Now showing items 1-20 of 71

    • FIT stratification in the COVID era - Is it safe for rectal bleeding?

      Seehra, Jaspreet; Bailey, James A; Chapman, Caroline J; Morling, Joanne R; Humes, David J; Banerjea, Ayan (Oxford University Press, 2021)
      Aims: Faecal Immunochemical Tests (FIT) are increasingly used for stratification of colorectal cancer risk in symptomatic patients. FIT is not currently recommended for use in patients with rectal bleeding, but recent studies have reported its safe use. We report our experiences of FIT in patients presenting with rectal bleeding during the COVID-19 pandemic. Method(s): Patients referred to NUH NHS Trust with rectal bleeding from 15/04/20-15/08/20 were invited to complete a postal-based FIT (OCSensor). Demographics, symptoms, investigations and results were recorded. Outcomes were retrospectively reviewed using an electronic hospital system. Result(s): 344 patients were invited to participate, with 301 (87.5%) returning FITs in accordance with testing protocol. 36 patients declined to be seen, 4 were considered not fit for investigation, and 4 had incomplete records. 257 patients were included in the final analysis with 10 CRC detected (3.9%). Rectal bleeding (257, 100%) was the most common presenting symptom followed by change in bowel habit (133, 51.8%). 10 CRC were diagnosed (3.9%). 2 CRC were detected with FIT 100 mug Hb / g faeces (8/45, 17.8%). FIT result was significantly associated with CRC diagnosis (p<0.0001). 4 with CRC had anaemia (4/53, 7.5%), 1 had thrombocytosis (1/12, 8.3%). Conclusion(s): FIT missed 20% of CRC in this patient group with the application of a very low threshold (<4 mug Hb / g faeces). Both cancers missed by FIT were detectable on digital rectal examination, emphasising the importance of this examination in primary care.
    • Quantitative FIT stratification is superior to NICE referral criteria NG12 in a high-risk colorectal cancer population

      Bailey, James A; Ibrahim, H; Bunce, J; Chapman, Caroline J; Morling, Joanne R; Simpson, J; Humes, David J; Banerjea, Ayan (Springer Nature, 2021)
      BACKGROUND: Guidelines for urgent investigation of colorectal cancer (CRC) are based on age and symptom-based criteria. This study aims to compare the diagnostic value of clinical features and faecal immunochemical test (FIT) results to identify those at a higher risk of CRC, thereby facilitating effective triage of patients., METHODS: We undertook a review of all patients referred for investigation of CRC at our centre between September 2016 and June 2018. Patients were identified using a prospectively recorded local database. We performed a logistic regression analysis of factors associated with a diagnosis of CRC., RESULTS: One-thousand-and-seven-hundred-eighty-four patients with FIT results were included in the study. Change in bowel habit (CIBH) was the most common referring clinical feature (38.3%). Patients diagnosed with CRC were significantly older than those without malignancy (74.0 years vs 68.9 years, p = 0.0007). Male patients were more likely to be diagnosed with CRC than females (6.5% vs 2.5%, Chi-squared 16.93, p = 100 microg Hb/g faeces group (55/181, 30.4%)., CONCLUSION: In a multivariate model, FIT outperforms age, sex and all symptoms prompting referral. FIT has greater stratification value than any referral symptoms. FIT does have value in patients with iron deficiency anaemia. Copyright © 2021. Springer Nature Switzerland AG.
    • Faecal immunochemical testing reduces demand and improves yield of Leicester's 2-week pathway for change in bowel habit

      Chapman, Caroline J
      Aim: We look at the effect of introducing the faecal immunochemical test (FIT) in the straight-to-test 2-week pathway for change in bowel habit (CIBH).; Method: The FIT in primary care triages 2-week wait (2WW) colorectal referrals for patients aged 60 years and above for straight-to-test CT colonography (CTC). We compare the impact of the FIT on numbers of 2WW CTCs, in the year before and after FIT, in both colorectal cancer (CRC) detection and cost-effectiveness at both 4 μg Hb/g faeces and 10 μg Hb/g faeces.; Results: At a threshold of 4 μg Hb/g faeces, the positive predictive value of the FIT for diagnosis of CRC is 5.0% with a negative predictive value of 99.8% and a polyp detection rate of 25.5%. The introduction of the FIT resulted in a reduction in the number of CTCs performed through the CIBH pathway from a mean of 143.9 per month prior to the FIT to 66.8 CTCs per month once the FIT was well established. Given a FIT threshold of 10 μg Hb/g the number of CTCs would be predicted to fall by 70.4% to 42.6 CTCs per month resulting in higher CRC and polyp detection rate, and an estimated annual cost saving of £238 258 in our institution.; Conclusion: The FIT use in primary care improves the yield of 2WW referrals for CIBH alone and reduces the burden and cost of investigations to exclude CRC. Improvements may be possible by increasing the cut-off employed, without adversely affecting the risk of missing a cancer.
    • Including a general practice endorsement letter with the testing kit in the Bowel Cancer Screening Programme: Results of a cluster randomised trial

