wyld
Published: 2021
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33. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life

Author: Kate Lifford, Alan Brennan, Jay Naik, Richard Simcock, Julietta Patnick, Lynda Wyld, Kirsty Pemberton, Alastair M. Thomson, Jacqui Gath, Maria Burton, Thompson G. Robinson, Kwok L. Cheung, Riccardo A. Audisio, Jenna Morgan, Matt Winter, Alistair Ring, Deirdre Revell, Matthew Hatton, Charlene Martin, Sue Ward, Stephen J Walters, Malcolm W.R. Reed, Geoffrey Holmes, Chris Holcombe, Juliet Wright, Margot Gosney, Kieran Horgan, Adrian Edwards, Rishi Parmeshwar, Tracy Green, Annaliza Todd, Anne Shrestha, Tim Chater, Karen Collins, Esther Herbert, and Mike Bradburn
Subjects: 0301 basic medicine, Quality of life, Cancer Research, medicine.medical_specialty, Survival, Breast Neoplasms, Adjuvant endocrine therapy, Breast cancer, Older women, Patient-centred outcomes, Primary endocrine therapy, Propensity score matching, Quality of life, Surgery, Survival, Stratified analysis, Older women, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Adjuvant endocrine therapy, Risk Factors, Propensity score matching, Medicine, Humans, Prospective Studies, Propensity Score, Aged, Aged, 80 and over, business.industry, Hazard ratio, medicine.disease, Comorbidity, Clinical Trial, Survival Analysis, Confidence interval, Surgery, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Primary endocrine therapy, Female, business, Patient-centred outcomes, Cohort study
Abstract: Background Age-related breast cancer treatment variance is widespread with many older women having primary endocrine therapy (PET), which may contribute to inferior survival and local control. This propensity-matched study determined if a subgroup of older women may safely be offered PET. Methods Multicentre, prospective, UK, observational cohort study with propensity-matched analysis to determine optimal allocation of surgery plus ET (S+ET) or PET in women aged ≥70 with breast cancer. Data on fitness, frailty, cancer stage, grade, biotype, treatment and quality of life were collected. Propensity-matching (based on age, health status and cancer stage) adjusted for allocation bias when comparing S+ET with PET. Findings A total of 3416 women (median age 77, range 69–102) were recruited from 56 breast units—2854 (88%) had ER+ breast cancer: 2354 had S+ET and 500 PET. Median follow-up was 52 months. Patients treated with PET were older and frailer than patients treated with S+ET. Unmatched overall survival was inferior in the PET group (hazard ratio, (HR) 0.27, 95% confidence interval (CI) 0.23–0.33, P 90 years or >85 with comorbidities or frailty) individualised decision making regarding PET versus S+ET may be appropriate and safe to offer. The Age Gap online decision tool may support this decision-making process (https://agegap.shef.ac.uk/). Trial registration number ISRCTN: 46099296., Highlights • Propensity matched study of women >70 with breast cancer comparing surgery or PET • Unmatched analysis found surgery improves overall & disease-specific survival. • Matched analysis (stage, age, health, frailty) found similar disease-specific survival • Surgery led to adverse events in 19% & negative impacts on QoL and physical function • Less fit women >85 may be offered PET to reduce morbidity, without survival detriment
Published: 2021

34. SMALL: Open surgery versus minimally invasive vacuum-assisted excision for small screen-detected breast cancers

Author: Stuart McIntosh, Charlotte E. Coles, Carmel Conefrey, David John Dodwell, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Jenna Morgan, Sangeetha Paramasivan, Sarah E. Pinder, Sarah Pirrie, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, and Dan Rea
Subjects: Cancer Research, Oncology
Abstract: TPS614 Background: Mammographic screening programmes reduce breast cancer mortality but detect many small tumours with favourable biology which may not progress. These are treated with surgery and adjuvant therapies, but associated morbidities mean there is a need to reduce overtreatment. Minimally invasive treatments such as vacuum-assisted excision (VAE) have been described but there is no prospective randomised evidence to support their routine use. SMALL (ISRCTN 12240119) is designed to establish the feasibility of using VAE to treat small tumours detected within the UK NHS Breast Screening Programme (BSP). Methods: Phase III multicenter randomized trial comparing surgery with VAE for screen-detected good prognosis cancers. Eligibility criteria are age ≥47 years, unifocal grade 1 tumors (maximum diameter 15mm), strongly ER/PR+ve and HER2-ve, with negative axillary staging. Patients are randomized 2:1 to VAE or surgery, with no axillary surgery in the VAE arm. Excision is assessed radiologically, and if incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm. Coprimary end-points are: (1) Non-inferiority comparison of the requirement for a second procedure. (2) Single-arm analysis of local recurrence (LR) at 5 years after VAE. Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure, ensuring sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. The DMC will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A QuinteT Recruitment Intervention (QRI) is integrated throughout SMALL to optimize recruitment and informed consent. Recruitment challenges are identified by analyzing recruiter/patient interviews, audio-recordings of trial discussions, and by review of screening, eligibility and recruitment data and study documentation. Solutions are developed collaboratively, including recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019, but recruitment halted for 5 months due to COVID-19. At 11th February 2022, 91 patients had been recruited from 22 centers, with an approached/consented ration of 50%. Drawing from preliminary QRI findings, a recruitment tips document has been circulated (on discussing SMALL, providing balanced information on treatment options and explaining randomization). Individual recruiter feedback has commenced, with wider feedback planned shortly. Conclusion: Despite pandemic-related challenges, SMALL has excellent recruitment to date and is expected to have a global impact on treatment of screen-detected breast cancer. Clinical trial information: 12240119.
Published: 2022
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35. Bridging the Age Gap: a prognostic model that predicts survival and aids in primary treatment decisions for older women with oestrogen receptor-positive early breast cancer

Author: Sue Ward, Geoffrey Holmes, Karen Collins, Jenna Morgan, John Broggio, Malcolm W.R. Reed, Lynda Wyld, and Paul Richards
Subjects: Oncology, medicine.medical_specialty, Estrogen receptor, Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Acquired immunodeficiency syndrome (AIDS), Clinical Decision Rules, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, Early breast cancer, Models, Statistical, business.industry, Age Factors, Cancer, Prognosis, medicine.disease, Cancer registry, Receptors, Estrogen, 030220 oncology & carcinogenesis, Prognostic model, Female, Surgery, Primary treatment, business
Abstract: A prognostic model was developed and validated using cancer registry data. This underpins an online decision support tool, informing primary treatment choice for women aged 70 years or older with hormone receptor-positive early breast cancer.Data from women diagnosed between 2002 and 2010 in the English Northern and Yorkshire and West Midlands regions were used to develop the model. Primary treatment options of surgery with adjuvant endocrine therapy or primary endocrine therapy were compared. Models predicting the hazard of breast cancer-specific mortality and hazard of other-cause mortality were combined to derive survival probabilities. The model was validated externally using data from the Eastern Cancer Registration and Information Centre.The model was developed using data from 23 842 women, and validated externally on a data set from 14 526 patients. The overall model calibration was good. At 2 and 5 years, predicted mortality from breast cancer and other causes differed from the observed rate by less than 1 per cent. At 5 years, there were slight overpredictions in breast cancer mortality (2629 predicted versus 2556 observed deaths; P = 0·142) and mortality from all causes (6399 versus 6320 respectively; P = 0·583). The discrepancy varied between subgroups. Model discrimination was 0·75 or above for all mortality measures.A prognostic model for older women with oestrogen receptor-positive early breast cancer was developed and validated in the present study. This forms a basis for an online decision support tool (https://agegap.shef.ac.uk/).Se ha desarrollado y validado un modelo pronóstico utilizando datos del registro de cáncer. Ello ha permitido ofrecer una herramienta online para facilitar la toma de decisiones respecto a la elección del tratamiento inicial en mujeres mayores de 70 años con cáncer de mama precoz y receptores de hormonas positivos. MÉTODOS: Se incluyeron un total de 23.842 mujeres, diagnosticadas entre 2002 y 2010 en las regiones del Norte, Yorkshire y West Midlands inglesas que cumplieron con los criterios de inclusión. Se compararon dos opciones de tratamiento: cirugía primaria asociada a tratamiento endocrino adyuvante o tratamiento primario endocrino. Para estimar la probabilidad de supervivencia se combinaron modelos predictivos para el riesgo de mortalidad específica por cáncer de mama y para el riesgo de mortalidad por otras causas. Se realizó una validación externa con datos del Eastern Cancer Registration and Information Center (n = 14.526).La calibración global del modelo fue buena. A los 2 y 5 años, la mortalidad anticipada por cáncer de mama y por otras causas difería de la observada en menos del 1%. A los 5 años, hubo una ligera sobrevaloración de la predicción de mortalidad por cáncer de mama (prevista versus real: 2.629 versus 2.556, P = 0,78) y de la mortalidad por todas las causas (6.399 versus 6.320, P = 0,14). Esta discrepancia varió entre subgrupos. La capacidad discriminativa del modelo fue del 0,75 o superior para todas las medidas de mortalidad. CONCLUSIÓN: En este estudio, se desarrolló y validó un modelo pronóstico para mujeres mayores con cáncer de mama precoz positivo para receptores de estrógenos. Esta herramienta que facilita la toma de decisiones está disponible online (https://agegap.shef.ac.uk/).
Published: 2020

