Author: Jason Curtis

Global longitudinal strain detects trastuzumab induced cardiotoxicity early in a clinical population (2020)

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Type of publication:
Conference abstract

Author(s):
*Grylls, J., *Ellis, C., *Ingram, T., *Lee, E.

Citation:
European Heart Journal – Cardiovascular Imaging 2020; Volume 21, Issue Supplement 1

Abstract:
Background: Trastuzumab is highly effective in the treatment of breast cancer, and is often used as an adjuvant therapy. Due to its potential cardiotoxicity, serial monitoring of cardiac function is vital. Ejection fraction (EF) by two-dimensional echocardiography is routinely used but has limitations in measurement variability. Myocardial deformation imaging, in particular Global Longitudinal Strain (GLS), can detect pre-clinical myocardial dysfunction. However, its use is not yet adopted into routine clinical practice.
Aims: Our aim was to ascertain if a clinically significant reduction in GLS (≥11% from baseline) occurred before the onset of EF reduction, in patients who developed cardiotoxicity whilst receiving trastuzumab.
Methods: Between January 2014 and January 2019, 235 consecutive patients received trastuzumab and underwent serial echocardiography at 3 monthly intervals at our institute. Cardiotoxicity is defined as a ≥10% EF reduction from baseline or an EF <50%. Women who developed cardiotoxicity as defined by this change in EF were retrospectively studied.Two-dimensional speckle tracking was used to derive peak longitudinal strain in each myocardial segment from the apical four-, three- and two-chamber view images. GLS was taken as the average value of all these segments. The median time to ≥11% GLS reduction and ≥10% EF reduction or EF <50% was compared.
Results: Thirteen women (mean age 53 ± 9.5 years) developed cardiotoxicity. EF was 61.8 ± 4.4% at baseline and 45.7 ± 7.5% following therapy (p = 0.00). A ≥11% reduction in GLS from baseline was observed in all patients: GLS -20.2 ± 1.5% and -15.6 ± 2.1%, p = 0.00. The median time to cardiotoxicity as defined by EF and GLS was 6 months and 3 months, respectively (p = 0.031), as shown in Table 1. Repeatability analysis showed both EF and GLS measurements in our cohort have good measurement reproducibility. Inter-observer intraclass correlation (ICC) for EF and GLS were 0.912 and 0.913, respectively. Intra-observer ICC for EF and GLS were 0.925 and 0.900, respectively.
Conclusion: Cardiotoxicity developed in a significant portion (6%) of our patients receiving trastuzumab. As a reduction in GLS was detectable early and preceded that of EF by 3 months, this may represent a therapeutic window for initiation of cardio-protective medication, if and when the use of GLS is incorporated into routine practice for cardiotoxicity surveillance.

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The use of mouthguards in grappling sports: a survey of grapplers in the United Kingdom (2019)

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Type of publication:
Journal article

Author(s):
*Razzak, Arif., *Messahel, Ahmed

Citation:
British Dental Journal 2019; Vol. 227, pages 901–905

Abstract:
Background: Mouthguards are routinely used in many sports, however their use in grappling sports has not really been examined to date, and to the authors' knowledge, there is no available data on the level of dental trauma experienced by this group.
Materials and method: The authors approached six different grappling schools, as well as leaving an invite on a grappling event page for volunteers to fill out a short survey.
Results: Around 81 respondents took part in the survey, with nearly 25% reporting that they never wore a mouthguard during grappling, and less than 50% not wearing a mouthguard all the time. Sixty-three percent of respondents had either seen dental and peri-oral injuries, or had experienced dental injuries as a result of grappling.
Conclusion: More work is needed to investigate whether mouthguards have a positive effect on the dental injury experience, and to establish the percentage of grapplers who at some point will be affected by dental trauma.

Will Weekly Win for Taxol in the UK: Comparison of Outcomes in Metastatic and locally advanced breast cancer with weekly vs. 3 weekly administration of paclitaxel: A randomised two-arm, prospective, multi-centre, open-label phase III trial comparing the activity and safety of a weekly versus a three-weekly paclitaxel treatment schedule in patients with advanced or metastatic breast cancer (2019)

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Type of publication:
Randomised controlled trial

Author(s):
Cameron, D. and Verrill, M.

