Staff Publication

Is it useful to analyse all waste material obtained during endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA)? (2019)

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Type of publication:
Poster presentation

Author(s):
*V. Tharmarajah, *H. Hope, *E. Cobby, J. *Stafford, *R. Heinink

Citation:
European Respiratory Journal 2019 Vol. 54, Suppl 63, PA3064

Abstract:
Background: It is not standard practice to always analyse waste material obtained from EBUS in addition to the samples taken from the EBUS-TBNA needle.
Method: A retrospective review of EBUS carried out between 1/1/17 and 16/3/18 was performed. We collected data where samples were taken both via the EBUS-TBNA needle and from waste material from the same node. It was also noted as to which sample contained the most diagnostic material.
Results: 54 EBUSs were performed within the study period. If the waste obtained from both the flushing of the EBUS-TBNA needle and from the flushing of the suction syringe contained anything but clear fluid, the waste was sent to cytology, paired with the EBUS-TBNA needle sample from the same node. 38 patients had samples taken from both waste material and via the EBUS-TBNA needle (47 nodes in total). Malignancy was seen in 26 nodes, granulomata in 9, and no disease seen in 12 (1 insufficient sample, 10 true negatives and 1 false negative). Of the 27 malignant nodes, the EBUS-TBNA needle sample contained diagnostic material in 25 samples (sensitivity 96%). The waste sample contained diagnostic material in 23 samples (sensitivity 85%); in 13 of these, the waste sample was felt to have either as much or more diagnostic material than the sample obtained from the EBUS-TBNA needle.
Conclusion: Waste material obtained during EBUS contains diagnostic material in the majority of cases, and in our cohort contained at least as much material as the corresponding EBUS-TBNA needle sample in 50% of samples. This is important when considering the rising amount of tissue required by oncologists for molecular testing.

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Levothyroxine to increase live births in euthyroid women with thyroid antibodies trying to conceive: the TABLET RCT (2019)

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Type of publication:
Journal article

Author(s):
Dhillon-Smith R K, Middleton L J, Sunner K K, Cheed V, Baker K, Farrell-Carver S, Bender-Atik R, Agrawal R, Bhatia K, Edi-Osagie E, Ghobara T, Gupta P, Jurkovic D, Khalaf Y, MacLean M, McCabe C, Mulbagal K, Nunes N, Overton C, Quenby S, Rai R, Raine-Fenning N, Robinson L, Ross J, Sizer A, Small R, Tan A, *Underwood M , Kilby M D, Boelaert K, Daniels J, Thangaratinam S, Chan S,  Coomarasamy A.

