An analysis of the employees’ perception of how innovative public sector provider organisations in England are and how aligned these perceptions are to their employers and overseeing governmental departments intentions

Peter Mason, Senior Delivery and Improvement Lead, NHS England and NHS Improvement is undertaking a study and is asking for NHS staff to take part by completing a short on-line survey.  The study is called "An analysis of the employees’ perception of how innovative public sector provider organisations in England are and how aligned these perceptions are to their employers and overseeing governmental departments intentions."

You are invited to complete a survey, which will show how aligned the NHS organisation’s strategic intentions of innovation are with the perceptions of staff.  If you'd like to participate, please complete the questionnaire, which should take around 20 minutes. For more information, please see the Participant Information Sheet.


For any questions, please call Peter Mason, the Chief Investigator, 07502 213839 or email him peter.mason9@nhs.net.

CCC publication: Role of Radiotherapy in the Treatment of Rectal Cancer in Older Patients

Citation: European Journal of Surgical Oncology. 2020, 46(3), 349-357
Author: Arthur Sun Myint, Jean Pierre Gérard
Abstract: Striking a balance between cancer treatment and patient-centred care is becoming ever more important in older patients with rectal cancer as the population is ageing. The treatment decision made by the modern multidisciplinary colorectal team will recommend pre-operative chemo-radiotherapy followed by surgery for advance rectal cancer and surgery alone for early rectal cancer, as the "standard of care" is surgery. However, an alternative non-surgical treatment option should be consider for older patients with rectal cancer as the surgical harm can far outweigh the potential benefits. There is published evidence that mortality is higher with increasing age. An alternative treatment option to surgery when patients are not suitable or refusing surgery is to offer them external beam radiotherapy (EBRT) or chemo radiotherapy (EBCRT). A proportion of these patients can achieve a clinical complete response (cCR) which enable adoption of 'watch and wait' strategy to avoid surgery. However, a third of patients who achieved initial cCR can develop local regrowth within the first two years. This require salvage surgery which reduces their chance of organ preservation. Contact X-ray brachytherapy (CXB) or High Dose Rate Endo Brachy Therapy (HDREBT) boost following external beam radiotherapy can improve the initial cCR rate and reduce the risk of local regrowth. Those patients with persistent residual cancer or regrowth after brachytherapy boost following EBCRT or EBRT can have salvage surgery later without compromising their chance of cure. Therefore, patients should be fully aware of their treatment options and have 'a choice' when deciding and consenting their treatment.
Keywords:  Brachytherapy; Chemo-radiotherapy; Local regrowth; Non-surgical; Rectal cancer; Watch and wait.

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CCC publication: Radiotherapy to the Primary Tumour for Patients With Metastatic Prostate Cancer: Practice-Changing Results From STAMPEDE

Citation: Clinical Oncology. 2020, 32(5), 327-329 Epub 2020 Jan 20
Author: Z I Malik, J D Fenwick

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CCC publication: Loss of BAP1 Expression Is Associated With an Immunosuppressive Microenvironment in Uveal Melanoma, With Implications for Immunotherapy Development