35 patients from Shrewsbury and Telford Hospital NHS Trust were involved in this trial.

Citation:
Unpublished final report

Abstract:
Background: Paclitaxel has significant anti-tumour activity in patients with metastatic breast cancer who either relapse after, or are resistant, to anthracycline based treatment. In this setting, paclitaxel was routinely given as a 3-hour IV infusion at a dose of 175 mg/m2 every 3 weeks. With the aim of optimising dose and schedule of paclitaxel for patients with metastatic breast cancer, a weekly, dose-dense regimen was developed and used in various settings.
Patients and Methods: A total of 569 patients were recruited into the trial – the first and last patients were randomised on 16 September 2002 and 31 July 2006 respectively. The 2 arms were well balanced for sites of metastases, extent of prior radiotherapy and chemotherapy. The median follow up at May 2012 (when the final analysis was performed) was 94 months = 7 years, 10 months.
Results: Response rates for the weekly regimen were significantly higher than the 3-weekly arm (chi-squared test of association: p = 0.002; responses were weekly CR 3.2%, PR 18.3% vs. 3-weekly CR 1.7% and PR 11.3%). There was no significant difference in either time to progression (log rank test: p = 0.127) or overall survival (log rank test: p = 0.193) between the 2 arms.
Conclusions: In this randomised controlled trial of best scheduling, weekly paclitaxel showed a statistically higher objective response activity compared to 3-weekly schedule but no survival benefit was seen.

Evaluating the Trade-offs Men with Localised Prostate Cancer Make Between the Risks and Benefits of Treatments: The COMPARE Study (2020)

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Type of publication:
Journal article

Author(s):
Watson V, McCartan N, Krucien N, Abu V, Ikenwilo D, Emberton M, Ahmed HU

Study involved patients at Shrewsbury and Telford Hospital NHS Trust

Citation:
Journal of Urology. 2020 Aug;204(2):273-280

Abstract:
PURPOSE: COMPARE (COMparing treatment options for ProstAte cancer) aimed to evaluate and quantify the trade-offs patients make between different aspects of active surveillance and definitive therapy.
METHODS: A Discrete Choice Experiment (DCE) tool was used to elicit patients' preferences for different treatment characteristics in 34 urology departments. Patients with localised prostate cancer completed the DCE within one week of being diagnosed and before they made treatment decisions. The DCE was pre-tested (N=5) and piloted (n=106) with patients. Patients chose their preferred treatment profile based on six characteristics: treatment type (active surveillance, focal therapy, radical therapy), return to normal activities, erectile function, urinary function, not needing more cancer treatment and 10-15 year cancer-specific survival. Different tools were designed for low-intermediate (n=468) and high-risk (n=166) patients. An error-components conditional logit model was used to estimate preferences and trade-offs between treatment characteristics.
RESULTS:Low-intermediate risk patients were willing to trade 6.99% absolute decrease in survival to have active surveillance over definitive therapy. They were willing to trade 0.75%, 0.46% and 0.19% absolute decrease in survival for a one-month reduction in time-to-return to normal activities, and 1% absolute improvements in urinary and sexual function, respectively. High-risk patients were willing to trade 3.10%, 1.04% and 0.41% absolute decrease in survival for a one-month reduction in time-to-return to normal activities and 1% absolute improvements in urinary and sexual function, respectively.
CONCLUSIONS: Patients with low-intermediate risk prostate cancer preferred active surveillance to definitive therapy. Patients of all risks were willing to trade-off cancer-specific survival for improved quality-of-life.Registration:clinicaltrials.gov Registration Identifier NCT01177865Funding:Medical Research Council (UK) (grant reference: G1002509)

Non-tuberculous mycobacteria (NTM): A review of local prevalence and management of pulmonary NTM (2019)

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Type of publication:
Conference abstract

Author(s):
*Ibrahim J.; *Ali A.; *Mahmoud M.; *Hamze H.; *Crawford E.; *Makan A.; *Srinivasan K.; *Moudgil H.; *Ahmad N.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2019; vol. 199 (no. 9)

