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Impact of COVID-19 on patients with chronic lung disease (2021)

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Type of publication:Conference abstract

Author(s):*Etel E.; *Chapman T.; *Moudgil H.; *Srinivasan K.; *Makan A.; *Crawford E.; *Ahmad N.

Citation:European Respiratory Journal 2021; 58: Suppl. 65, PA3265.

Abstract:Background: Patients with chronic lung disease especially Asthma and/or Chronic Obstructive Pulmonary Disease (COPD) are at an increased risk of acquiring COVID-19. Hence, these patients have been asked to shield in the United Kingdom (UK) during the pandemic.
Aims: Our objective was to look at the severity of COVID and in-hospital mortality, in patients that had COPD and/or Asthma and were admitted to our rural district general hospital with a positive PCR for SARS-CoV2.
Method: We carried out a retrospective analysis from the 3rd and 4th week of January 2021, on patients in our hospital with COVID-19 and COPD and/or Asthma. The severity of COVID was defined by their need for O2+ devices (Non-invasive ventilation in the form of BiPAP, CPAP or CPAP HOOD and High flow nasal cannula). We used MS Excel for data analysis.
Results: 247 patients were in hospital, 52% males(n=129) with a mean age(SD) 73 (14.7) years. We excluded 127 who tested negative for SARS-CoV2 and then a further 92 who had tested positive for SARS-CoV2 but did not have COPD and/or Asthma.
In total, 28 patients were included in the study. 79% males(n=22). Mean age(SD) 75 (11.5) years. 29(n=8) had severe disease and needed treatment with O2+ device. Of these, 50%(n=4) died during admission. Overall unadjusted mortality was 25%(n=7) and these patients had on an average 3 comorbidities with a mean age(SD) of 80 (14) years.
Conclusion: Retrospective analysis in our cohort of COVID-19 patients’ showed 23% have underlying COPD and/or Asthma and within this group
1) 1 in 3 patients will have severe disease needing O2+ treatment
2) 1 in 4 patients will die
3) Mean Age of 80 years and ≥ 3 comorbidities will carry a poor prognosis.

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Managing COVID-19 illness: chest radiographs support defining both prognosis and follow up (2021)

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Type of publication:Conference abstract

Author(s):*Etel E.; *Chapman T.; *Moudgil H.; *Srinivasan K.; *Makan A.; *Crawford E.; *Ahmad N.;

Citation:European Respiratory Journal 2021; 58: Suppl. 65, PA459

Abstract:Introduction: Chest radiology is pivotal managing acute COVID-19 illness but potentially equally important to follow up. Objectives of this study were to (1) quantify those with COVID requiring follow up, (2) investigate how findings relate to severity, and (3) report abnormal radiology at follow up estimating continued demands.
Methods: Retrospective analysis of 217 patients, mean age 71.8 (SD 8.7, range 29-87) years, admitted March to May 2020 and subsequently tracked. Patients requiring >40% FiO2, and/or respiratory device support had severe disease and CXRs were normal or abnormal to COVID changes. Data analysed using statistical software reporting comparisons by chi square (X2).
Results: Initial CXRs for 123/213 (58%) patients were abnormal; 59/153 (39%) surviving admission attended follow up; others defaulted or were not requested with normal CXR or expected poor prognosis. 39 (66%) CXRs improved, 20 (34%) remained abnormal; of these, 9 patients had chest CT scans. Severe disease contributed to higher mortality, respectively 37/58 (64%) versus 46/159 (29%), X2 (df 1, n=217) 21.87, p=.0001. Comparing abnormal with normal CXR, 47/122 (39%) versus 11/91 (12%) had severe disease, X2 (df 1, n=213) 18.38, p=.000018. 55/123 (45%) versus 28/90 (31%) of those with initial abnormal CXR have since died, X2 (df 1, n=213) 4.04, p=.0044.
Conclusions: Mortality is associated with both the severity of illness and initial COVID related abnormal CXR; 58% have such changes at presentation and among the survivors having follow up radiology improves in two-thirds with approximately half the others then investigated by chest CT giving some indication to planning future services.

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Blood lactate level in patients with severe COVID-19: Does it have any added value? (2021)

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Type of publication:Conference abstract

Author(s):*Hassan R.; *Moudgil H.; *Crawford E.J.; *Makan A.; *Srinivasan S.; *Ahmad N.

