Imperial College Healthcare NHS Trust Research Articles

Anaphylaxis to intravenous gelatin-based solutions: a case series examining clinical features and severity.

The proportion of patients receiving intravenous gelatin-based colloids has increased in the last decade due to safety concerns about starch-based products. Recent research suggests hypersensitivity reactions to intravenous gelatin-based solutions occur at similar rates per administration as non-depolarising neuromuscular blocking agents such as rocuronium (6.2/100,000 administrations). There are scant published data on clinical features, diagnosis and time course of these reactions. We undertook a review of cases reported and tested at one of the UK's largest drug allergy clinics. All patients seen in the drug allergy clinic at Imperial College Healthcare NHS Trust (London, UK) with a confirmed diagnosis of anaphylaxis to gelatin-based solutions between May 2013 and May 2018 were included. We retrospectively reviewed clinical histories, skin test results and severity of reactions in this cohort of patients. Twelve patients with anaphylaxis to gelatin-based solutions were identified (eight women, mean (SD) age 58 (17) years). Eleven reactions were severe or life-threatening with three progressing to cardiac arrest. Presentation was commonly delayed; only three patients suffered reactions within 5min of the solution being administered with a further six presenting 10-70min later. Where measured, tryptase was elevated in all patients (median (IQR [range]) 14.7 (8.2-23.8 [6.5-83.4]) ng.ml-1 ). Reactions to gelatin-based solutions are usually severe and can present with latency uncommon with other intravenous anaesthetic triggers. The use of gelatin-based solutions in the peri-operative setting should be re-assessed given the risk of severe allergy.

An audit of 200 electronic requests for computed tomography pulmonary angiograms (CTPAs) at Imperial College Healthcare NHS Trust

Category: Respiratory

Clinical and biochemical characteristics of patients presenting with pituitary apoplexy.

PurposeTo review the clinical and biochemical characteristics and clinical outcome of patients presenting with pituitary apoplexy to a tertiary centre.MethodsWe retrospectively reviewed the clinical features, predisposing factors, biochemistry and clinical outcome of patients presenting with pituitary apoplexy to Imperial College Healthcare NHS Trust between 1991 and 2015.ResultsWe identified 64 patients with pituitary apoplexy (more complete clinical records were available in 52 patients). The median age at presentation was 46.7 years (IQR 31.5–57.0 years). Pituitary apoplexy was the first presentation of pituitary disease in 38/52 of patients and predisposing factors were identified in 28/52. Pituitary apoplexy predominantly occurred in patients with non-functioning pituitary adenomas (47/52). Headache was most commonly described as sudden onset, severe, lateralising to the frontal or temporal regions. Symptoms of meningeal irritation were reported in 7/18 and visual abnormalities in 22/35. A pre-treatment serum cortisol <100 nmol/L was recorded in 12/31 of patients. All patients with visual disturbance had some resolution of their visual symptoms whether managed surgically (14/14) or conservatively (5/5), although pituitary endocrine function did not fully recover in any patient.ConclusionsIn conclusion, these data describe the clinical features of pituitary apoplexy to aid the clinician in diagnosing this rare emergency presentation of pituitary disease. Prospective multicentre studies of the presentation of pituitary apoplexy are required to further characterise presentation and outcomes.

PO-357 SREBP1 drives cell-autonomous cytoskeletal changes by KRT80 remodelling during ERα breast cancer progression