Citation: The Journal of Pathology. 2020 Jan 20[Online ahead of print]
Author: Carlos R Figueiredo, Helen Kalirai, Joseph J Sacco, Ricardo A Azevedo, Andrew Duckworth, Joseph R Slupsky, Judy M Coulson, Sarah E Coupland
Abstract: Immunotherapy using immune checkpoint inhibitors (ICIs) induces durable responses in many metastatic cancers. Metastatic uveal melanoma (mUM), typically occurring in the liver, is one of the most refractory tumours to ICIs and has dismal outcomes. Monosomy 3 (M3), polysomy 8q and BAP1 loss in primary uveal melanoma (pUM) are associated with poor prognoses. The presence of tumour infiltrating lymphocytes (TILs) within pUM and surrounding mUM - and some evidence of clinical responses to adoptive TIL transfer - strongly suggest that UM are indeed immunogenic despite their low mutational burden. The mechanisms that suppress TILs in pUM and mUM are unknown. We show that BAP1 loss is correlated with upregulation of several genes associated with suppressive immune responses, some of which build an immune suppressive axis, including HLA-DR, CD38, and CD74. Further, single-cell analysis of pUM by mass cytometry confirmed the expression of these and other markers revealing important functions of infiltrating immune cells in UM, most being a regulatory CD8+ T lymphocytes and tumour associated macrophages (TAMs). Transcriptomic analysis of hepatic mUM revealed similar immune profiles to pUM with BAP1 loss, including the expression of IDO1. At the protein level, we observed TAMs and TILs entrapped within peritumoral fibrotic areas surrounding mUM, with increased expression of IDO1, PD-L1 and β-catenin (CTNNB1), suggesting tumour-driven immune exclusion and hence the immunotherapy resistance. These findings aid the understanding of how the immune response is organised in BAP1- mUM, which will further enable functional validation of detected biomarkers and the development of focused immunotherapeutic approaches. This article is protected by copyright. All rights reserved.
Keywords:  CyTOF, digital spatial profiling; NanoString; immune profile; immunotherapy resistance; uveal melanoma.

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CCC publication: Obesity Is Common at Diagnosis of Childhood Pituitary Adenoma and May Persist Following Successful Treatment

Citation: Clinical Endocrinology. 2020, 92(4), 323-330
Author: Aashish Sethi, Mohammed Didi, Poonam Dharmaraj, Renuka Ramakrishnan, Senthil Senniappan, Urmi Das, Shivaram Avula, Ajay Sinha, Conor Mallucci, Kamal Weerasinghe, Christina Daousi, Catherine Gilkes, Nicola Thorp, Joanne Blair
Abstract: Objective:  There is a paucity of data describing long-term outcomes of paediatric patients with pituitary adenoma. In this report, we describe clinical features, treatment and outcomes of a paediatric cohort.
Design:  Retrospective cohort study.
Patients:  Twenty-four white Caucasian patients aged <16 years from a single tertiary care centre in the United Kingdom at diagnosis followed for (median, range) 3.3, 0.7-8.4 years.
Measurements:  Clinical and radiological data at diagnosis and follow-up.
Results:  Thirteen patients had prolactinomas (54.1%, age: 15.2 years, 13.2-15.8 years; all females), including ten macroadenomas (11.0-35.0 mm). Patients presented with menstrual disorders (91%), headache (46%), galactorrhoea (46%) and obesity (body mass index [BMI] SDS > 2): (38%). Ten patients with prolactinoma were treated with dopamine agonist alone, 3 also required surgery and 2 patients, cabergoline, surgery plus radiotherapy. Five patients had Cushing's disease (20.8%, age: 14.0, 4.0-15.7 years; 2 female), including one macroadenoma (24 mm). Patients presented with obesity (100%), short stature (60%) and headache (40%). Transsphenoidal resection resulted in biochemical cure (09.00 cortisol < 50 nmol/L). Two patients relapsed 3- and 6 years following surgery, requiring radiotherapy. One patient also required bilateral adrenalectomy. Six patients had nonfunctioning pituitary adenoma (25.0%, age: 15.8, 12.5-16.0 years; 2 female), including two macroadenomas (20.0-53.0 mm). Patients presented with obesity (67%), visual field defects (50%) and headache (50%). Four required surgical resections; two recurred following surgery and required radiotherapy. On latest follow-up; 13 (54.1%) patients were obese (BMI 3.09 SDS; range: 2.05-3.73 SDS).
Conclusion:  Obesity is common at diagnosis of pituitary adenoma in childhood and may persist despite successful treatment. Adenomas were larger, more resistant to treatment, and more likely to recur than in adult populations.
Keywords:  adolescent; child; obesity; pituitary adenoma.