36. Special issues for older women with primary breast cancer

Author: Ruth M. Parks, Lynda Wyld, Kwok-Leung Cheung, Jenna Morgan, and Yasmin Jauhari
Subjects: medicine.medical_specialty, education.field_of_study, West midlands, business.industry, Population, Key issues, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Oncology, Radiology Nuclear Medicine and imaging, 030220 oncology & carcinogenesis, Family medicine, medicine, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Primary breast cancer, education, business, skin and connective tissue diseases, Patient factors
Abstract: It is estimated that the number of older women living with breast cancer will quadruple by 2040 [1]. Despite this, there is a lack of strong evidence and guidelines to support management decisions for this population.\ud \ud This article has evolved from a conference session on this subject, held at the 2020 UK Interdisciplinary Breast Cancer Symposium (UKIBCS; West Midlands, UK, 27–28 January 2020) [2]. The UKIBCS is a biennial meeting for all those with an active interest in breast cancer research and treatment, hosted by the charity Breast Cancer Now (London, UK), in collaboration with eight other breast cancer focused specialist societies.\ud \ud In this editorial, we discuss key issues in the management of breast cancer in older women, which include both tumor and patient factors. We also review current national initiatives to tackle these issues and summarize ongoing work in this field.
Published: 2020

37. The care of older cancer patients in the United Kingdom

Author: Nicola de Liguori Carino, Kwok-Leung Cheung, Richard Simcock, Ruth M. Parks, Sarah Danson, Neil Bayman, Lynda Wyld, Fiammetta Ugolini, Eleri Davies, Gary J. Doherty, Anita Parbhoo, Malcolm W.R. Reed, Daniel Swinson, Kirsty Colquhoun, Juliet Wright, Tania Kalsi, Michael J. Lind, Anna Lewis, Pippa Corrie, Gordana Babic-Illamn, Eleanor Smith, Simone Basile, Cassandra Ng, John Moore, Zoe Merchant, Alastair Greystoke, Danielle Harari, Rob Morris, Rachel Jones, Jenna Morgan, Anthea Cree, R. Young, Kyle Crawford, Mark Baxter, Lisa Jane Rodgers, and Fabio Gomes
Subjects: Gerontology, Cancer Research, Population ageing, business.industry, Biological age, Cancer, Review, medicine.disease, older patients, United Kingdom, Health problems, Quality of life (healthcare), Oncology, Older patients, Geriatric oncology, Daily practice, medicine, cancer, business, geriatric oncology
Abstract: The ageing population poses new challenges globally. Cancer care for older patients is one of these challenges, and it has a significant impact on societies. In the United Kingdom (UK), as the number of older cancer patients increases, the management of this group has become part of daily practice for most oncology teams in every geographical area. Older cancer patients are at a higher risk of both under- and over-treatment. Therefore, the assessment of a patient's biological age and effective organ functional reserve becomes paramount. This may then guide treatment decisions by better estimating a prognosis and the risk-to-benefit ratio of a given therapy to anticipate and mitigate against potential toxicities/difficulties. Moreover, older cancer patients are often affected by geriatric syndromes and other issues that impact their overall health, function and quality of life. Comprehensive geriatric assessments offer an opportunity to identify and address health problems which may then optimise one's fitness and well-being. Whilst it is widely accepted that older cancer patients may benefit from such an approach, resources are often scarce, and access to dedicated services and research remains limited to specific centres across the UK. The aim of this project is to map the current services and projects in the UK to learn from each other and shape the future direction of care of older patients with cancer.
Published: 2020

38. Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies

Author: Lynda Wyld, Sarah Danson, Jayan George, James L. Kirkland, Tamara Tchkonia, Ilaria Bellantuono, Olivia Turner, Jenna Morgan, and Fiona Foss
Subjects: 0301 basic medicine, Senescence, Cancer Research, senescence, medicine.medical_treatment, Review, Disease, frailty, lcsh:RC254-282, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, medicine, cancer, senotherapies, geriatric oncology, Senolytic, Navitoclax, business.industry, aging, Cancer, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Telomere, Radiation therapy, 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, senolytics, Cancer research, business
Abstract: Cellular senescence is a key component of human aging that can be induced by a range of stimuli, including DNA damage, cellular stress, telomere shortening, and the activation of oncogenes. Senescence is generally regarded as a tumour suppressive process, both by preventing cancer cell proliferation and suppressing malignant progression from pre-malignant to malignant disease. It may also be a key effector mechanism of many types of anticancer therapies, such as chemotherapy, radiotherapy, and endocrine therapies, both directly and via bioactive molecules released by senescent cells that may stimulate an immune response. However, senescence may contribute to reduced patient resilience to cancer therapies and may provide a pathway for disease recurrence after cancer therapy. A new group of drugs, senotherapies, (drugs which interact with senescent cells to interfere with their pro-aging impacts by either selectively destroying senescent cells (senolytic drugs) or inhibiting their function (senostatic drugs)) are under active investigation to determine whether they can enhance the efficacy of cancer therapies and improve resilience to cancer treatments. Senolytic drugs include quercetin, navitoclax, and fisetin and preclinical and early phase clinical data are emerging of their potential role in cancer treatments, although none are yet in routine use clinically. This article provides a review of these issues.
Published: 2020