IntroductionApproximately 30% of oestrogen receptor α positive (ERα) breast cancer patients progress to invasive metastatic disease despite adjuvant treatment with targeted endocrine therapies. The relationship between acquisition of drug resistance and invasive potential is poorly understood. Currently, invasive behaviour is thought to be driven mainly by epithelial to mesenchymal transition.Material and methodsMCF7 cell line and derived resistant clones were used for this study. MCF7 Tamoxifen Resistant (MCF7TR) and LTED (Long Term Oestrogen Deprivation) were derived from MCF7 upon one-year Tamoxifen or oestrogen deprivation, respectively. LTED combination treatments were also used (LTEDT and LTEDF). Additionally, we used T47D and T47D-LTED. Stable cell lines were generated for both KRT80 over-expression and knockdown. 3D organoids invasion assay, immunofluorescence, confocal microscopy, RNA-seq, ChIP-seq, RT-qPCR and Western blot were performed. Seventy-five human breast specimens and ten metastatic lymph nodes were selected with the approval of Imperial College Healthcare NHS Trust Tissue Bank. Twenty women with suspected breast cancer were prospectively recruited and radiological exam using shear wave ultrasound was used to determine tissue stiffness in the normal and peri-tumoral stroma, and suspected lesion.Results and discussionsIn this study, we show that cells that acquire resistance to aromatase inhibitors (AI) undergo active cytoskeleton re-organisation via Keratin 80 (KRT80) and F-Actin remodelling. These features directly drive the invasive phenotype. Mechanistically, we show that this process is driven by epigenetic reprogramming at the type II keratin locus (chromosome 12) leading to Keratin 80 (KRT80) up-regulation. Reprogramming is dependent on de novo SREBP1 binding to a single enhancer that is activated upon chronic AI treatment. AI-treated patients show KRT80 cytoskeletal re-organisation and an increased number of KRT80 positive cells at relapse. We find that KRT80 activation and redeployment leads to increased F-actin deposition and focal adhesion. Additionally, we show that KRT80 manipulation directly contributes to changes in cellular stiffness and invasive potential. In agreement, shear-wave elasticity imaging of prospective patients show that KRT80 levels correlate with stiffer tumours in vivo.ConclusionCollectively, our data uncover an unexpected and potentially targetable link between epigenetic reprogramming and cytoskeletal changes promoting cell invasion.

Development of a patient-centred intervention to improve knowledge and understanding of antibiotic therapy in secondary care

BackgroundWe developed a personalised antimicrobial information module co-designed with patients. This study aimed to evaluate the potential impact of this patient-centred intervention on short-term knowledge and understanding of antimicrobial therapy in secondary care.MethodsThirty previous patients who had received antibiotics in hospital within 12 months were recruited to co-design an intervention to promote patient engagement with infection management. Two workshops, containing five focus-groups were held. These were audio-recorded. Data were analysed using a thematic framework developed deductively based on previous work. Line-by-line coding was performed with new themes added to the framework by two researchers. This was used to inform the development of a patient information module, embedded within an electronic decision support tool (CDSS).The intervention was piloted over a four-week period at Imperial College Healthcare NHS Trust on 30 in-patients. Pre- and post-intervention questionnaires were developed and implemented to assess short term changes in patient knowledge and understanding and provide feedback on the intervention. Data were analysed using SPSS and NVIVO software.ResultsWithin the workshops, there was consistency in identified themes. The participants agreed upon and co-designed a personalised PDF document that could be integrated into an electronic CDSS to be used by healthcare professionals at the point-of-care. Their aim for the tool was to provide individualised practical information, signpost to reputable information sources, and enhance communication between patients and healthcare professionals.Eighteen out of thirty in-patients consented to participant in the pilot evaluation with 15/18(83%) completing the study. Median (range) age was 66(22–85) years. The majority were male (10/15;66%). Pre-intervention, patients reported desiring further information regarding their infections and antibiotic therapy, including side effects of treatment. Deployment of the intervention improved short term knowledge and understanding of individuals infections and antibiotic management with median (IQR) scores improving from 3(2–5)/13 to 10(6–11)/13. 13/15(87%) reported that they would use the intervention again.ConclusionA personalised, patient-centred intervention improved understanding and short-term knowledge of infections and antibiotic therapy in participating patients’. Long term impact on attitudes and behaviours post discharge will be further investigated.

Evaluation of parental experience post-discharge and development of a parent focus group

The aim of the Integrated Family Delivered Neonatal Care (IFDC) project is to improve parent-experience, parent-infant bonding, parental mental health, and infant health outcomes by pioneering a new care model at Imperial College Healthcare NHS Trust based on international evidence. It is particularly challenging to measure parent experience in neonatology, and there isn't a uniform internationally accepted tool for this. Understanding parents' experiences is vital to understand how quality of care can be improved. As parents are in a very vulnerable situation in the neonatal unit progressing on an often long, unpredictable and complicated journey, special approach and tools are needed to distill their overwhelming experience.Within the expanse of the Quality Improvement project we hoped to focus and achieve the following objectives:1.To develop a sustainable feedback model for parent experience to collect feedback on neonatal care using validated tools.2.To establish a parent focus group to collect feedback about our care and to create an experience co-designed parent educational material for our project.

