Tracking

Thursday, 22 October 2020

WUTH publication: Is "no test is better than a bad test"? Impact of diagnostic uncertainty in mass testing on the spread of COVID-19

Citation: PLoS one. 2020, 15(10), e0240775
Author: Gray N, Calleja D, Wimbush A, Miralles-Dolz E, Gray A, De Angelis M, Derrer-Merk E, Oparaji BU, Stepanov V, Clearkin L, Ferson S
Abstract: Testing is viewed as a critical aspect of any strategy to tackle epidemics. Much of the dialogue around testing has concentrated on how countries can scale up capacity, but the uncertainty in testing has not received nearly as much attention beyond asking if a test is accurate enough to be used. Even for highly accurate tests, false positives and false negatives will accumulate as mass testing strategies are employed under pressure, and these misdiagnoses could have major implications on the ability of governments to suppress the virus. The present analysis uses a modified SIR model to understand the implication and magnitude of misdiagnosis in the context of ending lockdown measures. The results indicate that increased testing capacity alone will not provide a solution to lockdown measures. The progression of the epidemic and peak infections is shown to depend heavily on test characteristics, test targeting, and prevalence of the infection. Antibody based immunity passports are rejected as a solution to ending lockdown, as they can put the population at risk if poorly targeted. Similarly, mass screening for active viral infection may only be beneficial if it can be sufficiently well targeted, otherwise reliance on this approach for protection of the population can again put them at risk. A well targeted active viral test combined with a slow release rate is a viable strategy for continuous suppression of the virus.

Thursday, 15 October 2020

WUTH publication: Acute ischaemic stroke management: Concepts and Controversies. A narrative review

Citation: Expert review of neurotherapeutics. 2020 Oct 13. Online ahead of print
Author: Li KHC, Jesuthasan A, Kui C, Davies R, Tse G, Lip GYH
Abstract: Introduction: Amongst the 25.7 million survivors and 6.5 million deaths from stroke between 1990 and 2013, ischemic strokes accounted for approximately 70% and 50% of the cases, respectively. With patients still suffering from complications and stroke recurrence, more questions have been raised as to how we can better improve patient management.
Areas covered: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Newcastle-Ottawa Scale (NOS) were adopted to ensure a comprehensive inclusion of quality literature from various sources. PubMed and Embase were searched for evidence on thrombolysis, mechanical thrombectomy, artificial intelligence (AI), antiplatelet therapy, anticoagulation and hypertension management.
Expert opinion: The directions of future research in these areas are dependent on the current level of validation. Endovascular therapy and applications of AI are relatively new compared to the other areas discussed in this review. As such, it is important for future studies to focus on validating their efficacy. As for thrombolysis, antiplatelet and anticoagulation therapy, their efficacy has been well-established and future research efforts should be directed towards adjusting its use according to patient specific factors, starting with factors with the most clinical relevance and prevalence.
Keywords: Stroke; anticoagulation; antiplatelet; artificial intelligence; thrombectomy; thrombolysis.

Friday, 9 October 2020

Visit the library

Please do come along and visit the McArdle Library.

We have a number of measures in place to limit COVID. Please:

·         wear a face mask

·         sign the visitor's book

·         sanitise hands frequently & use wipes provided to clean PCs/desk

·         observe social distancing

Let's work together & keep everyone safe

Friday, 2 October 2020

WUTH publication: Guidance for the assessment and management of prostate cancer treatment-induced bone loss. A consensus position statement from an expert group