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CCC publication: Lenvatinib and Sorafenib for Differentiated Thyroid Cancer After Radioactive Iodine: A Systematic Review and Economic Evaluation

Citation: Health Technology Assessment. 2020, 24(2), 1-180
Author: Nigel Fleeman, Rachel Houten, Adrian Bagust, Marty Richardson, Sophie Beale, Angela Boland, Yenal Dundar, Janette Greenhalgh, Juliet Hounsome, Rui Duarte, Aditya Shenoy
Abstract: Background:  Thyroid cancer is a rare cancer, accounting for only 1% of all malignancies in England and Wales. Differentiated thyroid cancer (DTC) accounts for ≈94% of all thyroid cancers. Patients with DTC often require treatment with radioactive iodine. Treatment for DTC that is refractory to radioactive iodine [radioactive iodine-refractory DTC (RR-DTC)] is often limited to best supportive care (BSC).
Objectives:  We aimed to assess the clinical effectiveness and cost-effectiveness of lenvatinib (Lenvima®; Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar®; Bayer HealthCare, Leverkusen, Germany) for the treatment of patients with RR-DTC.
Data sources:  EMBASE, MEDLINE, PubMed, The Cochrane Library and EconLit were searched (date range 1999 to 10 January 2017; searched on 10 January 2017). The bibliographies of retrieved citations were also examined.
Review methods:  We searched for randomised controlled trials (RCTs), systematic reviews, prospective observational studies and economic evaluations of lenvatinib or sorafenib. In the absence of relevant economic evaluations, we constructed a de novo economic model to compare the cost-effectiveness of lenvatinib and sorafenib with that of BSC.
Results:  Two RCTs were identified: SELECT (Study of [E7080] LEnvatinib in 131I-refractory differentiated Cancer of the Thyroid) and DECISION (StuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine-refractory thyrOid caNcer). Lenvatinib and sorafenib were both reported to improve median progression-free survival (PFS) compared with placebo: 18.3 months (lenvatinib) vs. 3.6 months (placebo) and 10.8 months (sorafenib) vs. 5.8 months (placebo). Patient crossover was high (≥ 75%) in both trials, confounding estimates of overall survival (OS). Using OS data adjusted for crossover, trial authors reported a statistically significant improvement in OS for patients treated with lenvatinib compared with those given placebo (SELECT) but not for patients treated with sorafenib compared with those given placebo (DECISION). Both lenvatinib and sorafenib increased the incidence of adverse events (AEs), and dose reductions were required (for > 60% of patients). The results from nine prospective observational studies and 13 systematic reviews of lenvatinib or sorafenib were broadly comparable to those from the RCTs. Health-related quality-of-life (HRQoL) data were collected only in DECISION. We considered the feasibility of comparing lenvatinib with sorafenib via an indirect comparison but concluded that this would not be appropriate because of differences in trial and participant characteristics, risk profiles of the participants in the placebo arms and because the proportional hazard assumption was violated for five of the six survival outcomes available from the trials. In the base-case economic analysis, using list prices only, the cost-effectiveness comparison of lenvatinib versus BSC yields an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £65,872, and the comparison of sorafenib versus BSC yields an ICER of £85,644 per QALY gained. The deterministic sensitivity analyses show that none of the variations lowered the base-case ICERs to < £50,000 per QALY gained.
Limitations:  We consider that it is not possible to compare the clinical effectiveness or cost-effectiveness of lenvatinib and sorafenib.
Conclusions:  Compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. Both treatments exhibit estimated ICERs of > £50,000 per QALY gained. Further research should include examination of the effects of lenvatinib, sorafenib and BSC (including HRQoL) for both symptomatic and asymptomatic patients, and the positioning of treatments in the treatment pathway.
Study registration:  This study is registered as PROSPERO CRD42017055516.
Funding:  The National Institute for Health Research Health Technology Assessment programme.
Keywords:  IODINE RADIOISOTOPES; LENVATINIB; MODELS, ECONOMIC; SORAFENIB; SYSTEMATIC REVIEW; THERAPEUTIC USE; THYROID NEOPLASMS.