Citation:European Respiratory Journal 2021; 58: Suppl. 65, PA3472.

Abstract:Background: Increased blood lactate (BLac) concentration is common in critically ill patients. They are measured to estimate disease severity, predict morbidity and mortality. A level >2mmol/L is an outcome predictor in Septicaemia. COVID-19 mimics features of Sepsis with reports suggesting that BLac would be of added benefit in predicting survivorship in patients with COVID-19.
Aims: We set out to validate the role of BLac levels in our cohort of RT-PCR+ severe COVID-19 patients admitted to the respiratory support unit (RSU) of a district general hospital in United Kingdom (UK)
Methods: We carried out a retrospective analysis of all patients admitted to the RSU with features of severe COVID-19 as set out by the World Health Organisation (5). Data was collected for the 2 months of November and December 2020. We used Microsoft Excel for analysis and vassar stats for statistical evaluation
Results: 60 patients were admitted to RSU in the time period. 60% males (n=36) with a Mean age (SD) 69.5 (13.6) years
Mean (SD) BLac measured in all patients was 1.5 (0.42) mmol/L. 17% (n=10) patients had BLac between 2 mmol/L to 2.5 mmol/L, of which 2 patients have died. Blac level in patients with Age>65 years (n=38) was < 2.0 mmol/L; Mean (SD) 1.49 mmol/L (0.42). Overall, 9 patients died during this period with Mean (SD) BLac of survivors 1.51 mmol/L (0.4) v non-survivors 1.47 mmol/L (0.54) (p=0.4)
Conclusion: Analysis of our small cohort of severe COVID-19 patients’ show
1) Despite having features of Sepsis, Blac is below the critical threshold of 2mmol/L for majority of the patients
2) Blac >2mmol/L did not predict increased mortality and there was no significant difference in the Mean Blac between survivors and non survivors

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Hospital re-admissions and deaths associated with COVID-19 illness: survival analysis (2021)

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Type of publication:Conference abstract

Author(s):*Ali Z.; *Ahmed S.; *Makan A.; *Crawford E.; *Srinivasan K.; *Dev D.; *Ahmad N.; *Moudgil H.

Citation:European Respiratory Journal 2021; 58: Suppl. 65, OA4194

Abstract:Introduction: With better than anticipated survival (73.5%) of patients admitted with COVID-19 (SARS-Cov-2 RNA) at this hospital concern is whether this is linked to higher re-admission rates or later deaths. Relating to initial severity, objectives were to (1) analyse survival during follow up, and (2) document pattern of re-admissions.
Methods: Retrospective analysis of 217 patients, mean age 71.8 (SD 8.7, range 29-87) years admitted with COVID-19 during the 2020 UK peak and surge. Patients requiring >40% FiO2 demand or oxygen plus devices had severe illness. CXR were abnormal if with COVID changes. Analysis using statistical software reports Kaplan Meier survival curves with log rank tests and comparisons by chi square (X2).
Results: Deaths climbed from 60/217 (27.6%) at discharge to 83/217 (38.2%) during follow up >250 days. Figure below shows survival curves based on initial severity; separation of curves highlights worse trajectory with severe disease [X2 (df 1, n=213) 29.42 p=.0000058]. Similar curves were noted in patients with abnormal (58%) initial CXRs [X2 (df 1, n=213) 5.53, p=.019]. 51/157 (32.5%) surviving initial admission were re-admitted with an early date skew of re-admissions.
Conclusions: Data confirm the trend in deaths after discharge and high re-admissions early after discharge. Survival is predicted by severity of respiratory dependency and CXR COVID changes.

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Is there an endotype to the treatable eosinophilic trait of chronic obstructive pulmonary disease (COPD) (2021)

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Type of publication:Conference abstract

Author(s):*Walsh O.; *Marathe M.; *Moudgil H.; *Srinivasan K.; *Crawford E.; *Makan A.; *Ahmad, N.

Citation:European Respiratory Journal 2021; 58: Suppl. 65, PA3425.