Abstract:
Introduction Prevalence of NTM varies worldwide. Guidelines for the diagnosis and management of Pulmonary NTM have been published recently and in light of this; we aimed to look at our local data of NTM isolates with particular attention to the pulmonary isolates. Methods Patient details were obtained for all positive NTM isolates from 2002 to 2017. Further details on microbiology, radiology and treatment of these patients were searched from clinical portal, Patient archives communication system for radiology and outpatient clinic letters. Results 147 NTM were isolated from pulmonary and extra pulmonary sites (figure 1). This included 53% (n=78) female patients with a mean age (SD) of 62 (21) years. 90 pulmonary isolates were considered for further analysis. 33/90 (37%) received treatment with >=3 drugs (n = 19), <=2 drugs (n = 13) and data unavailable for one patient. Where data on duration of treatment was available (n = 30), 19/30 (63%) were treated for >=18 months and 11 (37%) treated for <18 months. With reference to current guidelines [1][2], 25/90 met microbiological and radiological criteria for treatment, 15/25 (60%) were treated, 8 (32%) not treated and no data on treatment available for the remaining 2 (8%). NTM types treated include Mycobacterium Avium Complex (MAC) (n=18), M.Malmonse (n=6), M.Kansasii (n=4), M.Szulgai (n=2), M.Abscessus (n=1), M.Gordonae (n=1), M.Xenopi (n=1). 78/90 (87%) patients had underlying lung disease. Of these most common were COPD (27), bronchiectasis (27), Asthma (13), Aspergillus infection/sensitization (7), Cystic Fibrosis (3) and previous TB (3). Conclusion Our local data prior to the publishing of current guidelines shows 40% couldn't be treated for NTM disease. This may be due to the challenges of age at diagnosis, risk of side effects, difficulty in differentiation between colonised or pathological isolate; looking ahead, the current guidance may enable a more standardised approach towards diagnosis and management.

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Uptake of influenza vaccination as a preventive health care strategy (2019)

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Type of publication:
Conference abstract

Author(s):
*Ibrahim J.; *Ali J.; *Ali A.; *Makan A.; *Crawford E.; *Ahmad N.; *Srinivasan K.; *Moudgil H.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2019; vol. 199 (no. 9)

Abstract:
Introduction: Whether our local Health Care Economy is adequately prepared with uptake of targeted preventative strategies of seasonal influenza vaccination for the consequential burden on secondary health care is poorly documented. Auditing patients admitted acutely through our Acute Medical Unit, objectives were to (1) provide a point prevalence measure to the uptake of influenza vaccine among patients stratified by at risk groups, and (2) document reasons for nonadherence to current recommendations. Method(s): Auditing on three alternate days during one week in January 2018 coinciding with peak season for influenza, adult patients (>16yrs) acutely admitted were categorized and individually questioned using National Institute for Health and Care Excellence (NICE) guidelines for "immunization against Seasonal Influenza" as a benchmark identifying targeted strategies by clinical risk grouping: Group A was based on age years, and Group B on those below this age but with defined clinical risks. Comparative but surrogate standards for the groups were adopted from World Health Organization (WHO) targets and from Public Health England for uptake achievements by patients under local General Practitioners (GPs) in the West Midlands (WM) region. This audit did not consider the impact of vaccination on illness. Result(s): 120/136 (88.2%) admitted patients were audited; of these 75/120 (62.5%) had been vaccinated. Comparisons with standards adopted are shown in figure 1. Featured among 37.5% not vaccinated were GP appointments (60%), allergy (24%), low risk (9%) and mis-trust (7%). At risk groups were chronic respiratory (32%), cardiac (19%), neurological (14%) disease and diabetes (12%), cancer (7%), and others (16%). Conclusion(s): Among those admitted to secondary care, local Health Care Economy (figure 1) fall short of adopted standards from the WHO and regionally for WM region for Group A but with better figures for Group B comparing regionally, and (2) identify access at local GPs as among primary reasons for non-uptake of vaccination. (Figure Presented).

