Author: Jason Curtis

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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Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation (2022)

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Type of publication:Journal article

Author(s):Grossi U; *Lacy-Colson J; Brown SR; Cross S; Eldridge S; Jordan M; Mason J; Norton C; Scott SM; Stevens N; Taheri S; Knowles CH

Citation:Techniques in Coloproctology, 2022 May 19 [epub ahead of print]

Abstract:Background: The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. Methods: The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ).Results: Of a calculated sample size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (- 1.09 [95% CI – 1.76, – 0.41], p = 0.0019, and – 0.92 [- 1.52, – 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [n = 2] or missing primary outcome [n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (- 1.38 [- 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (- 1.51 [- 2.87, – 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (- 14.3 [95% CI – 23.3, – 5.4], and – 0.92 [- 1.52, – 0.32], respectively), CC-BRQ safety behavior (- 13.7 [95% CI – 20.5, – 7.0], and – 13.0 [- 19.8, – 6.1], respectively), and BIPQ negative perceptions (- 16.3 [95% CI – 23.5, – 9.0], and – 10.5 [- 17.9, – 3.2], respectively).Conclusions: With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse. Trial Registration: ISRCTN Registry (ISRCTN11747152)

Validation of the OAKS prognostic model for acute kidney injury after gastrointestinal surgery (2022)

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Type of publication:Journal article

Author(s):STARSurg Collaborative and EuroSurg Collaborative (includes Chohan K.; Dhuna S.; Haq T.; Kirby S.; Lacy-Colson J.; Logan P.; Malik Q.; McCann J.; Mughal Z.; Sadiq S.; Sharif I.; Shingles C.; Simon A.; Chaudhury N.; Rajendran K.; Akbar Z.)

Citation:BJS Open, 2022, 6(1)

Abstract:Background: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Method(s): The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study ('IMAGINE') of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study ('Tayside') in major abdominal surgery (2011-2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Result(s): In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655-0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323-0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specificity range 0.881-0.890 (Tayside 95 per cent c.i. 0.853 to 0.905; IMAGINE 95 per cent c.i. 0.881 to 0.899). Conclusion(s): The OAKS prognostic model can identify patients who are not at high risk of postoperative AKI after gastrointestinal surgery with high specificity.

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A single faecal bile acid stool test demonstrates potential efficacy in replacing SeHCAT testing for bile acid diarrhoea in selected patients (2022)

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Type of publication:Journal article

Author(s):Kumar A; Al-Hassi HO; Jain M; Phipps O; Ford C; Gama R; Steed H; *Butterworth J; McLaughlin J; Galbraith N; Brookes MJ; Hughes LE

Citation:Scientific Reports, 2022 May 18; Vol. 12 (1), pp. 8313

Abstract:This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the 75 selenium-homotaurocholic acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn's disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (μmol/g) and interquartile ranges in patients in the control group (2.8; 1.6-4.2), BAD (3.6; 1.9-7.2) and post-cholecystectomy cohort 3.8 (2.3-6.8) were similar, but all were significantly lower (p < 0.001) compared to the Crohn's disease cohort (11.8; 10.1-16.2). FBA concentrations in patients with SeHCAT retention of < 15% (4.95; 2.6-10.5) and < 5% (9.9; 4.8-15.4) were significantly higher than those with a SeHCAT retention > 15% (2.6; 1.6-4.2); (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity using FBA cut-off of 1.6 μmol/g (using ≤ 15% SeHCAT retention as diagnostic of BAD) were 90% and 25% respectively. A single random stool sample may have potential use in diagnosing severe BAD or BAD in Crohn's patients. Larger studies are now needed to confirm the potential efficacy of this test to accurately diagnose BAD in the absence of SeHCAT testing.

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