39. Women’s Decision Making on Birthing Choices in the Private Sector of Namibia: Midwives’ Perspectives

Author: Cornelle Young, Sarah Mlambo, and Jenna Morgan-Cramer
Subjects: Advanced and Specialized Nursing, business.industry, media_common.quotation_subject, Public sector, Context (language use), Private sector, Nonprobability sampling, Nursing, Maternity and Midwifery, Public hospital, Institution, Childbirth, Sociology, business, Qualitative research, media_common
Abstract: In this study, the views of midwives regarding decision making in the Namibian private sector hospital labour wards were investigated with the aim of understanding the reasons for the high prevalence of caesarean sections in the Namibian private sector. The study objective was to determine the views of midwives about how women in the private sector labour wards decide on a birthing method. A qualitative design with an exploratory approach was followed, with the application of purposive sampling in the selection of research participants. Seven individual and in-depth interviews with midwives were conducted in two private hospitals in Windhoek. Data analysis was done using the six steps proposed by Creswell. Findings indicated that decision making depended on the woman, the doctor and the institution. Aspects such as the midwife’s relationship with the doctor, as well as the pregnant woman and the institution have an influence on such decisions made. Furthermore, the trust among and between health professionals, the availability of policies and guidelines, as well as the information received during antenatal care also affect the choice. It was found that women are not well informed about the choices they have for childbirth, the advantages and disadvantages of the chosen mode of birthing, as well as what to expect during the active stages of labour. In conclusion, decision making in the labour wards is important as it determines the birthing method outcome for every woman in the labour ward. Further studies need to be done in the same context and public hospital settings, to explore the dynamics in the public sector.
Published: 2020
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40. Long-term outcomes of latissimus dorsi flap breast reconstructions: A single-centre observational cohort study with up to 12 years of follow up

Author: Nazar Kazzazi, S. Nayak, Haley Hocking, Shazia Khan, Kadappa Kolar, Lynda Wyld, Kathryn Rigby, Jenna Morgan, Emma MacInnes, Clare Rogers, Ghulam Wattoo, and Olumuyiwa Olubowale
Subjects: Adult, medicine.medical_specialty, Esthetics, medicine.medical_treatment, Mammaplasty, Breast Neoplasms, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Surveys and Questionnaires, medicine, Humans, Latissimus dorsi flap, Adverse effect, Mastectomy, Aged, Retrospective Studies, business.industry, Chronic pain, Middle Aged, medicine.disease, United Kingdom, Surgery, Radiation therapy, Patient Satisfaction, 030220 oncology & carcinogenesis, Superficial Back Muscles, Female, Implant, business, Breast reconstruction, Cohort study, Follow-Up Studies
Abstract: Summary Introduction The Latissimus Dorsi Myocutaneous Flap (LDMF) is used in post-mastectomy reconstruction. This study has evaluated long-term (up to 12 years) surgical- and patient-reported outcomes from LDMF procedures. Method A retrospective analysis of consecutive LDMF procedures in two UK hospitals, performed between 2006 and 2016. Case notes were reviewed for indications and outcomes. Patients were sent the BREAST-QⓇ survey by post. Outcomes, including surgical adverse events, revision, and implant loss rates, were correlated with patient risk factors. Results A BREAST-Q was posted to 199/248 LDMF patients in 2018, (excluding 49 patients due to death, reduced cognitive function and incorrect coding) of whom 77 patients responded (38.7%). In 188 cases (representing 208 LDMFs), surgical outcomes were assessable. Median time since LDMF surgery was 7 years (range 2–12). Rates of acute implant loss were 9/139 (6.4%), flap necrosis 7/208 (3.4%), shoulder stiffness 4/208 (1.9%), chronic pain 24/208 (11.5%) and unplanned revision surgery 13/208 (7%). Median satisfaction levels were high with 78% of patients satisfied with treatment outcomes, 65% of patients satisfied with their breasts, 71% of patients satisfied psychosocially and 75% of patients satisfied with their chest. Receipt of radiotherapy was not associated with a higher risk of flap necrosis or capsule formation. Conclusion Long-term follow-up of a large cohort of LDMF reconstruction patients show relatively low levels of adverse events and unplanned revision surgery and high patient satisfaction, which demonstrates how temporally robust the technique is. With the rise in popularity of acellular dermal matrix reconstructions, the LDMF has relatively fallen out of favour but its potential in primary and delayed reconstruction is demonstrated.
Published: 2020

41. Barriers Faced by Female Surgical Trainees in the United Kingdom – A Qualitative Study

Author: Jenna Morgan, Katharine Manning, and Lynda Wyld
Subjects: Oncology, Surgery, General Medicine
Published: 2022
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42. A prospective cohort study to analyse the effect of socioeconomic deprivation on breast cancer stage at diagnosis, treatment allocation and outcomes in older women in the United Kingdom

Author: George Tresilian, Jenna Morgan, Lynda Wyld, Malcolm Reed, Charlene Martin, Timothy Chater, Kirsty Pemberton, Kwok Cheung Leung, Riccardo Audisio, Alastair Thompson, Kieran Horgan, and Chris Holcombe
Subjects: Oncology, Surgery, General Medicine
Published: 2022
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43. Outcomes from complex oncoplastic breast surgery in UK women over the age of 70. Analysis of data from the Age Gap cohort study

Author: Ratul Quddus, Jenna Morgan, Malcolm W. Reed, Kwok-Leung Cheung, Riccardo Audisio, and Lynda Wyld
Subjects: Oncology, Surgery, General Medicine
Published: 2022
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44. Systematic review of selection for and outcomes from post mastectomy breast reconstruction in older women (over age 60) with breast cancer

Author: Ratul Quddus, Jenna Morgan, and Lynda Wyld
Subjects: Oncology, Surgery, General Medicine
Published: 2022
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45. National survey of surgeon practice in the assessment and optimisation of older adults facing major gastrointestinal surgery

Author: Lynda Wyld, Matthew Lee, Tim Wilson, Steven H. Brown, Maria Burton, Susan Moug, Jenna Morgan, and Sarah Daniels
Subjects: medicine.medical_specialty, Oncology, business.industry, General surgery, Medicine, Surgery, General Medicine, business
Published: 2021
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46. Critical care admission following elective surgery was not associated with survival benefit

