2019

Cellular response to influenza infection: Lymphopenia and a reduced lymphocyte/monocyte ratio (2019)

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Type of publication:
Conference abstract

Author(s):
*Abdulsamad S.P.; *Bhatia K.; *Khalid H.; *Makan A.; *Crawford E.; *Ahmad N.; *Srinivasan K.; *Moudgil H.

Citation:
European Respiratory Journal; Sep 2019; vol. 54, PA2383

Abstract:
Objectives: Provisional work has proposed a diagnostic role investigating cellular responses in acute viral respiratory pathology. Analysing patients with influenza(flu), objectives were(1)to assess magnitude of lymphocyte and monocyte responses in acute infection and(2)report on the potential benefit if detecting lymphopenia and a reduced lymphocyte to monocyte ratio(LMR)
Methods: Retrospective analysis of all adults with flu admitted to this trust during winter season 2016/7. Computer records provided differential white cell counts as relative(%of total white cell counts, WCC)and absolute counts for lymphocytes(normal range 1-4×109)and monocytes(0.1-0.9×109);analysis was with SPSS
Results: 143(54% female)adults(142 Flu A [H3N2]and 1 Flu B)were admitted. Mean age was 70.3(SD 19.4, range 20-98)years. Flu was primary diagnosis for 53(37%);43/90(48%) remaining also had a respiratory presentation. Lymphocyte count<20% WCC presented in 122(85%)and monocyte count >10%WCC in 43 (30%)with both markers in 35(25%). Lymphocyte counts were skewed, median 0.8(IQ 0.5-1.2)with lymphopenia at initial testing in 87(60%);among others there was a fall from admission values in 45 (31%). The lymphocyte/monocyte ratio (LMR) was <2 in 115(80%)of all presentations and specifically in 82/87(94%)with initial lymphopenia
Conclusion(s): Irrespective of whether primarily with flu or as a concurrent illness, acute lymphopenia and a LMR<2 at presentation as a measure of cellular response in admitted patients potentially presents an early and alternative strategy identifying patients with acute flu. Future work is required to establish sensitivity, specificity, negative and positive predictive values in a wider unselected similar population.

Optimizing chemotherapy for frail and/or elderly patient with advanced gastroesophageal cancer (AGOAC): the GO2 phase III trial (2019)

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Type of publication:
Conference abstract

Author(s):
Swinson D.E.; Hall P.; Seymour M.; Lord S.; Marshall H.; Ruddock S.; Cairns D.; Waters J.; Wadsley J.; Falk S.; Roy R.; Joseph M.; Nicoll J.; Vellios Kamposioras K.; Tillett T.; Cummins S.; Grumett S.; Stokes Z.; Waddell T.; *Chatterjee A.; Garcia A.; Allmark C.; Khan M.; Petty R.

Citation:
Journal of Geriatric Oncology; Nov 2019; vol. 10 (no. 6), Supplement 1, S8

Abstract:
Introduction: aGOAC patients are frequently elderly and/or frail.
Objective(s): (i) find the optimum dose of oxaliplatin capecitabine (OCap) for this population; (ii) explore the use of an objective geriatric assessment to individualize dose for maximum overall treatment utility (OTU), a composite of clinical benefit, tolerability, quality of life (QL) and patient value.
Method(s): Patients with aGOAC were eligible if there was uncertainty of the appropriate dose of chemotherapy. Baseline assessment included global QL; symptoms; functional scales; comorbidity; frailty. Randomization was 1:1:1 to dose Level A (Ox 130 mg/m2 d1, Cap 625 mg/m2 bd d1-21, q21d), B (80% Level A) or C (60% Level A). At 9 weeks, patients were scored for OTU. Non-inferiority (vs A) was assessed using PFS, censored at 12 months, with upper boundary HR 1.34 (based on patients' and clinicians' discussions), needing 284 PFS events per two-way comparison. In a separate sub-study, when there was uncertainty regarding the use of chemotherapy, patients were randomized between level C and supportive care alone (SCA).
Results and Conclusion(s): 512 patients were randomized, 2014-2017, at 61 UK centers. Age, performance status and frailty were similar in all arms. Non-inferiority of PFS is confirmed for Level B vs A (HR 1.09, CI 0.89-1.32) and for Level C vs A (HR 1.10, CI 0.90-1.33). Level C patients had the least toxicity and best OTU outcomes. When analyzed by baseline age, frailty and PS no group was identified who benefit more from higher treatment doses. A further 46 patients were randomized between chemotherapy and SCA. A non-significant trend to improved survival was observed (HR=0.69, CI 0.32-1.48) and QL deteriorated less with chemotherapy. This is the largest RCT specifically investigating frail and/or elderly aGOAC patients, and should guide future treatment. The lowest dose tested was non-inferior in terms of PFS, produced less toxicity and better overall treatment utility.

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 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.

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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