Abstract:Introduction: There has been much interest in defining phenotypes in COPD particularly in relation to eosinophils and whether it is a treatable trait. Augusti el al (1) have suggested defining an endotype of COPD and moving away from clinical measures, when it comes to offering treatment. An endotype in eosinophilic COPD remains to be explored. Our main aim was to define an endotype for the treatable eosinophilic trait of COPD particularly focusing on the Body Mass Index (BMI), as previous reports have shown this trait may have a BMI>=25 kg/m2(2). Methods and Aims: A retrospective analysis was done reviewing the results of all COPD patients with an FEV1: FVC ratio <0.7, discussed at the local Multi-disciplinary Team meeting in 2019 and 2020. We excluded patients with Asthma and Overlap syndrome. Serum eosinophil levels over the past 3 years and BMI were obtained from the local electronic portal and MDT pro forma. We compared highest 3 year eosinophil counts (EC) in those with BMI < and >=25 kg/m2. We used MS Excel and Vassar stats for statistical calculations. <br/>Result(s): 168 patients were reviewed of which 24 patients were excluded based on the inclusion criteria, leaving 144 patients for analysis. The mean age (SD) was 57 (6.8) years. 58% (n= 84) were males. 39% (n=56) patients had BMI<25 kg/m2 (Group A) and 61% (n=88) patients had BMI>=25 kg/m2 (Group B). Mean (SD) of EC was 0.16×109/L (0.08) in Group A v Mean (SD) of EC 0.34 x109/L (0.14) in Group B [95% CI 0.14-0.21; p < 0.0001]. Our data show that patients with a BMI>=25 kg/m2 is an endotype of COPD patients who have EC>0.2 x109/L. Further research into this endotype and targeted treatments for eosinophilic COPD needs to be carried out.

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Holt-Oram Syndrome: An Incidental Diagnosis (2022)

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Type of publication:Journal article

Author(s):*Gupta M; *Dosu A; *Makan J

Citation:Cureus, 2022 May 11; Vol. 14 (5), pp. e24899

Abstract:Holt-Oram syndrome is a rare autosomal dominant disorder which occurs because of mutations in the TBX5 genes. Most notable manifestations include musculoskeletal deformities, predominantly affecting the upper limbs, and congenital heart defects. Presentation could be multifaceted leading to delay in diagnosis. We describe an interesting incidental diagnosis of Holt-Oram syndrome in a young female adult who accompanied her son to the clinic. He had undergone closure of both atrial septal defect (ASD) and patent ductus arteriosus (PDA) in his infancy. She reported progressive exertional dyspnoea, reduced exercise tolerance, and palpitations; incidentally, she was noted to have right upper limb deformities. These findings prompted further evaluation and thereafter, resulted in a diagnosis of Holt-Oram syndrome.

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Comparison of multiple gene expression platforms for measuring a bladder cancer hypoxia signature (2022)

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Type of publication:
Journal article

Author(s):
Smith TAD; Lane B; More E; Valentine H; Lunj S; Abdelkarem OA; Irlam-Jones J; Shabbir R; Vora S; *Denley H; Reeves KJ; Hoskin PJ; Choudhury A; West CML

Citation:
Molecular Medicine Reports, 2022 Aug; Vol. 26 (2)

Abstract:
Tumour hypoxia status provides prognostic information and predicts response to hypoxia modifying treatments. A previous study by our group derived a 24 gene signature to assess hypoxia in bladder cancer. The objectives of the present study were to compare platforms for generating signature scores, identify cut off values for prospective studies, assess intra tumour heterogeneity and confirm hypoxia relevance. Briefly, RNA was extracted from prospectively collected diagnostic biopsies of muscle invasive bladder cancer (51 patients), and gene expression was measured using customised Taqman Low Density Array (TLDA) cards, NanoString and Clariom S arrays. Cross platform transferability of the gene signature was assessed using regression and concordance analysis. The cut off values were the cohort median expression values. Intra and inter tumour variability were determined in a retrospective patient cohort (n=51) with multiple blocks (2 18) from the same tumour. To demonstrate relevance, bladder cancer cell lines were exposed to hypoxia (0.1% oxygen, 24 h), and extracted RNA was run on custom TLDA cards. Hypoxia scores (HS) values showed good agreement between platforms: Clariom S vs. TLDA (r=0.72, P<0.0001; concordance 73%); Clariom S vs. NanoString (r=0.84, P<0.0001; 78%); TLDA vs. NanoString (r=0.80, P<0.0001; 78%). Cut off values were 0.047 (TLDA), 7.328 (NanoString) and 6.667 (Clariom S). Intra tumour heterogeneity in gene expression and HS (coefficient of variation 3.9%) was less than inter tumour (7.9%) variability. HS values were higher in bladder cancer cells exposed to hypoxia compared with normoxia (P<0.02). In conclusion, the present study revealed that application of the 24 gene bladder cancer hypoxia signature was platform agnostic, cut off values determined prospectively can be used in a clinical trial, intra tumour heterogeneity was low and the signature was sensitive to changes in oxygen levels in vitro.