Citation: Journal of Bone Oncology. 2020, 25, 100311
Author: Brown JE, Handforth C, Compston JE, Cross W, Parr N, Selby P, Wood S, Drudge-Coates L, Walsh JS, Mitchell C, Collinson FJ, Coleman RE, James N, Francis R, Reid DM, McCloskey E
Abstract: Context and objective: Incidence of prostate cancer (PC) is increasing, but androgen deprivation therapy (ADT) and other therapies are substantially improving survival. In this context, careful consideration of skeletal health is required to reduce the risk of treatment-related fragility fractures and their associated morbidity and mortality. This risk is currently not well-managed. ADT causes significant loss of bone mineral density (BMD). In the metastatic setting, systemic treatments (e.g. chemotherapy, abiraterone, enzalutamide) are used alongside ADT and may require concomitant glucocorticoids. Both ADT and glucocorticoids pose significant challenges to skeletal health in a population of patients already likely to have ongoing age-related bone loss and/or comorbid conditions. Current PC guidelines lack specific recommendations for optimising bone health. This guidance presents evidence for assessment and management of bone health in this population, with specific recommendations for clinical practitioners in day-to-day PC management.
Methods: Structured meetings of key opinion leaders were integrated with a systematic literature review. Input and endorsement was sought from patients, nursing representatives and specialist societies.
Summary of guidance: All men starting or continuing long-term ADT should receive lifestyle advice regarding bone health. Calcium/vitamin D supplementation should be offered if required. Fracture risk should be calculated (using the FRAX® tool), with BMD assessment included where feasible. BMD should always be assessed where fracture risk calculated using FRAX® alone is close to the intervention threshold. Intervention should be provided if indicated by local or national guidelines e.g. UK National Osteoporosis Guideline Group (NOGG) thresholds. Men requiring bone protection therapy should be further assessed (e.g. renal function), with referral to specialist centres if available and offered appropriate treatment to reduce fracture risk. Those near to, but below an intervention threshold, and patients going on to additional systemic therapies (particularly those requiring glucocorticoids), should have FRAX® (including BMD) repeated after 12-18 months.
Patient summary: Modern treatments for prostate cancer have led to significant improvements in survival and quality of life. However, some of these treatments may lead to weakening of patient's bones with risk of fracture and it is therefore important to monitor patients' bone health and provide bone protection where needed. This paper provides specific guidance to clinical teams, based on the most recent research evidence, to ensure optimal bone health in their patients.
Keywords: Fracture risk; Guidelines; Osteoporosis; Prostate cancer; Skeletal health.

WUTH publication: A prospective, multi-centre external validation study of the Liverpool Peritonsillar abscess Score (LPS) with a no-examination Covid-19 modification

Citation: Clinical Otolaryngology. 2020 Sep 30. Online ahead of print.
Author: Selwyn D, Yang D, Heward E, Kerai A, Thompson E, Shommakhi A, Faulkner S, Siau R, Walijee H, Hampton T, Chudek D, Singhera S, Din W, Lau AS
Abstract: Objectives: Our primary aim was to validate the Liverpool Peritonsillar abscess Score (LPS) externally in a new patient cohort. Our secondary aim was to modify the LPS in the light of the Covid-19 pandemic to produce a no-examination variant for use in this instance.
Design: Prospective, multicentre external validation study SETTING: Six different secondary care institutions across the United Kingdom PARTICIPANTS: Patients over 16 years old who were referred to ENT with any uncomplicated sore throat such a tonsillitis or peritonsillar abscess (PTA) MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value and negative predictive value for both the original LPS model and the modified model for Covid-19.
Results: The LPS model had sensitivity and specificity calculated at 98% and 79% respectively. The LPS has a high negative predictive value (NPV) of 99%. The positive predictive value (PPV) was slightly lower at 63%. Receiver operating characteristic (ROC) curve, including the area under the curve (AUROC) was0.888 which indicates very good accuracy.
Conclusions: External validation of the LPS against an independent, geographically diverse population yields high NPV. This may support non-specialist colleagues who may have concerns about mis-diagnosing a PTA. The Covid-19 Modification of the LPS has a similar NPV, which may be of use where routine oral examination is to be avoided during the Covid-19 pandemic.
Keywords: Peri-tonsillar abscess; diagnosis; dysphagia; swallowing.