Author: Kahan, Brennan C., Desponia, Koulenti, Kostoula, Arvaniti, Vanessa, Beavis, Douglas, Campbell, Matthew, Chan, Rui, Moreno, Pearse, Rupert M., Scott, Beattie, Pierre-Alain, Clavien, Nicolas, Demartines, Lee, A Fleisher, Mike, Grocott, James, Haddow, Andreas, Hoeft, Peter, Holt, Naomi, Pritchard, Andrew, Rhodes, Duminda, Wijeysundera, Matt, Wilson, Tahania, Ahmed, Kirsty, Everingham, Russell, Hewson, Marta, Januszewska, Rupert, M Pearse, Mandeep-Kaur, Phull, Richard, Halliwell, Mark, Shulman, Paul, Myles, Werner, Schmid, Michael, Hiesmayr, Patrick, Wouters, Stefan de Hert, Suzana, Lobo, Xiangming, Fang, Lars, Rasmussen, Emmanuel, Futier, Matthieu, Biais, Aurélien, Venara, Karem, Slim, Michael, Sander, Despoina, Koulenti, Mathew, Chan, Atul, Kulkarni, Susilo, Chandra, Aida, Tantri, Emad, Geddoa, Muntadhar, Abbas, Giorgio Della Rocca, Datin, Sivasakthi, Marzida, Mansor, Pastor, Luna, Arthur, Bouwman, Wolfgang, Buhre, Tim, Short, Tunde, Osinaike, Ricardo, Matos, Ioana, Grigoras, Mikhail, Kirov, Denis, Protsenko, Bruce, Biccard, Cesar, Aldecoa, Michelle, Chew, Christoph, Hofer, Martin, Hubner, James, Ditai, Tamas, Szakmany, Lee, Fleisher, Marissa, Ferguson, Michael, Macmahon, Ritchie, Cherian, Helen, Currow, Kathirgamanathan, Kanathiban, David, Gillespie, Edward, Pathmanathan, Katherine, Phillips, Jenifer, Reynolds, Joanne, Rowley, Jeanene, Douglas, Ross, Kerridge, Sameer, Garg, Michael, Bennett, Megha, Jain, David, Alcock, Nico, Terblanche, Rochelle, Cotter, Kate, Leslie, Marcelle, Stewart, Nicolette, Zingerle, Antony, Clyde, Oliver, Hambidge, Adam, Rehak, Sharon, Cotterell, Wilson Binh Quan Huynh, Timothy, Mcculloch, Erez, Ben-Menachem, Thomas, Egan, Jennifer, Cope, Paul, Fellinger, Simone, Haselberger, Caroline, Holaubek, Paul, Lichtenegger, Florian, Scherz, Franz, Hoffer, Veronika, Cakova, Andreas, Eichwalder, Norbert, Fischbach, Reinhold, Klug, Elisabeth, Schneider, Martin, Vesely, Reinhart, Wickenhauser, Karl Gernot Grubmueller, Marion, Leitgeb, Friedrich, Lang, Nancy, Toro, Marlene, Bauer, Friedrich, Laengle, Thomas, Mayrhofer, Christian, Buerkle, Karin, Forstner, Reinhard, Germann, Harald, Rinoesl, Elke, Schindler, Ernst, Trampitsch, Gerhard, Fritsch, Christian, Szabo, Jawad, Bidgoli, Hans, Verdoodt, Patrice, Forget, David, Kahn, Fernande, Lois, Mona, Momeni, Caroline, Prégardien, Audrey, Pospiech, Arnaud, Steyaert, Laurent, Veevaete, Dirk De Kegel, Karen De Jongh, Luc, Foubert, Carine, Smitz, Marcel, Vercauteren, Jan, Poelaert, Veerle Van Mossevelde, Jacques, Abeloos, Stefaan, Bouchez, Marc, Coppens, Luc De Baerdemaeker, Isabel, Deblaere, Ann De Bruyne, Stefan De Hert, Kristine, Fonck, Bjorn, Heyse, Tom, Jacobs, Koen, Lapage, Anneliese, Moerman, Martine, Neckebroek, Aliaksandra, Parashchanka, Nathalie, Roels, Nancy Van Den Eynde, Michael, Vandenheuvel, Jurgen Van Limmen, Ann, Vanluchene, Caroline, Vanpeteghem, Piet, Wyffels, Christel, Huygens, Punitha, Vandenbempt, Marc Van de Velde, Dimitri, Dylst, Bruno, Janssen, Evelien, Schreurs, Fábia Berganton Aleixo, Keulle, Candido, Hugo Dias Batista, Mario, Guimarães, Jaqueline, Guizeline, João, Hoffmann, Suzana, M Lobo, Francisco Ricardo Lobo, Vinícius, Nascimento, Katia, Nishiyama, Lucas, Pazetto, Daniela, Souza, Rodrigo Souza Rodrigues, Ana Maria Vilela Dos Santos, Jaquelline, Jardim, Joao, Silva, Paulo do Nascimento Junior, Thalissa Hermínia Baio, Gabriel Isaac Pereira de Castro, Henri Roger Watanabe Oliveira, Cristina Prata Amendola, Gutemberg, Cardoso, Daniela, Ortega, Ana Flavia Brotto, Mirella Cristine De Oliveira, Álvaro, Réa-Neto, Fernando, Dias, Pedro, Azambuja, Marcos Freitas Knibel, Antonio, Martins, William, Almeida, Calim Neder Neto, Maria Angela Tardelli, Eliana, Caser, Marcio, Machado, Crisitiano, Aguzzoli, Sérgio, Baldisserotto, Fernanda Beck Tabajara, Fernanda, Bettega, La Hore Correa Rodrigues Júnior, Julia de Gasperi, Lais, Faina, Marcos Farias Nolasco, Bruna Ferreira da Costa Fischer, Mariana Fosch de Campos Ferreira, Cristina, Hartmann, 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Woon, Yuan Liang, Abd Hadi, Husni Zaeem, Ahmad Azam, Ummi Azmira, Alias, Abdul Hafiz, Kesut, Saiful Aizar, Lee, Jun May, Ooi, Dar Vin, Sulaiman, Hetty Ayuni, Tengku Lih, Tengku Alini, Veerakumaran, Jeyaganesh, Rojas, Eder, Resendiz, Gerardo Esteban Alvarez, Zapata, Darcy Danitza Mari, Aguilar López, Julio Cesar Jesú, Flores, Armando Adolfo Alvarez, Amador, Juan Carlosc Bravo, Avila, Erendira Jocelin Dominguez, Aquino, Laura Patricia González, Rodriguez, Ricardo Lopez, Landa, Mariana Torre, Urias, Emma, Hollmann, Marku, Hulst, Abraham, Kirzner, Osne, Preckel, Benedikt, Koopman-van Gemert, Ankie, Buise, Marc, Tolenaar, Noortje, Weber, Eric, de Fretes, Jennifer, Houweling, Peter, Ormskerk, Patricia, Van Bommel, Jasper, Lance, Marcu, Smit-Fun, Valerie, van Zundert, Tom, Baas, Peter, de Boer, Hans Donald, Sprakel, Joost, Elferink-Vonk, Renske, Noordzij, Peter, van Zeggeren, Laura, Brand, Bastiaan, spanjersberg, Rob, ten Bokkel-Andela, Janneke, Numan, Janneke, van Klei, Wilton, van Zaane, 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Tsiligiannis, Sophia, Peat, William, Stephenson, Lorraine, Bradburn, Mike, Pick, Sara, Cunha, Pedro, Olagbaiye, Olufemi, Tayeh, Salim, Abernethy, Caroline, Balasubramaniam, Madhu, Bennett, Rachael, Bolton, David, Martinson, Victoria, Naylor, Charde, Bell, Stephanie, Heather, Blaylock, Kushakovsky, Vlad, Alcock, Liam, Alexander, Hazel, Anderson, Colette, Baker, Paul, Brookes, Morag, Cawthorn, Louise, Cirstea, Emanuel, Colling, Kerry, Coulter, Ian, Das, Suparna, Haigh, Kathryn, Hamdan, Alhafidz, Hugill, Keith, Kottam, Lucksy, Lisseter, Emily, Mawdsley, Matthew, McGivern, Julie, Padala, Krishnaveni, Phelps, Victoria, kumar, Vineshykaa Ramesh, Stewart, Kirsten, Towse, Kayley, Tregonning, Julie, Vahedi, Ali, Walker, Alycon, Baines, Duncan, Bilolikar, Anjali, Chande, Shiv, Copley, Edward, Dunk, Nigel, Kulkarni, Raghavendra, Kumar, Pawan, Metodiev, Yavor, Ncomanzi, Dumisani, Raithatha, Bhavesh, Raymode, Parizade, Szafranski, Jan, Twohey, Linda, Watt, Philip, Weatherall, Lucie, Weatherill, J., Whitman, Zoe, Wighton, Elinor, Abayasinghe, Chamika, Chan, Alexander, Darwish, Sharif, Gill, Jame, Glasgow, Emma, Hadfield, Daniel, Harris, Clair, Kochhar, Arun, Mellis, Clare, Pool, Andrew, Riozzi, Paul, Selman, Andrew, Smith, Emma-Jane, Vele, Liana, Gercek, Yuksel, Guy, Kramer, Holden, Dougla, Watson, Nichola, Whysall, Karen, Andreou, Prematie, Hales, Dawn, Thompson, Jonathan, Bowrey, Sarah, McDonald, Shara, Gilmore, Jemma, Hills, Vicky, Kelly, Chan, Kelly, Sinead, Lloyd, Geraint, Abbott, Tom, Gall, Lewi, Torrance, Hew, Vivian, Mark, Berntsen, Emer, Nolan, Tracey, Turner, Angu, Vohra, Akbar, Brown, Andrew, Clark, Richard, Coughlan, Elaine, Daniel, Conway, Patvardhan, Chinmay, Pearson, Rachel, Predeep, Sheba, Saad, Hesham, Shanmugam, Mohanakrishnan, Varley, Simon, Wylie, Katharine, Cooper, Lucy, Makowski, Arystarch, Misztal, Beata, Moldovan, Eliza, Pegg, Claire, Donovan, Andrew, Foot, Jayne, Large, Simon, Claxton, Andrew, Netke, Bhagyashree, Armstrong, Richard, Calderwood, Claire, Kwok, Andy, Mohr, Otto, Oyeniyi, Peter, Patnaik, Lisa, Post, Benjamin, Ali, Sarah, Arshad, Homa, Baker, Gerard, Brenner, Laura, Brincat, Maximilian, Brunswicker, Annemarie, Cox, Hannah, Cozar, Octavian Ionut, Durst, Alexander, Fengas, Lior, Flatt, Jim, Glister, Georgina, Narwani, Vishal, Photi, Evangelo, Rankin, Adeline, Rosbergen, Melissa, Tan, Mark, Beaton, Ceri, Horn, Rachel, Hunt, Jane, Rousseau, Guy, Stancombe, Lucia, Absar, Mohammed, Allsop, Joanne, Drinkwater, Zoe, Hodgkiss, Tracey, Smith, Kirsty, Brown, Jamie, Alexander-Sefre, Farhad, Campey, Lorraine, Dudgeon, Lucy, Hall, Kathryn, Hitchcock, Rachael, James, Lynne, Smith, Kate, Winstone, Ulrika, Ahmad, Norfaizan, Bauchmuller, Kri, Harrison, Jonathan, Jeffery, Holly, Miller, Duncan, Pinder, Angela, Pothuneedi, Sailaja, Rosser, Jonathan, Sanghera, Sumayer, Swift, Diane, Walker, Rachel, Bester, Delia, Cavanagh, Sarah, Cripps, Heather, Daniel, Harvey, Lynch, Julie, Paton, Alison, Pyke, Shirley, Scholefield, John, Whitworth, Helen, Bottrill, Fiona, Ramalingam, Ganesh, Webb, Stephen, Akerman, Nik, Antill, Philip, Bourner, Lynsey, Buckley, Sarah, Castle, Gail, Charles, Rob, Eggleston, Christopher, Foster, Rebecca, Gill, Satwant, Lindley, Kate, Lklouk, Mohamed, Lowery, Tracey, Martin, Oliver, Milne, David, O’Connor, Patrick, Ratcliffe, Andrew, Rose, Alastair, Smith, Annie, Varma, Sandeep, Ward, Jackie, Barcraft-Barnes, Helena, Camsooksai, Julie, Colvin, Carolyn, Reschreiter, Henrik, Tbaily, Lee, Venner, Nicola, Hamilton, Caroline, Kelly, Lewi, Toth-Tarsoly, Piroska, Dodsworth, Kerry, Foord, Denise, Gordon, Paul, Hawes, Elizabeth, Lamb, Nikki, Mouland, Johanna, Nightingale, Jeremy, Rose, Steve, Schrieber, Joe, Al ‘Amri, Khalid, Aladin, Hafiz, Arshad, Mohammed Asif, Barraclough, Jame, Bentley, Conor, Bergin, Colin, Carrera, Ronald, Clarkson, Aisling, Collins, Michelle, Cooper, Lauren, Denham, Samuel, Griffiths, Ewen, Ip, Peter, Jeyanthan, Somasundaram, Joory, Kavita, Kaur, Satwant, Marriott, Paul, Mitchell, Natalie, Nagaiah, Sukumar, Nilsson, Annette, Parekh, Nilesh, Pope, Martin, Seager, Joseph, Serag, Hosam, Tameem, Alifia, Thomas, Anna, Thunder, Joanne, Torrance, Andrew, Vohra, Ravinder, whitehouse, Arlo, Wong, Tony, Blunt, Mark, Wong, Kate, Giles, Julian, Reed, Isabelle, Weller, Debbie, Bell, Gillian, Birch, Julie, Damant, Rose, Maiden, Jane, Mewies, Clare, Prince, Claire, Radford, Jane, Balain, Birender, Banerjee, Robin, Barnett, Andrew, Burston, Ben, Davies, Kirsty, Edwards, Jayne, Evans, Chri, Ford, David, Gallacher, Pete, Hill, Simon, Jaffray, David, Karlakki, Sudheer, Kelly, Cormac, Kennedy, Julia, Kiely, Nigel, Lewthwaite, Simon, Marquis, Chri, Ockendon, Matthew, Phillips, Stephen, Pickard, Simon, Richardson, Jame, Roach, Richard, Smith, Tony, Spencer-Jones, Richard, Steele, Niall, Steen, Julie, Van Liefland, Marck, White, Steve, Faulds, Matthew, Harris, Meredyth, Kelly, Carrie, Nicol, Scott, Pearson, Sally Anne, Chukkambotla, Srikanth, Andrew, Alyson, Attrill, Elizabeth, Campbell, Graham, Datson, Amanda, Fouracres, Anna, Graterol, Juan, Graves, Lynne, Hong, Bosun, Ishimaru, Alexander, Karthikeyan, Arvind, King, Helen, Lawson, Tom, Lee, Gregory, Lyons, Saoirse, Macalister Hall, Andrew, Mathoulin, Sophie, Mcintyre, Eilidh, Mclaughlin, Danny, Mulcahy, Kathleen, Ratcliffe, Anna, Robbins, Jame, Sung, Weilin, Tayo, Adeoluwa, Trembath, Lisa, Venugopal, Suneetha, Walker, Robert, Wigmore, Geoffrey, Boereboom, Catherine, Downes, Charlotte, Humphries, Ryan, Melbourne, Susan, Smith, Coral, Tou, Samson, Ullah, Shafa, Batchelor, Nick, Boxall, Leigh, Broomby, Rupert, Deen, Tariq, Hellewell, Alistair, Helliwell, Laurence, Hutchings, Melanie, Hutchins, David, Keenan, Samantha, Mackie, Donna, Donna, Alison, Smith, France, Stone, Lucy, Thorpe, Kevin, Wassall, Richard, Woodgate, Andrew, Baillie, Shelley, Campbell, Tara, James, Sarah, King, Chri, Marques de Araujo, Daniela, Martin, Daniel, Morkane, Clare, Neely, Julia, Rajendram, Rajkumar, Burton, Megan, James, Kathryn, Keevil, Edward, Minik, Orsolya, Morgan, Jenna, Musgrave, Anna, Rajanna, Harish, Roberts, Tracey, Adamson, Michael, Jumbe, Sandra, Kendall, Jennie, Muthuswamy, Mohan Babu, Anderson, Charlotte, Cruikshanks, Andrew, Wrench, Ian, Zeidan, Lisa, Ardern, Diane, Harris, Benjamin, Hellstrom, Johanna, Martin, Jane, Thomas, Richard, Varsani, Nimu, Wrey Brown, Caroline, Docherty, Philip, Gillies, Michael, McGregor, Euan, Usher, Helen, Craig, Jayne, Smith, Andrew, Ahmad, Tahania, Bodger, Phoebe, Creary, Thai, Fowler, Alexander, Hewson, Ru, Ijuo, Eke, Jones, Timothy, Kantsedikas, Ilya, Lahiri, Sumitra, McLean, Aaron Lawson, Niebrzegowska, Edyta, Phull, Mandeep, Wang, Difei, Wickboldt, Nadine, Baldwin, Jacqueline, Doyle, Donna, Mcmullan, Sean, Oladapo, Michelle, Owen, Thoma, Williams, Alexandra, Daniel, Hull, Gregory, Peter, Husain, Tauqeer, Kirk-Bayley, Justin, Mathers, Edward, Montague, Laura, White, Stuart, Avis, Joanne, Cook, Tim, Dali-Kemmery, Lola, Kerslake, Ian, Lambourne, Victoria, Pearson, Annabel, 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Knaggs, Alison, Markar, Sheraz, Perera, Anisha, Scott, Alasdair, Shida, Asako, Sirha, Ravneet, Wright, Sally, Frost, Victoria, Gray, Catherine, MacGregor, Mark, Andrews, Emma, Arrandale, Lindsay, Barrett, Stephen, Cifra, Elna, Cooper, Mariese, Dragnea, Drago, Elna, Cifra, Maclean, Jennifer, Meier, Sonja, Milliken, Donald, Munns, Christopher, Ratanshi, Nadir, Salvana, Abegail, Watson, Anthony, Ali, Hani, Campbell, Gill, Critchley, Rebecca, Hicks, Catherine, Liddle, Alison, Pass, Marc, Ritchie, Charlotte, Thomas, Charlotte, Too, Lingxi, Welsh, Sarah, Gill, Talvinder, Johnson, Joanne, Reed, Joanne, Davis, Edward, Papadopoullos, Sam, Attwood, Clare, Biffen, Andrew, Boulton, Kerenza, Gray, Sophie, Hay, David, Mills, Sarah, Montgomery, Jane, Riddell, Rory, Simpson, Jame, Bhardwaj, Neeraj, Paul, Elaine, Uwubamwen, Nosakhare, Alexander, Maini, Arrich, Jame, Arumugam, Swarna, Blackwood, Dougla, Boggiano, Victoria, Brown, Robyn, Lam Chan, Yik, Chatterjee, Devnandan, Chhabra, Ashok, Christian, Rachel, Costelloe, Hannah, Coxwell Matthewman, Madeline, Dalton, Emma, Darko, Julia, Davari, Maria, Dave, Tejal, Deacon, Matthew, Deepak, Shantal, Edmond, Holly, Ellis, Jessica, El-Sayed, Ahmed, Eneje, Philip, English, Rose, Ewe, Renee, Foers, William, Franklin, John, Gallego, Laura, Garrett, Emily, Goldberg, Olivia, Goss, Harry, Greaves, Rosanna, Harris, Rudy, Hennings, Charle, Jones, Eleanor, Kamali, Nelson, Kokkinos, Naomi, Lewis, Cary, Lignos, Leda, Malgapo, Evaleen Victoria, Malik, Rizwana, Milne, Andrew, Mulligan, John-Patrick, Nicklin, Philippa, Palipane, Natasha, Parsons, Thoma, Piper, Rebecca, Prakash, Rohan, Ramesh, Byron, Rasip, Sarah, Reading, Jacob, Rela, Mariam, Reyes, Anna, Robert, Stephen, Rooms, Martin, Shah, Karishma, Simons, Henry, Solanki, Shalil, Spowart, Emma, Stevens, Amy, Thomas, Christopher, Waggett, Helena, Yassaee, Arrash, Kennedy, Anthony, Scott, Sara, Somanath, Sameer, Berg, Andrew, Hernandez, Miguel, Nanda, Rajesh, Tank, Ghanshyambhai, Wilson, Natalie, 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Kumara, P., Simeson, K., Yarwood, J., Browning, J., Hatton, J., Julian, H., Mitra, A., Newton, M., Pernu, P., Wilson, A., Commey, T., Foot, H., Glover, L., Gupta, A., Lancaster, N., Levin, J., Mackenzie, F., Mestanza, C., Nofal, E., Pout, L., Varden, R., Wild, J., Jones, S., Moreton, S., Pulletz, M., Davies, C., Martin, M., Thomas, S., Burns, K., McArthur, C., Patel, P., Lau, G., Rich, N., Davis, F., Lyons, R., Port, B., Prout, R., Smith, C., Adelaja, Y., Bennett, V., Bidd, H., Dumitrescu, A., Murphy, J.F., Keen, A., Mguni, N., Ong, C., Adams, G., Boshier, P., Brown, R., Butryn, I., Chatterjee, J., Freethy, A., Lockwood, G., Tsakok, M., Tsiligiannis, S., Peat, W., Stephenson, L., Bradburn, M., Pick, S., Cunha, P., Olagbaiye, O., Tayeh, S., Abernethy, C., Balasubramaniam, M., Bennett, R., Bolton, D., Martinson, V., Bell, S., Heather, B., Kushakovsky, V., Alcock, L., Alexander, H., Anderson, C., Baker, P., Brookes, M., Cawthorn, L., Cirstea, E., Colling, K., Coulter, I., Das, S., Haigh, K., Hamdan, A., Hugill, K., Kottam, L., Lisseter, E., Mawdsley, M., McGivern, J., Padala, K., Phelps, V., Kumar, V.R., Stewart, K., Towse, K., Tregonning, J., Vahedi, A., Walker, A., Baines, D., Bilolikar, A., Chande, S., Copley, E., Dunk, N., Kulkarni, R., Kumar, P., Metodiev, Y., Ncomanzi, D., Raithatha, B., Raymode, P., Szafranski, J., Twohey, L., Watt, P., Weatherall, L., Whitman, Z., Wighton, E., Abayasinghe, C., Chan, A., Darwish, S., Gill, J., Glasgow, E., Hadfield, D., Harris, C., Kochhar, A., Mellis, C., Pool, A., Riozzi, P., Selman, A., Smith, E.J., Vele, L., Gercek, Y., Guy, K., Holden, D., Watson, N., Whysall, K., Andreou, P., Hales, D., Thompson, J., Bowrey, S., McDonald, S., Gilmore, J., Hills, V., Kelly, C., Kelly, S., Lloyd, G., Abbott, T., Gall, L., Torrance, H., Vivian, M., Berntsen, E., Nolan, T., Turner, A., Vohra, A., Brown, A., Clark, R., Coughlan, E., Daniel, C., Patvardhan, C., Pearson, R., Predeep, S., Saad, H., Shanmugam, M., Varley, S., Wylie, K., Cooper, L., Makowski, A., Misztal, B., Moldovan, E., Pegg, C., Donovan, A., Foot, J., Large, S., Claxton, A., Netke, B., Armstrong, R., Calderwood, C., Kwok, A., Mohr, O., Oyeniyi, P., Patnaik, L., Post, B., Ali, S., Arshad, H., Baker, G., Brenner, L., Brincat, M., Brunswicker, A., Cox, H., Cozar, O.I., Durst, A., Fengas, L., Flatt, J., Glister, G., Narwani, V., Photi, E., Rankin, A., Rosbergen, M., Beaton, C., Horn, R., Hunt, J., Rousseau, G., Stancombe, L., Absar, M., Allsop, J., Drinkwater, Z., Hodgkiss, T., Smith, K., Alexander-Sefre, F., Campey, L., Dudgeon, L., Hall, K., Hitchcock, R., James, L., Winstone, U., Ahmad, N., Bauchmuller, K., Harrison, J., Jeffery, H., Miller, D., Pinder, A., Pothuneedi, S., Rosser, J., Sanghera, S., Swift, D., Walker, R., Bester, D., Cavanagh, S., Cripps, H., Daniel, H., Lynch, J., Pyke, S., Scholefield, J., Whitworth, H., Bottrill, F., Ramalingam, G., Webb, S., Akerman, N., Antill, P., Bourner, L., Buckley, S., Castle, G., Charles, R., Eggleston, C., Foster, R., Gill, S., Lindley, K., Lklouk, M., Lowery, T., Martin, O., Milne, D., O'Connor, P., Ratcliffe, A., Rose, A., Smith, A., Varma, S., Ward, J., Barcraft-Barnes, H., Camsooksai, J., Colvin, C., Reschreiter, H., Tbaily, L., Venner, N., Hamilton, C., Kelly, L., Toth-Tarsoly, P., Dodsworth, K., Foord, D., Gordon, P., Hawes, E., Lamb, N., Mouland, J., Nightingale, J., Rose, S., Schrieber, J., Al 