Citation:
Efficacy and Mechanism Evaluation; Volume: 6, Issue: 11, October 2019

Abstract:
Background: Thyroid autoantibodies, specifically thyroid peroxidase antibodies, have been associated with miscarriage and pre-term birth in women with a normal thyroid function. Small randomised controlled trials have found that treatment with levothyroxine may reduce such adverse outcomes in pregnancy.
Objectives: The Thyroid AntiBodies and LEvoThyroxine (TABLET) trial was conducted to explore the effects of levothyroxine in euthyroid women with thyroid peroxidase antibodies. A concurrent mechanistic study was conducted to examine the effect of levothyroxine on immune responses.
Design: This was a randomised, double-blind, placebo-controlled, multicentre study.
Setting: The TABLET trial was conducted in 49 hospitals across the UK between 2011 and 2016.
Participants: Euthyroid women who tested positive for thyroid peroxidase antibodies, were aged between 16 and 41 years and were trying to conceive either naturally or through assisted conception were eligible.
Intervention: Participants were randomised to levothyroxine at a dose of 50 µg daily or placebo. The intervention was commenced preconception and continued until the end of a pregnancy. Women were given a 12-month period to conceive from randomisation.
Main outcome measures: The primary outcome was live birth at ≥ 34 completed weeks of gestation. The secondary outcomes included miscarriage at < 24 weeks; clinical pregnancy at 7 weeks; ongoing pregnancy at 12 weeks; gestation at delivery; birthweight; appearance, pulse, grimace, activity and respiration (Apgar) scores; congenital abnormalities; and neonatal survival at 28 days of life.
Methods: Participants were randomised in a 1 : 1 ratio. Minimisation was implemented for age (< 35 or ≥ 35 years), number of previous miscarriages (0, 1 or 2, ≥ 3), infertility treatment (yes/no) and baseline thyroid-stimulating hormone concentration (≤ 2.5 or > 2.5 mlU/l) to achieve balanced trial arms. Women were followed up every 3 months while trying to conceive to check thyroid function and general well-being, and, once pregnant, were seen each trimester: 6–8 weeks, 16–18 weeks and 28 weeks. Any abnormal thyroid results were managed in line with clinical guidance at the time.
Results: Of the 19,556 women screened, 1420 women were eligible and 952 were randomised to receive levothyroxine (n = 476) or placebo (n = 476). Six women from each arm either were lost to follow-up or withdrew from the trial. A total 540 women became pregnant: 266 in the levothyroxine arm and 274 in the placebo arm. The live birth rate was 37% (176/470) in the levothyroxine group and 38% (178/470) in the placebo group, translating to a relative risk of 0.97 (95% confidence interval 0.83 to 1.14; p = 0.74) and an absolute risk difference of –0.4% (95% confidence interval –6.6% to 5.8%). A subset of 49 trial participants (26 in the levothyroxine arm and 23 in the placebo arm) were recruited to assess changes in their serum chemocytokine concentrations. Treatment with levothyroxine resulted in some changes in chemocytokine concentrations in the non-pregnant state and in early pregnancy, but these had no association with clinical outcome.
Conclusions: Levothyroxine therapy in a dose of 50 µg per day does not improve live birth rate in euthyroid women with thyroid peroxidase antibodies.
Limitations: Titration of the levothyroxine dose based on thyroid-stimulating hormone/thyroid peroxidase concentrations was not explored.
Future work: Future research could explore the efficacy of levothyroxine administered for the treatment of subclinical hypothyroidism.
Trial registration: Current Controlled Trials ISRCTN15948785 and EudraCT 2011-000719-19.
Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

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The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM Trial (2020)

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Type of publication:
Journal article

Author(s):
CB Okeke Ogwulu, I Goranitis, AJ Devall, V Cheed, ID Gallos, LJ Middleton, HM Harb, HM Williams, A Eapen, JP Daniels, A Ahmed, R Bender‐Atik, K Bhatia, C Bottomley, J Brewin, M Choudhary, S Deb, WC Duncan, AK Ewer, K Hinshaw, T Holland, F Izzat, J Johns, M Lumsden, P Manda, JE Norman, N Nunes, CE Overton, K Kriedt, S Quenby, S Rao, J Ross, A Shahid, *M Underwood , N Vaithilingham, L Watkins, C Wykes, AW Horne, D Jurkovic, A Coomarasamy, TE Roberts

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; May 2020; Vol 127 (no. 6); p. 757-767

Abstract:
Objectives: To assess the cost‐effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding.
Design: Economic evaluation alongside a large multi‐centre randomised placebo‐controlled trial.
Setting: Forty‐eight UK NHS early pregnancy units.
Population: Four thousand one hundred and fifty‐three women aged 16–39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac.
Methods: An incremental cost‐effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages.
Main outcome measures: Cost per additional live birth at ≥34 weeks of gestation.
Results: Progesterone intervention led to an effect difference of 0.022 (95% CI −0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI −£559 to £711) more than the mean cost in the placebo group. The incremental cost‐effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014–0.096) and this was associated with a cost saving of £322 (95% CI −£1318 to £673).
Conclusions: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost‐effective intervention, particularly for women with previous miscarriage(s).

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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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