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CCC publication: The Role of Multidisciplinary Decision Making in Oropharyngeal Cancer: Do We Follow Guidelines and Are Treatment Decisions Being Implemented?

Citation: European archives of Otorhinolaryngology. 2020, 277(3), 947-952
Author: Randa Ghazal Asswad, Sirhan Alvi, Katharine Davies, Terry M Jones, David W Hamilton, Caroline Brammer, Jeffrey Lancaster, Christopher Loh, Sankalap Tandon, Nick Roland
Abstract: Purpose:  A multidisciplinary team (MDT) approach to cancer management is gold-standard. With an increasing disease incidence and growing research into human papillomavirus (HPV)-related oropharyngeal cancer (OPC), updated UK management guidelines were recently published. This study aimed to evaluate the MDT decision-making process among OPC patients at a tertiary centre.
Methods:  MDT meetings over a 12-month period were analysed retrospectively. MDT decisions were compared with guidelines and patient records examined to identify decision implementation. Reasons behind any discordant decisions were explored.
Results:  This study included 140 OPC patients. Thirty-three (23.6%) were not tested for HPV. Patients over 70 years with a smoking history treated palliatively were less likely to be tested (P = 0.017). Eighty-five percent of MDT decisions followed guidelines with the majority not complying (76.2%) related to patient comorbidity. Ten decisions (7.1%) were not implemented. Reasons included: Seven due to patient choice, of which four patients (57.1%) were only seen following the MDT meeting, and three due to clinician decisions as new clinical information emerged.
Conclusion:  The majority of MDT decisions followed guidelines and any discordant decisions were justifiable. Discussing management options with patients beforehand facilitates decision implementation as decisions can potentially change after seeing the patient. Progress is still needed with regards to HPV testing. Reasons for not testing could include subliminal decision-making among clinicians, and patients falling between centres. Crucially, the role of the MDT in head and neck cancer should be to ratify decisions rather than making them, hence the need to see patients prior to MDT discussion.
Keywords:  Decision implementation; Decision making; Human papillomavirus; Multi-disciplinary team; Oropharyngeal neoplasms; Patient preference.

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CCC publication: CD40L Membrane Retention Enhances the Immunostimulatory Effects of CD40 Ligation

Citation: Scientific Reports. 2020, 10(1), 342
Author: Taha Elmetwali, Asmaa Salman, Wenbin Wei, Syed A Hussain, Lawrence S Young, Daniel H Palmer
Abstract: In carcinomas, the nature of CD40 ligand shapes the outcome of CD40 ligation. To date, the consequences of membrane-bound CD40L (mCD40L) on its immune-stimulatory function are unknown. Here, we examined the impact of mCD40L versus soluble CD40L (sCD40L) on T24 bladder carcinoma gene expression profiling. Of 410 differentially expressed genes, 286 were upregulated and 124 downregulated by mCD40L versus sCD40L. Gene ontology enrichment analysis revealed immune-stimulatory function as the most significant enriched biological process affected by upregulated transcripts, while those downregulated were critical for cell growth and division. Furthermore, immature dendritic cells (iDC) responded to mCD40L with enhanced maturation and activation over sCD40L evidenced by higher expression levels of CD83, CD86, HLA-DR and CD54, increased secretion of IL12 and IL10 and higher tumour-antigen (TA) uptake capacity. Furthermore, autologus CD3+ T cells responded to TA-loaded mCD40L-activated DC with increased proliferation and cytotoxic response (CD107a and IFN-γ-producing CD3+ CD8+ T cells) to the tumour-loaded autologous PBMCs compared to sCD40L. Thus, these data indicate that mCD40L enhances the immunostimulatory capacity over sCD40L. Furthermore, the ability of mCD40L to also directly induce cell death in CD40-expressing carcinomas, subsequently releasing tumour-specific antigens into the tumour microenvironment highlights the potential for mCD40L as a multi-faceted anti-cancer immunotherapeutic.