'Amri, K., Aladin, H., Arshad, M.A., Barraclough, J., Bentley, C., Bergin, C., Carrera, R., Clarkson, A., Collins, M., Denham, S., Griffiths, E., Ip, P., Jeyanthan, S., Joory, K., Kaur, S., Marriott, P., Mitchell, N., Nagaiah, S., Nilsson, A., Parekh, N., Pope, M., Seager, J., Serag, H., Tameem, A., Thomas, A., Thunder, J., Torrance, A., Vohra, R., Whitehouse, A., Wong, T., Blunt, M., Wong, K., Giles, J., Reed, I., Weller, D., Bell, G., Birch, J., Damant, R., Maiden, J., Mewies, C., Prince, C., Radford, J., Balain, B., Banerjee, R., Barnett, A., Burston, B., Edwards, J., Evans, C., Ford, D., Gallacher, P., Hill, S., Jaffray, D., Karlakki, S., Kennedy, J., Kiely, N., Lewthwaite, S., Marquis, C., Ockendon, M., Phillips, S., Pickard, S., Richardson, J., Roach, R., Smith, T., Spencer-Jones, R., Steele, N., Steen, J., Van Liefland, M., White, S., Faulds, M., Harris, M., Nicol, S., Pearson, S.A., Chukkambotla, S., Andrew, A., Attrill, E., Campbell, G., Datson, A., Fouracres, A., Graterol, J., Graves, L., Hong, B., Ishimaru, A., Karthikeyan, A., King, H., Lawson, T., Lee, G., Lyons, S., Macalister Hall, A., Mathoulin, S., Mcintyre, E., Mclaughlin, D., Mulcahy, K., Robbins, J., Sung, W., Tayo, A., Trembath, L., Venugopal, S., Wigmore, G., Boereboom, C., Downes, C., Humphries, R., Melbourne, S., Tou, S., Ullah, S., Batchelor, N., Boxall, L., Broomby, R., Deen, T., Hellewell, A., Helliwell, L., Hutchings, M., Hutchins, D., Keenan, S., Mackie, D., Donna, A., Smith, F., Stone, L., Thorpe, K., Wassall, R., Woodgate, A., Baillie, S., Campbell, T., James, S., King, C., Marques de Araujo, D., Martin, D., Morkane, C., Neely, J., Rajendram, R., Burton, M., James, K., Keevil, E., Minik, O., Morgan, J., Musgrave, A., Rajanna, H., Roberts, T., Adamson, M., Jumbe, S., Kendall, J., Muthuswamy, M.B., Cruikshanks, A., Wrench, I., Zeidan, L., Ardern, D., Harris, B., Hellstrom, J., Martin, J., Thomas, R., Varsani, N., Wrey Brown, C., Docherty, P., Gillies, M., McGregor, E., Usher, H., Craig, J., Ahmad, T., Bodger, P., Creary, T., Fowler, A., Ijuo, E., Jones, T., Kantsedikas, I., Lahiri, S., McLean, A.L., Niebrzegowska, E., Phull, M., Wickboldt, N., Baldwin, J., Doyle, D., Mcmullan, S., Oladapo, M., Owen, T., Williams, A., Gregory, P., Husain, T., Kirk-Bayley, J., Mathers, E., Montague, L., Avis, J., Cook, T., Dali-Kemmery, L., Kerslake, I., Lambourne, V., Pearson, A., Boyd, C., Callaghan, M., Lawson, C., McCrossan, R., Nesbitt, V., O'connor, L., Sinclair, R., Farid, N., Morgese, C., Bhatia, K., Karmarkar, S., Ahmed, J., Branagan, G., Hutton, M., Swain, A., Brookes, J., Cornell, J., Dolan, R., Hulme, J., Jansen van Vuuren, A., Jowitt, T., Kalashetty, G., Lloyd, F., Patel, K., Sherwood, N., Brown, L., Chandler, B., Deighton, K., Emma, T., Haunch, K., Cheeseman, M., Dent, K., Gray, C., Hood, M., Jones, D., Juj, J., Rao, R., Walker, T., Al Anizi, M., Cheah, C., Cheing, Y., Coutinho, F., Gondo, P., Hadebe, B., Onie Hove, M., Khader, A., Krishnachetty, B., Rhodes, K., Sokhi, J., Baker, K.A., Bertram, W., Looseley, A., Mouton, R., Arnold, G., Arya, S., Balfoussia, D., Baxter, L., Harris, J., Jones, C., Knaggs, A., Markar, S., Perera, A., Scott, A., Shida, A., Sirha, R., Wright, S., Frost, V., MacGregor, M., Andrews, E., Arrandale, L., Barrett, S., Cifra, E., Cooper, M., Dragnea, D., Elna, C., Maclean, J., Meier, S., Milliken, D., Munns, C., Ratanshi, N., Salvana, A., Watson, A., Ali, H., Critchley, R., Hicks, C., Liddle, A., Pass, M., Ritchie, C., Thomas, C., Too, L., Welsh, S., Gill, T., Johnson, J., Reed, J., Davis, E., Papadopoullos, S., Attwood, C., Biffen, A., Boulton, K., Gray, S., Hay, D., Mills, S., Montgomery, J., Riddell, R., Simpson, J., Bhardwaj, N., Paul, E., Uwubamwen, N., Alexander, M., Arrich, J., Arumugam, S., Blackwood, D., Boggiano, V., Lam Chan, Y., Chatterjee, D., Chhabra, A., Christian, R., Costelloe, H., Coxwell Matthewman, M., Dalton, E., Darko, J., Davari, M., Dave, T., Deacon, M., Deepak, S., Edmond, H., Ellis, J., El-Sayed, A., Eneje, P., English, R., Ewe, R., Foers, W., Franklin, J., Gallego, L., Garrett, E., Goldberg, O., Goss, H., Greaves, R., Harris, R., Hennings, C., Jones, E., Kamali, N., Kokkinos, N., Lewis, C., Lignos, L., Malgapo, E.V., Malik, R., Milne, A., Mulligan, J.P., Nicklin, P., Palipane, N., Parsons, T., Piper, R., Prakash, R., Ramesh, B., Rasip, S., Reading, J., Rela, M., Reyes, A., Robert, S., Rooms, M., Shah, K., Simons, H., Solanki, S., Spowart, E., Stevens, A., Waggett, H., Yassaee, A., Kennedy, A., Scott, S., Somanath, S., Berg, A., Hernandez, M., Nanda, R., Tank, G., Wilson, N., Wilson, D., Al-Soudaine, Y., Baldwin, M., Cornish, J., Davies, Z., Davies, L., Edwards, M., Frewer, N., Gallard, S., Glasbey, J., Harries, R., Hopkins, L., Kim, T., Koompirochana, V., Lawson, S., Lewis, M., Makzal, Z., Scourfield, S., Ahmad, Y., Bates, S., Blackwell, C., Bryant, H., Coulter, S., Cruickshank, R., Daniel, S., Daubeny, T., Golder, K., Hawkins, L., Helen, B., Hinxman, H., Levett, D., Skinner, B., Walsgrove, J., Dickson, J., Constantin, K., Karen, M., O'Brien, P., O'Donohoe, L., Payne, H., Sundayi, S., Walker, E., Brooke, J., Cardy, J., Humphreys, S., Kessack, L., Kubitzek, C., Kumar, S., Cotterill, D., Hodzovic, E., Hosdurga, G., Miles, E., Saunders, G., Campbell, M., Chan, P., Jemmett, K., Raj, A., Naik, A., Ramamoorthy, R., Shah, N., Sylvan, A., Blyth, K., Burtenshaw, A., Freeman, D., Johnson, E., Lo, P., Martin, T., Plunkett, E., Wollaston, J., Allison, J., Carroll, C., Craw, N., Craw, S., Pitt-Kerby, T., Rowland-Axe, R., Spurdle, K., McDonald, A., Simon, D., Sinha, V., Banner-Goodspeed, V., Boone, M., Campbell, K., Lu, F., Scannell, J., Sobol, J., Balajonda, N., Clemmons, K., Conde, C., Funk, B., Hopkins, T., Olaleye, O., Omer, O., Pender, M., Porto, A., Waweru, P., Yeh, E., Bodansky, D., Evans, A., Kleopoulos, S., Maril, R., Mathney, E., Sanchez, A., Tinuoye, E., Bateman, B., Eng, K., Jiang, N., Ladha, K., Needleman, J., Chen, L.L., Lane, R., Robinowitz, D., Ghushe, N., Irshad, M., Patel, S., Takemoto, S., Wallace, A., Mazzeffi, M., Rock, P., Wallace, K., Zhu, X., Chua, P., Mattera, M., Sharar, R., Thilen, S., Treggiari, M., Morgan, A., Sofjan, I., Subramaniam, K., Avidan, M., Maybrier, H., Muench, M., and Wildes, T.
Subjects: Male, HSJ UCI, Critical Care and Intensive Care Medicine, law.invention, Perioperative Care/methods, 0302 clinical medicine, Surgical procedures, 030202 anesthesiology, law, Critical care/utilisation, Postoperative care/methods, Postoperative care/statistics and numerical data, Surgical procedures, operative/mortality, statistics and numerical data, Prospective Studies, Postoperative Period, Postoperative care/methods, education.field_of_study, Postoperative care/method, Elective Surgical Procedures/mortality, fluid output, Middle Aged, fluid administration, Intensive care unit, Hospitalization, Length of Stay/statistics & numerical data, operative/mortality, Intensive Care Units/statistics & numerical data, outcome, Female, Elective Surgical Procedure, Human, Adult, medicine.medical_specialty, Logistic Model, Postoperative care/statistics and numerical data, Critical care/utilisation, Population, Intensive Care Unit, Elective Surgical Procedures/statistics & numerical data, Hospitalization/statistics & numerical data, Humans, Logistic Models, Surgical procedures, operative/mortality, Postoperative care, methods, Perioperative Care, NO, 03 medical and health sciences, Anesthesiology, Intensive care, medicine, Elective surgery, Intensive care medicine, education, business.industry, 030208 emergency & critical care medicine, Perioperative, Length of Stay, Clinical trial, Prospective Studie, septic shock, business
Abstract: PURPOSE: As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality. METHODS: Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests. RESULTS: 44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10-5.21]; p < 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings. CONCLUSIONS: We did not identify any survival benefit from critical care admission following surgery. info:eu-repo/semantics/publishedVersion
Published: 2017
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47. Impacts of omission of breast cancer surgery in older women with ER+ early breast cancer. A risk stratified analysis of survival and quality of life outcomes