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Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial (2022)

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Type of publication:
Randomised controlled trial

Author(s):
Parker CC; James ND; Brawley CD; Clarke NW; Ali A; Amos CL; Attard G; Chowdhury S; Cook A; Cross W; Dearnaley DP; Douis H; Gilbert DC; Gilson C; Gillessen S; Hoyle A; Jones RJ; Langley RE; Malik ZI; Mason MD; Matheson D; Millman R; Rauchenberger M; Rush H; Russell JM; Sweeney H; Bahl A; Birtle A; Capaldi L; Din O; Ford D; Gale J; Henry A; Hoskin P; Kagzi M; Lydon A; O'Sullivan JM; Paisey SA; Parikh O; Pudney D; Ramani V; Robson P; *Srihari NN; Tanguay J; Parmar MKB; Sydes MR; STAMPEDE Trial Collaborative Group

Citation:
PLoS Medicine, 2022 Jun 07; Vol. 19 (6), pp. e1003998

Abstract:
Background: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).Methods and Findings: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.Conclusions: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.Trial Registration: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

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Effectiveness of a web-based virtual journal club to promote medical education (Web-Ed): protocol of a multicentre pragmatic randomised trial (2022)

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Type of publication:Randomised controlled trial

Author(s):Michael Rimmer, Nagla Elfaki, Cheryl Dunlop, Damien Coleburt, Neil Cowan, Olivia Raglan, Jhia Jiat Teh, Maria Fisher, Sarah Mcrobbie, Nilaani Murugesu, Meera Ramcharn, Mohamed Abdelrahman, *Yazid Jibrel, *Matthew Wood, *William Parry-Smith, Bassel H Al Wattar

Citation:BMJ Open, 2022 Vol.12, Issue 6

Abstract:Introduction: A journal club (JC) is a commonly used medical educational tool. Videoconferencing technology can facilitate the delivery of JCs, however, there remains no evidence on the role of web-based virtual JCs in promoting the acquisition and retention of medical knowledge. The Web-Ed trial aims to evaluate the educational benefits, feasibility and acceptability of web-based virtual JCs compared with traditional face-to-face ones.

Methods and analysis: Web-Ed is a multicentre pragmatic parallel-group randomised trial across teaching hospitals within the UK National Health Service (NHS). We will enrol qualified doctors or medical students who are >18 years old, proficient in English and able to use online videoconferencing software. Block randomisation will be used to allocate participants in 1:1 ratio to either intervention group. Both groups will be presented with the same educational material and follow a standardised JC structure hosted by nominated moderators and medical faculty members.

The primary outcome is the difference in participants’ knowledge acquisition and retention 7 days after the JCs evaluated using standardised multiple-choice questions. We will report secondarily on the feasibility and acceptability of the JCs using Likert scale questionnaires. Assuming a 30% drop-out rate, we aim to enrol 75 participants to detect a 20% improvement in knowledge acquisition at 80% power and 5% significance. We will report using mean difference or risk ratio with 95% CIs and assess significance using parametric/non-parametric testing. Where relevant, we will adjust for predetermined characteristics (age, grade of training and session duration) using multivariate regression analyses.

Ethics and dissemination: Web-Ed was designed by doctors in training to address their learning needs and evaluate the preferred mode of learning. The trial results will be published in peer-reviewed journals and presented at relevant scientific conferences. The trial has been approved by the NHS Health Regulation Authority (21/HRA/3361).

Trial registration number: ISRCTN18036769.

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