Tuesday, 29 September 2020

WUTH publication: Refocusing cancer multidisciplinary team meetings in the United Kingdom: comparing urology with other specialties

Citation: Annals of the Royal College of Surgeons of England. 2021, 103(1), 10-17.  Epub 2020 Sep 28
Author: Warner R, Hoinville L, Pottle E, Taylor C, Green J
Abstract: INTRODUCTION: Multidisciplinary team (MDT) meetings have been the gold standard of cancer care in the UK since the 1990s. We aimed to identify the views of urology cancer MDT members in the UK on improving the functioning of meetings and compare them with those of other specialties to manage the increasing demand on healthcare resources and enhance the care of complex cancer cases. 
METHODS: We analysed data from 2 national surveys distributed by Cancer Research UK focusing on the views of 2294 and 1258 MDT members about cancer MDT meetings. 
FINDINGS: Most breast, colorectal, lung and urology cancer MDT members felt meetings could be improved in the following areas: time for meeting preparation in job plans, streamlining of patients, auditing meeting decisions and prioritising complex cases. Most urology respondents (87%) agreed some patients could be managed outside a full MDT discussion, but this was lower for other specialties (lung 78%, breast 75%, colorectal 64%). 
CONCLUSIONS: To facilitate decisions on which patients require discussion in an MDT meeting, factors adding to case complexity across all tumour types were identified, including rare tumour type, cognitive impairment and previous treatment failure. This study confirms that urology MDT members are supportive of changing from reviewing all new cancer diagnoses to discussing complex cases but managing others with a more protocolised pathway. The mechanisms for how to do this and how to ensure the safety of patients require further clarification.

Link to PubMed record


WUTH publication: The Critical Roles and Mechanisms of Immune Cell Death in Sepsis

Citation: Front Immunol. 2020, 11, 1918
Author: Cheng Z, Abrams ST, Toh J, Wang SS, Wang Z, Yu Q, Yu W, Toh CH, Wang G
Abstract: Sepsis was first described by the ancient Greek physicians over 2000 years ago. The pathophysiology of the disease, however, is still not fully understood and hence the mortality rate is still unacceptably high due to lack of specific therapies. In the last decade, great progress has been made by shifting the focus of research from systemic inflammatory response syndrome (SIRS) to multiple organ dysfunction syndrome (MODS). Sepsis has been re-defined as infection-induced MODS in 2016. How infection leads to MODS is not clear, but what mediates MODS becomes the major topic in understanding the molecular mechanisms and developing specific therapies. Recently, the mechanism of infection-induced extensive immune cell death which releases a large quantity of damage-associated molecular patterns (DAMPs) and their roles in the development of MODS as well as immunosuppression during sepsis have attracted much attention. Growing evidence supports the hypothesis that DAMPs, including high-mobility group box 1 protein (HMGB1), cell-free DNA (cfDNA) and histones as well as neutrophil extracellular traps (NETs), may directly or indirectly contribute significantly to the development of MODS. Here, we provide an overview of the mechanisms and consequences of infection-induced extensive immune cell death during the development of sepsis. We also propose a pivotal pathway from a local infection to eventual sepsis and a potential combined therapeutic strategy for targeting sepsis.
Keywords: sepsis, extensive immune cell death, damage-associated molecular patterns (DAMPs), multiple organ dysfunction syndrome (MODS), extracellular histones, immunosuppression

Friday, 25 September 2020

CCC publication: Beam characterisation studies of the 62 MeV proton therapy beamline at the Clatterbridge Cancer Centre

Citation: Physica Medica. 2020, 77, 108-20
Author: Yap J. (jacinta.yap@liverpool.ac.uk); Resta-Lopez J.; Schnuerer R.; Welsch C.; Kacperek A.; Jolly S.; Boogert S.
Abstract: The Clatterbridge Cancer Centre (CCC) in the United Kingdom is the world's first hospital proton beam therapy facility, providing treatment for ocular cancers since 1989. A 62 MeV beam of protons is produced by a Scanditronix cyclotron and transported through a passive delivery system. In addition to the long history of clinical use, the facility supports a wide programme of experimental work and as such, an accurate and reliable simulation model of the treatment beamline is highly valuable. However, as the facility has seen several changes to the accelerator and beamline over the years, a comprehensive study of the CCC beam dynamics is needed to firstly examine the beam optics. An extensive analysis was required to overcome facility related constraints to determine fundamental beamline parameters and define an optical lattice written with the Methodical Accelerator Design (MAD-X) and the particle tracking Beam Delivery Simulation (BDSIM) code. An optimised case is presented and simulated results of the optical functions, beam distribution, losses and the transverse rms beam sizes along the beamline are discussed. Corresponding optical and beam information was used in TOPAS to simulate transverse beam profiles and compared to EBT3 film measurements. We provide an overview of the magnetic components, beam transport, cyclotron, beam and treatment related parameters necessary for the development of a present day optical model of the facility. This work represents the first comprehensive study of the CCC facility to date, as a basis to determine input beam parameters to accurately simulate and completely characterise the beamline. Copyright © 2020 Associazione Italiana di Fisica Medica