Correction to: IRIS study: a phase II study of the steroid sulfatase inhibitor Irosustat when added to an aromatase inhibitor in ER-positive breast cancer patients.

In the original publication of the article, a part of acknowledgement section was missed out. The omitted acknowledgement is given below: 'The study was coordinated by the Imperial Clinical Trials Unit-Cancer, Imperial College London and Sponsored by Imperial College London. The Imperial Clinical Trials Unit receives funding from the National Institute for Health (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This study was supported by Imperial Experimental Cancer Medicine Centre and Cancer Research UK Imperial Centre'.

Corrigendum: Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.

HRW, CPC, MR, MRB, PBM, MB and MJC were funded by the National Institutes for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts and The London School of Medicine and Dentistry. HG was funded by the NIHR Imperial College Health Care NHS Trust and Imperial College London Biomedical Research Centre. MR was a recipient from China Scholarship Council (No. 2011632047). BM holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship, funded from award MR/L016311/1. JMMH was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834), European Commission Framework Programme 7 (HEALTH-F2-2012-279233). BK holds a British Heart Foundation Personal Chair (CH/13/2/30154). NJS holds a chair funded by the British Heart Foundation and is a NIHR Senior Investigator. FD was funded by the MRC Unit at the University of Bristol (MC_UU_12013/1-9). PSu was funded by the UK Medical Research Council (G0800270). CL and AK were funded by the NHLBI intramural funding. CNC was funded by the National Institutes of Health (HL113933, HL124262). PVDH was funded by the ZonMw grant 90.700.441, Marie Sklodowska-Curie GF (call: H2020- MSCA-IF-2014, Project ID: 661395). NV was supported by Marie Sklodowska-Curie GF grant (661395) and ICIN-NHI. NP received funding from the UK National Institute for Health Research Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London and also from his Senior Investigator Award. PS was supported by the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London. ST was supported by the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London. PFO received funding from the UK Medical Research Council (MR/N015746/1) and the Wellcome Trust (109863/Z/15/Z). IK was supported by the EU PhenoMeNal project (Horizon 2020, 654241). AC was funded by the National Institutes of Health (HL128782, HL086694). MF was supported by the Wellcome Trust core award (090532/Z/09/Z) and the BHF Centre of Research Excellence, Oxford (RE/13/1/30181). CH was funded by an MRC core grant for QTL in Health and Disease programme. Some of this work used the ALICE and SPECTRE High Performance Computing Facilities at the University of Leicester. MJC is a National Institute for Health Research (NIHR) senior investigator. PE is a National Institute for Health Research (NIHR) senior investigator and acknowledges support from the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London, and the NIHR Health Protection Research Unit in Health Impact of Environmental Hazards (HPRU-2012-10141). As director of the MRC-PHE Centre for Environment and Health, PE acknowledges support from the Medical Research Council and Public Health England (MR/L01341X/1). This work used the computing resources of the UK MEDical BIOinformatics partnership - aggregation, integration, visualisation and analysis of large, complex data (UK MED-BIO) which is supported by the Medical Research Council (MR/L01632X/1). This research was supported by the British Heart Foundation (grant SP/13/2/30111). Project title: Large-scale comprehensive genotyping of UK Biobank for cardiometabolic traits and diseases: UK CardioMetabolic Consortium (UKCMC).

Prednisolone has the same cardiovascular risk profile as hydrocortisone in glucocorticoid replacement.

IntroductionPatients who need glucocorticoid replacement in both primary and secondary adrenal insufficiency (AI) have the choice of either once-daily prednisolone or thrice-daily hydrocortisone. A recent European study found no difference between prednisolone and hydrocortisone users in several markers including glucose, weight, body mass index, systolic and diastolic blood pressure and waist circumference, although an increase in cholesterol and low-density lipoprotein (LDL) was suggested in a subgroup of these patients. The aim of this study was to expand the evidence base for the use of these agents as replacement therapy.MethodsData from 82 patients on hydrocortisone and 64 patients on prednisolone for AI at Imperial College Healthcare NHS Trust were analysed.ResultsThere was no significant difference in total cholesterol, LDL levels or any other risk factors between hydrocortisone and prednisolone patients. Prednisolone was subjectively significantly more convenient than hydrocortisone (P = 0.048).ConclusionsPrednisolone once daily is more convenient than hydrocortisone thrice daily, and there is no difference in the markers of cardiovascular risk measured. Because prednisolone mimics the circadian rhythm better than other glucocorticoids, it should be considered as an alternative to hydrocortisone for AI.