Author: Sue Ward, Lynda Wyld, Maria Burton, Riccardo A. Audisio, T. Robinson, Adrian Edwards, Stephen J Walters, Tim Chater, Jenna Morgan, Charlene Martin, Geoffrey Holmes, Kirsty Pemberton, Malcolm Wr. Reed, Karen Collins, Annaliza Todd, K.L. Cheung, A. Ring, and Mike Bradburn
Subjects: Stratified analysis, Oncology, Cancer Research, medicine.medical_specialty, Breast cancer, Quality of life, business.industry, Internal medicine, medicine, business, medicine.disease, Early breast cancer
Published: 2020
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48. 190P Impact of chemotherapy for early stage breast cancer on quality of life in older adults: Results from 2811 women enrolled in the Bridging the Age Gap study

Author: Alistair Ring, Lynda Wyld, Jenna Morgan, Nicolò Matteo Luca Battisti, Mike Bradburn, and Esther Herbert
Subjects: Chemotherapy, Pediatrics, medicine.medical_specialty, Bridging (networking), business.industry, medicine.medical_treatment, Hematology, medicine.disease, Breast cancer, Oncology, Quality of life, medicine, Stage (cooking), business
Published: 2020
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49. Implementation of the BRESO Theoretical and practical knowledge curriculum for European Breast Surgeons: The time has come