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CCC publication: Molecular MRD status and outcome after transplantation in NPM1 mutated AML: results from the UK NCRI AML17 study

Citation: Blood. 2020 Jan 13[Online ahead of print]
Author: Richard Dillon, Robert K Hills, Sylvie D Freeman, Nicola Potter, Jelena Jovanovic, Adam Ivey, Anju Shankar Kanda, Manohursingh Runglall, Nicola Foot, Mikel Valganon, Asim Khwaja, Jamie Cavenagh, Matthew L Smith, Hans Beier Ommen, Ulrik Overgaard, Mike Dennis, Steven Knapper, Harpreet Kaur, David C Taussig, Priyanka Mehta, Kavita Raj, Igor Novitzky-Basso, Emmanouil Nikolousis, Robert D Danby, Pramila Krishnamurthy, Kate Hill, Damian Finnegan, Samah Alimam, Erin Hurst, Peter Johnson, Anjum Bashir Khan, Rahuman Salim, Charles F Craddock, Ruth Lilian Spearing, Amanda Frances Gilkes, Rosemary E Gale, Alan Kenneth Burnett, Nigel H Russell, David Grimwade
Abstract: Relapse remains the most common cause of treatment failure for patients with acute myeloid leukaemia (AML) who undergo allogeneic stem cell transplantation (alloSCT) and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry (FCM) prior to alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays which have far greater sensitivity. We analysed pre-transplant blood and bone marrow samples by reverse-transcription polymerase chain reaction (RT-qPCR) in 107 patients with NPM1 mutant AML enrolled in the UK National Cancer Research Institute (NCRI) AML17 study. After a median follow-up of 4.9 years, patients with negative, low (<200 copies / 105 ABL in the PB and <1000 copies in the BM) and high levels of MRD had an estimated 2y overall survival (OS) of 83%, 63% and 13% respectively (p<0.0001). Focussing on patients with low level MRD prior to alloSCT, those with FLT3 ITD had significantly poorer outcome (hazard ratio, HR, 6.14, p=0.01). Combining these variables was highly prognostic, dividing patients into two groups with 2y OS of 17% and 82% (HR 13.2, p<0.0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y OS 56% vs 96%, HR 3.24, p=0.0005) and in MRD positive patients (2y OS 34% vs 100%, HR 3.78, p=0.003) but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).

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CCC publication: Digitising a consultant radiographer led palliative radiotherapy service,

Citation: Radiography. 2020, 26(Sup1), S22
Author: Conor Fitzpatrick,

CCC publication: Improving patient pathways in head and neck cancer at a UK Cancer Centre. Results of a dietetic pre-treatment project (DPP)

Citation: Clinical Nutrition ESPEN. 2020, 35, 250
Author: Parr K.; Johnson F.; Langley N.; Richardson P.

CCC publication: Evaluation of erectile potency and radiation dose to the penile bulb using image guided radiotherapy in the CHHiP trial,