Transition to consultant: a critical career point.

Medical EducationVolume 51, Issue 11 p. 1182-1183 Really Good Stuff: Lessons learned through innovation in medical education Transition to consultant: a critical career point Camilla Sen, Camilla SenSearch for more papers by this authorHermione Race, Hermione RaceSearch for more papers by this authorCaroline Scott-Lang, Corresponding Author Caroline Scott-Lang caroline.scott-lang@nhs.net Correspondence: Caroline Scott-Lang, St. Mary's Hospital, Imperial College Healthcare NHS Trust, Praed Street, London W2 1NY. 020 3312 6666; E-mail: caroline.scott-lang@nhs.netSearch for more papers by this author Camilla Sen, Camilla SenSearch for more papers by this authorHermione Race, Hermione RaceSearch for more papers by this authorCaroline Scott-Lang, Corresponding Author Caroline Scott-Lang caroline.scott-lang@nhs.net Correspondence: Caroline Scott-Lang, St. Mary's Hospital, Imperial College Healthcare NHS Trust, Praed Street, London W2 1NY. 020 3312 6666; E-mail: caroline.scott-lang@nhs.netSearch for more papers by this author First published: 12 September 2017 https://doi.org/10.1111/medu.13437Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume51, Issue11November 2017Pages 1182-1183 RelatedInformation

Laughing and innovating.

After qualifying as a nurse at St Mary's Hospital in London in 1988, Joanna James spent 20 years working in emergency departments. She co-developed and ran a successful education programme around the needs of refugees and survivors of torture. In 2008 she changed direction and started working on improving services for people with dementia in hospital. She is now lead nurse for dementia at Imperial College Healthcare NHS Trust in London.

Excellent Dementia Care in Hospitals: A Guide to Supporting People with Dementia and their Carers James Jo Cotton Beth Knight Jules et al Excellent Dementia Care in Hospitals: A Guide to Supporting People with Dementia and their Carers 192pp £16.99 Jessica Kingsley 9781785921087 1785921088 [Formula: see text

Specialist nurse Jo James and colleagues in the dementia team at Imperial College Healthcare NHS Trust share their expertise and profound understanding of the needs of people with dementia in hospital in this useful guide for nurses and healthcare assistants.

Questions for Dr Victoria Harmer – Imperial College Healthcare NHS Trust: A Look into Cancer Nursing

Dr Victoria Harmer speaks to Roshaine Wijayatunga, Senior Editor: Oncology. Victoria Harmer is a Macmillan Consultant Nurse (breast) at Imperial College Healthcare NHS Trust. She manages nine nurse specialists and is heavily involved in service delivery and improvement for both the screening and symptomatic services. She has published over 70 articles for nursing and medical journals, as well as editing the book “Breast Cancer Nursing Care and Management”. In addition, she has written several chapters in books and acted as medical adviser for radio, television and film. In 2013, she was awarded the Nursing Times Cancer Nursing award which represents excellence in nursing and patient care. Dr Harmer has a degree in nursing from Kings College, an MBA from Westminster Business School, a doctorate from Kings and is also an Associateship of Kings College.

Transcriptional regulation and therapeutic targeting of P2X7 receptors in diabetic nephropathy

Purine P2X7 receptors are essential components of pro‐inflammatory signalling, functionally expressed on multiple immune and non‐immune cells. Renal biopsies from patients with diabetic nephropathy show widespread, glomerular mesangial expansion, immune cell infiltration and fibrosis. Here we show that in diabetic patients, renal P2X7 expression is associated with severe mesangial expansion, impaired glomerular filtration (≥40ml/min), and increased fibrosis (50%+) compared with non‐diabetic controls. P2rx7‐deficient mice developed STZ‐induced hyperglycaemia similar to controls but had reduced glomerular macrophage attraction and collagen IV deposition. Activation of P2X7 was investigated in a rat model of diabetic nephropathy. Wister rats underwent uninephrectomy and STZ‐induction. Whole kidney P2rx7 mRNA expression was increased (2.2‐fold; P&lt;0.05) compared with sham controls by 8 weeks of induction. Glomerular and interstitial macrophage accrual increased, reflecting the pathology seen in patient biopsies. Rats were then randomly selected to receive drug vehicle or selective P2X7R antagonist (AZ11657312; 50mg/kg IP) twice daily for the following 4‐weeks. P2X7R antagonism supressed transcription of pro‐inflammatory signalling molecules compared with the vehicle group, and reduced interstitial macrophage accrual. These data suggest that P2rx7 contributes to renal inflammation in diabetics and P2X7R antagonists may have therapeutic potential.Support or Funding InformationRIM is a BHF Immediate Postdoctoral Basic Science Research Fellow (Award number FS/15/60/31510). JWRB received a MRC/Kidney Research UK Joint Clinical Training Fellowship (Award number G0901956). We would like to thank GSK for gifting the P2X7k expressing gene‐targeted mice. FWKT is supported by the Diamond Fund from Imperial College Healthcare Charity. Part of this work is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London.