Author: Wiebke Wandschneider, Alessio Vinci, Antonio Esgueva, Veli Vural, Jenna Morgan, Giacomo Montagna, Nicola Rocco, R. Di Micco, and Giovanni Corso
Subjects: Surgeons, medicine.medical_specialty, business.industry, Breast surgeons, General Medicine, medicine.disease, Breast cancer, Oncology, Humans, Medicine, Surgery, Medical physics, Curriculum, business
Published: 2020
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50. Bridging the Age Gap in Breast Cancer - Analysis of the Complication Rates of Surgery in Older Women

Author: Jayan George, Jenna Morgan, Charlene Martin, Anne Shrestha, Ward Sue, Geoff Holmes, Mike Bradburn, Maria Burton, Tim Chater, Kirsty Pemberton, Anthony Nettleship, Stephen Walters, Alistair Ring, Thomson Robinson, Kwok Leung Cheung, Riccardo Audisio, Malcolm Reed, Lynda Wyld, and null Bridging the Age Gap Trial Management Group
Subjects: education.field_of_study, medicine.medical_specialty, business.industry, medicine.medical_treatment, Mortality rate, Population, Retrospective cohort study, General Medicine, medicine.disease, Surgery, Breast cancer, Oncology, Seroma, medicine, Breast-conserving surgery, education, business, Adverse effect, Mastectomy
Abstract: Background: The Bridging the Age Gap in Breast Cancer study is a multicentre retrospective cohort study examining the management of older patients with breast cancer. This study aimed to examine the selection criteria for breast cancer surgery in patients over 70 and the adverse events risk in this population. We present the adverse event risks for breast cancer surgery in women over age 70 in the UK according to surgical type. Materials and Methods: Baseline information on patient characteristics, surgery type and adverse events was collected across 56 UK breast units. Surgery was classified as major (mastectomy or axillary node clearance) or minor surgery (breast conserving surgery +/- sentinel node biopsy). Adverse events were recorded for 2 years following surgery and classified using the Common Terminology for Classification of Adverse Events system and designated as systemic or local/wound complications. Rates of adverse events were calculated and compared between surgical categories using Chi Squared. Results: Between 2013-2018, 3460 women with operable breast cancer were recruited; 2792 (80.7%) were treated surgically. There were 62 bilateral tumours, giving a total of 2854 surgical events (1321 major, 1533 minor). There were no surgical related deaths (30-day mortality). The overall rate of systemic complications was 59/2854 (2.1%) and local complications was 1072/2854 (37.6%) although 547 had only a seroma and these have been excluded from further analysis. Major surgery was associated with higher rates of local complications (22.7%) vs minor (14.7%; P
Published: 2020
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