Citation: Clinical and Translational Radiation Oncology. 2019 Dec 31, 21, 77-84. eCollection Mar 2020
Author: J. Murray, S. Gulliford, C. Griffin, A. Wilkins, I. Syndikus, J. Staffurth, M. Panades, C. Scrase, C. Parker, V. Khoo, J. Dean, H. Mayles, P. Mayles, S. Thomas, O. Naismith, H. Mossop, C. Cruickshank, E. Hall, D. Dearnaley
Abstract: Background and purpose:  The penile bulb (PB) dose may be critical in development of post prostate radiotherapy erectile dysfunction (ED). This study aimed to generate PB dose constraints based on dose-volume histograms (DVHs) in patients treated with prostate radiotherapy, and to identify clinical and dosimetric parameters that predict the risk of ED post prostate radiotherapy.
Materials and methods:  Penile bulb DVHs were generated for 276 patients treated within the randomised IGRT substudy of the multicentre randomised trial, CHHiP. Incidence of ED in relation to dose and randomised IGRT groups were evaluated using Wilcoxon rank sum, Chi-squared test and atlases of complication incidence. Youden index was used to find dose-volume constraints that discriminated for ED. Multivariate analysis (MVA) of effect of dosimetry, clinical and patient-related variables was performed.
Results:  Reduced treatment margins using IGRT (IGRT-R) produced significantly reduced mean PB dose compared with standard margins (IGRT-S) (median: 25 Gy (IGRT-S) versus 11 Gy (IGRT-R); p < 0.0001). Significant difference in both mean (median: 23 Gy (ED) vs. 18 Gy (no ED); p = 0.011) and maximum (median: 59 Gy (ED) vs. 52 Gy (no ED); p = 0.018) PB doses between those with and without clinician reported ED were identified. Mean PB dose cut-point for ED was derived at around 20 Gy. On MVA, PB mean dose and age predicted for impotence.
Conclusion:  PB dose appears predictive of post-radiotherapy ED with calculated threshold mean dose of around 20 Gy, substantially lower than published recommendations. IGRT-R enables favourable PB dosimetry and can be recommended provided prostate coverage is not compromised.
Keywords:  Erectile dysfunction; Image-guided radiotherapy; Penile bulb; Prostate.

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CCC publication: CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases (CARBON): study protocol for a phase IB/IIA randomised controlled trial.

Citation: Trials. 2020, 21(1), 89
Author: Rob Coleman, Janet Brown, Emma Rathbone, Louise Flanagan, Amber Reid, Jessica Kendall, Sacha Howell, Chris Twelves, Carlo Palmieri, Anjana Anand, Iain MacPherson, Sarah Brown
Abstract: Background:  A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement. Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.
Methods/design:  CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.
Discussion:  The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.
Trial registration:  ISRCTN, ISRCTN92755158, Registered on 17 February 2016.
Keywords:  Bone metastases; Bone turnover markers; Breast cancer; Capecitabine; Radium-223

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CCC publication: Development of an orthotopic syngeneic murine model of colorectal cancer for use in translational research

Citation: Laboratory Animals. 2019, 53(6), 598-609
Author: Evans J.P. (jpevans@liverpool.ac.uk); Sutton P.A.; Palmer D.H.; Winiarski B.K.; Goldring C.E.; Kitteringham N.R.; Ressel L.; Duckworth C.A.; Pritchard D.M.
Abstract: Improving outcomes in colorectal cancer requires more accurate in vivo modelling of the disease in humans, allowing more reliable pre-clinical assessment of potential therapies. Novel imaging techniques are necessary to improve the longitudinal assessment of disease burden in these models, reducing the number of animals required for translational studies. This report describes the development of an immune-competent syngeneic orthotopic murine model of colorectal cancer, utilising caecal implantation of CT26 cells stably transfected with the luciferase gene into immune-competent BALB/c mice, allowing serial bioluminescent imaging of cancer progression. Luminescence in the stably transfected CT26 cell line, after pre-conditioning in the flank of a BALB/c mouse, accurately reflected cell viability and resulted in primary caecal tumours in five of eight (63%) mice in the initial pilot study following caecal injection. Luminescent signal continued to increase throughout the study period with one mouse (20%) developing a liver metastasis. Histopathological assessment confirmed tumours to be consistent with a poorly differentiated adenocarcinoma. We have now performed this technique in 68 immune-competent BALB/c mice. There have been no complications from the procedure or peri-operative deaths, with primary tumours developing in 44 (65%) mice and liver metastases in nine (20%) of these. This technique provides an accurate model of colorectal cancer with tumours developing in the correct microenvironment and metastasising to the liver with a similar frequency to that seen in patients presenting with colorectal cancer, with serial bioluminescent reducing the murine numbers required in studies by removing the need for cull for assessment of disease burden.
KEYWORDS: Colorectal cancer; bioluminescent imaging; orthotopic syngeneic model

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WUTH publication: 'Tax-otsubo': stress cardiomyopathy following an encounter with the Inland Revenue