Meeting patients' unmet needs.

Macmillan consultant nurse (breast) Victoria Harmer qualified with distinction in 1995 and has devoted her career to caring for patients with cancer. She specialised in breast cancer 17 years ago, after taking up a clinical nurse specialist post at London's St Mary's Hospital. She has been in her current role at Imperial College Healthcare NHS Trust since October 2016, and is also a published author and script adviser for television programmes featuring breast cancer storylines.

Is the ‘Visual Fields Easy’ Application a Useful Tool to Identify Visual Field Defects in Patients Who Have Suffered a Stroke?

Aims: To determine the level of agreement between the visual Fields easy application (VFE) for iPad and a standard clinical test for assessing peripheral vision in stroke survivors. Study Design: This was a prospective cross-sectional study comparing the VFE application to the Humphrey Field Analyser (HFA) SITA Fast c30-2 program in identifying and diagnosing visual field defects post-stroke. Place and Duration of Study: The ophthalmic department at Imperial College Healthcare NHS Trust. Data collection was undertaken between January 2016 and August 2016. Methodology: A total of 50 participants with a diagnosis of stroke and a suspected visual problem were recruited to the study. Normative data was collected from 50 participants with no history of stroke or visual loss. Analysis comprised of comparing the extent of the visual field loss detected by both the VFE and HFA, and clinically assessing the results for normality. Results: Bland-Altman analysis demonstrated that with more severe visual field loss, the agreement between both modalities was found to decrease. There was a higher proportion of false negatives with the VFE compared to the HVF. The bias towards detecting more missed test locations with the VFE application compared to the HFA was 6% for the normal participants and 2% for the stroke participants. The limits of agreement between the two modalities were large; 20% and 40% for the normal and stroke participants respectively. The sensitivity of the VFE application to determine an abnormal visual field in comparison to HFA was 88% and specificity was 76% in the stroke cohort based upon a clinical impression of its findings. The majority of stroke participants (88%) found the VFE test more comfortable to perform. Conclusion: As a screening tool, the VFE application is quick and easy to administer, preferred by patients and has good sensitivity and specificity for detecting the presence of an abnormal visual field when compared to HFA. In patients with extensive visual field loss, the VFE may overestimate visual field reduction.

'Don't be afraid of failure'.

Venetia Wynter-Blyth has worked in oncology for 15 years. She spent 12 years as an upper gastrointestinal (GI) clinical nurse specialist before taking up her current post as Macmillan nurse consultant in upper GI cancers at Imperial College Healthcare NHS Trust in London. She was named RCN Nurse of the Year 2016 for creating PREPARE, a holistic 'prehabilitation' self-management programme for people with cancer who require surgery.

'Make your opportunities'.

What is your job? I am a clinical research nurse for neurosurgery, emergency and trauma at Imperial College Healthcare NHS Trust, London. My role involves supporting research in neurosurgery, emergency and trauma care. I offer guidance at all stages of the research process, from project conception to output.

Vaccines in Pregnancy: MatImms.

This app was developed by researchers and clinicians at Imperial College London and Imperial College Healthcare NHS Trust after concern about the low uptake of vaccines among pregnant women.

Taking an organisational approach to quality improvement

The challenge for all healthcare organisations is to develop and implement an approach that will enable improvements to the quality of healthcare to happen. This case study describes some of the thinking, design and learning from Imperial College Healthcare NHS Trust, on the early steps of our journey to create a culture of continuous improvement across the organisation.