CCC publication: Proton ocular centers with dedicated fixed low-energy beams: Key concepts for new centers

Citation: Investigative Ophthalmology and Visual Science. 2020, 61(7). (Conference Abstract)
Author: Mishra K.K.; Daftari I.; Scholey J.; Quivey J.; Kacperek A.; Afshar A.R.; Damato B.; Char D.
Abstract: Purpose : Proton beam treatment for uveal melanoma (UM) has been well established internationally with dedicated ocular beamlines. With the emergence of universal, high-energy, non-fixed beamlines, we share key practices to minimize side effects. Methods : The University of California, San Francisco (UCSF), USA, and the Clatterbridge Cancer Centre (CCC), UK, both have longstanding facilities with dedicated, fixed, low-energy, ocular lines, which produce 67.5 and 60.0 MeV proton beams, respectively (range up to 3 cm). In total 5927 ocular patients, 93% with UM, have been treated. Standard UM dose is 56 Gray Equivalent (GyE) at UCSF and 57.2 GyE at CCC, delivered in 4 fractions. Planning and delivery procedures were analyzed as a bi-institutional effort to communicate key concepts to developing centers. Results : Low-energy dedicated eye beamlines provide critical beam characteristics for normal eye tissue sparing. Both centers offer a very sharp dose fall off (distal ~1 mm and lateral ~1.1-1.6 mm), high dose homogeneity, excellent range precision and short treatment time (~0.5-2 minutes). Analyses confirm that planned doses to critical ocular structures are independent predictors of vision, neovascular glaucoma, and other clinical outcomes (e.g. 28 GyE to macula [P<.0001], optic nerve [P<0.0004], lens [P<.0001], and ciliary body [P<.0001]). A rational tumor/critical structure dose evaluation is used to optimize treatment parameters, i.e. lateral margin, distal range, gaze angle, and aperture shape. New high-energy non-dedicated beam designs, which degrade energy to deliver ocular treatment, may require significant beam adjustment and treatment planning procedures to achieve adequate characteristics. A common dosing regimen for UM is 60 GyE in 4 fractions globally. Unrandomized early retrospective data showed lower local tumor control with 48 GyE (P=0.02). Critical structures including the retina, lacrimal gland, cornea, tear ducts, lids, bony orbit, and limbal stem cells are systematically evaluated to minimize side effects. Eyelid toxicity is minimized by retraction techniques or treatment through closed lids. Conclusions : Experienced proton centers at UCSF and CCC with dedicated, low-energy, fixed eyelines, provide important practical clinical concepts for consideration by new centers to optimize high-energy universal beamline designs, particularly to reduce normal tissue toxicity.

CCC publication: Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma

Citation: BMJ Open. 2020, 10(9), e038892
Author: Lim E. (e.lim@rbht.nhs.uk); Darlison L.; Edwards J.; Elliott D.; Mills N.; Fennell D.A.; Popat S.; Rintoul R.C.; Waller D.; Lau K.; Ali C.; Bille A.; Fuller L.; Ionescu A.; Keni M.; Kirk A.; Koh P.; Mansy T.; Maskell N.A.; Milton R.; Muthukumar D.; Pope T.; Roy A.; Shah R.; Shamash J.; Tasigiannopoulos Z.; Taylor P.; Treece S.; Ashton K.; Harris R.; Joyce K.; Warnes B.; Rogers C.; Stokes E.A.
Abstract: Introduction: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left.
Methods and analysis: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery—(extended) pleurectomy decortication—versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.
Ethics and dissemination: Research ethics approval was granted by London – Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal.
Trial registration numbers: ISRCTN—ISRCTN44351742 and ClinicalTrials.gov—NCT02040272.
Keywords: oncology, chemotherapy, thoracic surgery, thoracic medicine