Citation: BMJ Case Reports. 2020, 13(1),  e232225
Author: Roach MW, Currie P
Abstract: An 89-year-old man developed chest pain and palpitations shortly after finishing a stressful 40 min phone call to HM Revenue and Customs. After admission to the emergency department, he had a cardiovascular collapse followed soon after by a cardiac arrest due to ventricular fibrillation (VF). The troponin T was elevated and his ECG showed extensive deep T wave inversion with prolongation of the QT interval. A portable hand-held ultrasound device (VScan; GE Healthcare) was used to demonstrate classical apical ballooning of the left ventricular apex indicating a diagnosis of takotsubo stress cardiomyopathy. Shortly following admission to the cardiac care unit, he had a further episode of VF, which was successfully defibrillated. A coronary angiogram was performed, which was normal. He was treated with a short course of benzodiazepines. He was discharged after 8 days without any neurological deficit. His echocardiogram subsequently showed complete resolution of the abnormalities of the left ventricular function.
© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS: arrhythmias; clinical diagnostic tests; heart failure

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Notification of scheduled maintenance to BMJ websites

On Saturday 11th January 2020 (0900 to 1700 GMT), a number of BMJ websites will be undergoing maintenance. This will mean that the following websites will be unavailable for approximately 8 hours: BMJ Best Practice (offline access will be available via the app) BMJ Learning Research to Publication  Information for users will be posted on our sites before and during the scheduled downtime. BMJ runs a policy of continuous improvement in its hosting environments and we will be using this time to complete a project to migrate our hosting services to a more modern, scalable platform. This will result in an improvement in the reliability, robustness and performance of BMJ websites. Thank you for your patience and understanding. If you have any questions, please speak to your account manager or contact support.bmj.com.

WUTH publication: An investigation into the avoidability of adverse drug reactions using the LAAT and modified Hallas tools

Citation: Medicine (Baltimore). 2020, 99(1), e18569
Author: Danjuma MI, Shokri SA, Abubeker IY, Malik AE, Abdallah IMH, Shafei MNE, Fatima H, Mahmoud M, Hussain T, Maghoub Y, Sajid J, Zouki ANE
Abstract: An adverse drug reactions avoidability tool called the Liverpool ADR avoidability assessment tool (LAAT) was recently developed (for research purposes), and subsequently validated with mixed interrater reliability (IRR). We investigated the comparative IRR of this tool in an inpatient cohort to ascertain its practical application in this setting.The patient population was comprised of 44 ADR drug pairs drawn from an observational prospective cohort of patents with ADR attending a Weill Cornell Medicine-affiliated tertiary medical Centre in Doha Qatar (Hamad General Hospital). Using the LAAT, and modified Hallas tools, 4 independent raters (2 Clinical Pharmacologists, and 2 General Physicians) assessed and scored the 44 ADR-drug pairs. Agreement proportions between the rating pairs were evaluated as well individual/overall kappa statistics and intraclass correlation coefficients. We evaluated the weight of each of the 7 questions on the LAAT tool to ascertain its determinative role.Across 44 ADR-drug pairs, the overall median Fleiss kappa using the LAAT, and modified Hallas tools were 0.67 (interquartile range (IQR) 0.55, 0.76), 0.36 (IQR, 0.23-0.71) respectively. The overall percentage pairwise agreement with the LAAT and modified Hallas tools were 78.5%, and 62.2% respectively. Exact pairwise agreement occurred in 37 out of 44 (range 0.71-1), and 27 of 44 (0.53-0.77) ADR-drug pairs using the LAAT and modified Hallas tools respectively. Using the LAAT tool, the overall intraclass correlation coefficient was 0.68 (CI 0.55, 0.79), and 0.37 (CI 0.22, 0.53) with the modified Hallas tool.We report a higher proportion of "possible" and "definite" avoidability outcomes of adverse drug reactions compared with the modified Hallas, or that reported by developers of the LAAT tool. Although initially developed for research purposes, our report has suggested for the first time a potential applicability of this tool in clinical environment as well.

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