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Investigating sleep disorders: Are we able to target the right population? (2019)

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Type of publication:
Conference abstract

Author(s):
*Ibrahim J.; *Ali A.; *Khan M.Z.; *Radzali M.; *Crawford E.; *Makan A.; *Ahmad N.; *Srinivasan K.; *Moudgil H.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2019; vol. 199 (no. 9)

Abstract:
INTRODUCTION: With an increase in referrals to investigate sleep disordered breathing it is important to ensure appropriate targeted investigation. Our traditional use of the Epworth Sleepiness Scores (ESS) in screening and/or guiding treatment for obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is at best based on equivocal and sometimes conflicting published evidence. In evaluating our practice, our objectives presently were (1) to profile our patients and nature of their disease, and (2) to assess the role of Epworth scores in investigating these patients. METHOD(S): Retrospective review of 200 successive adults referred to this department over an 18 month period to end December 2017. Data were extracted from medical records and analysed using SPSS statistics packages appropriately for normal and nonparametric distribution with statistically significant findings reported at p<0.05. RESULT(S): Mean (SD, range) age of patients was 53.2 (13.8, 22 to 84) years with 55% males. Comparing those diagnosed with (n=152) to those without OSAHS (n=48), patients with disease tended to be older at 54.7 (13.3, 24-85) versus 48.5 (14.7, 22-79) years, had higher BMI at 36.8 (8.7, 21.5- 69.4) versus 32.6(8.5, 19.5-51.9) kg/m2 with more positively diagnosed from the males investigated (92/111 versus 60/89). Markers of disease severity were as expected with higher levels among those diagnosed with disease: Apnoea Hypopnoea Index (AHI) 25 versus 2.3, Oxygen desaturation Index (ODI) (at 4%) 25.9 versus 2.3, and time spent with oxygen saturation below 90% at 25.9 versus 8.3%. The ESS (n=121) did not differ between groups, respectively 11.3 (5.9, 0-24) versus 12.4 (6.2, 0-24), p=0.395 (not significant). Findings were similar analysed by stepwise logistic regression. None of the markers of disease severity correlated with ESS (Spearman rho= -0.04, p=0.675, NS). CONCLUSION(S): The relatively high (76%) prevalence of disease in these patients investigated suggests appropriately targeted investigation; whereas findings related to increasing age, male gender, and increased BMI are as expected, the distribution of the ESS again does not show the ability to discriminate and conversely had found relatively over-reporting of symptoms among those without disease and under-reporting of those with disease but not at statistically significant levels.

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Follow up chest radiograph in community acquired pneumonia (CAP)-are we meeting the standards? (2019)

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Type of publication:
Conference abstract

Author(s):
*Zeb M.S.; *Hamze H.; *Ali A.; *Annabel M.; *Ahmad N.; *Moudgil H.; *Ibrahim J.; *Srinivasan K.S.; *Crawford E.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2019; vol. 199 (no. 9)

Abstract:
Introduction and objectives CAP accounts for 29,000 deaths per annum in the UK with In-patient mortality of 17.7% [1]. In older population (>65years) associated malignancy is 9.1%. Current guidelines [2] recommend chest radiograph (CXR) follow up 6 weeks after CAP in high risk patients. We aimed to audit our follow up practice with a view to service improvement for early detection of malignancy and complications from CAP. Methods Patients were identified via retrospective review of local database of patients recorded as "CAP" on discharge from 02/01/2017 to 01/31/2018. CXR reports were reviewed using patient archives communication system for radiology and clinical portal. Results 97 patients were identified with discharge diagnoses recorded as "CAP". We excluded patients below 50 years of age (n=7), those without radiographic pneumonia (n= 26), CXR not reported (as patient deceased) (n=2) and patients with CAP who died within 6 weeks of presentation (n=25, mean age 83 years; this included inpatients as well as those died post discharge from hospital). Patients included (n=37). Mean age 74 years. Female patients (n=19, 50.1%). 14 (37.8%) patients had follow up CXR. One of these showed incomplete resolution with no further follow up or investigation arranged. Three patients were considered not suitable for follow up in view of their co-morbidities. 20/37 (58%) patients didn't have appropriate follow up arranged. Conclusion(s): Our results underestimated CAP incidence at secondary level based on the discharge diagnosis of CAP. Mortality in this cohort was high signifying the severity of pneumonia, particularly with increasing age. There was one unresolved consolidation with no lung cancers diagnosed implying small sample size as a limitation in our study. Nevertheless 26 (27%) of patients had clinical diagnosis of CAP with no radiographic evidence. There was heterogeneity in the follow up CXR arrangements with patients shared between hospital specialists and primary care. For improvement we need to ensure appropriate follow up CXR (streamlined by staff education), radiology reports (highlighting the need for repeat CXR) and virtual clinics are arranged.

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