      Chapman, Caroline J (Sage, 2021)
      OBJECTIVES: To evaluate the effect of general practitioner endorsement accompanying the screening kit rather than with the invitation letter on participation in the NHS Bowel Cancer Screening Programme and on the socioeconomic gradient in participation in the Programme., METHODS: The NHS Bowel Cancer Screening Programme in England is delivered via five regional hubs. In early 2016, we carried out a cluster-randomised trial, with hub-day of invitation as the randomisation unit. We randomised 150 hub-days of invitation to the intervention group, GP endorsement on the letter accompanying the guaiac faecal occult blood testing kit (75 hub-days, 197,366 individuals) or control, usual letter (75 hub-days, 197,476 individuals). The endpoint was participation, defined as return of a valid kit within 18 weeks of initial invitation. Because of the cluster randomisation, data were analysed by a hierarchical logistic regression, allowing a random effect for date of invitation. Socioeconomic status was represented by the index of multiple deprivation., RESULTS: Participation was 59.4% in the intervention group and 58.7% in the control group, a significant difference (p = 0.04). There was no heterogeneity of the effect of intervention by index of multiple deprivation. We found that there was some confounding between date and screening episode order (first or subsequent screen). This in turn may have induced confounding with age and slightly diluted the result., CONCLUSIONS: General practitioner endorsement induces a modest increase in participation in bowel cancer screening, but does not affect the socioeconomic gradient. When considering cluster randomisation as a research method, careful scrutiny of potential confounding is indicated in advance if possible and in analysis otherwise.
    • Service evaluation of faecal immunochemical testing and anaemia for risk stratification in the 2-week-wait pathway for colorectal cancer

      Chapman, Caroline J; Bunce, J; Ng, O; Logan, Richard F; Humes, David J; Banerjea, Ayan (John Wiley & Sons Ltd, 2019)
      Background: New national guidance on urgent referral for investigation of colorectal cancer included faecal occult blood testing in 2015. A service evaluation of faecal immunochemical testing (FIT) and anaemia as risk stratification tools in symptomatic patients suspected of having CRC was undertaken., Methods: Postal FIT was incorporated into the colorectal cancer 2-week wait (2WW) pathway for all patients without rectal bleeding in 2016. Patients were investigated in the 2WW pathway as normal, and outcomes of investigations were recorded prospectively. Anaemia was defined as a haemoglobin level below 120 g/l in women and 130 g/l in men., Results: FIT kits were sent to 1106 patients, with an 80.9 per cent return rate; 810 patients completed investigations and 40 colorectal cancers were diagnosed (4.9 per cent). FIT results were significantly higher in patients with anaemia (median (i.q.r.) 4.8 (0.8-34.1) versus 1.2 (0-6.4) mug Hb/g faeces in those without anaemia; P < 0.001). Some 60.4 per cent of patients (538 of 891) had a result lower than 4 mug haemoglobin (Hb) per g faeces (limit of detectability), and 69.7 per cent (621 of 891) had less than 10 mug Hb/g faeces. Some 60 per cent of patients with colorectal cancer had a FIT reading of 150 mug Hb/g faeces or more. For five colorectal cancers diagnosed in patients with a FIT value below 10 mug Hb/g faeces, there was either a palpable rectal mass or the patient was anaemic. A FIT result of more than 4 mug Hb/g faeces had 97.5 per cent sensitivity and 64.5 per cent specificity for a diagnosis of colorectal cancer. A FIT result above 4 mug Hb/g faeces and/or anaemia had a 100 per cent sensitivity and 45.3 per cent specificity for colorectal cancer diagnosis., Conclusion: FIT is most useful at the extremes of detectability; strongly positive readings predict high rates of colorectal cancer and other significant pathology, whereas very low readings in the absence of anaemia or a palpable rectal mass identify a group with very low risk. High return rates for FIT within this 2WW pathway indicate its acceptability.
    • Faecal immunochemical testing and blood tests for prioritization of urgent colorectal cancer referrals in symptomatic patients: a 2-year evaluation

      Bailey, James A; Weller, J; Chapman, Caroline J; Ford, Abby; Hardy, Katie; Morling, Joanne R; Simpson, J; Humes, David J; Banerjea, Ayan (Oxford University Press, 2021)
      Background: A novel pathway incorporating faecal immunochemical testing (FIT) for rapid colorectal cancer diagnosis (RCCD) was introduced in 2017. This paper reports on the service evaluation after 2 years of pathway implementation.; Methods: The RCCD protocol was based on FIT, blood results and symptoms to stratify adult patients in primary care. Two-week-wait (2WW) investigation was indicated for patients with rectal bleeding, rectal mass and faecal haemoglobin (fHb) level of 10 µg Hb/g faeces or above or 4 µg Hb/g faeces or more in the presence of anaemia, low ferritin or thrombocytosis, in all other symptom groups. Patients with 100 µg Hb/g faeces or above had expedited investigation . A retrospective audit of colorectal cancer detected between 2017 and 2019 was conducted, fHb thresholds were reviewed and critically assessed for cancer diagnoses.; Results: In 2 years, 14788 FIT tests were dispatched with 13361 (90.4 per cent) completed returns. Overall, fHb was less than 4 µg Hb/g faeces in 9208 results (68.9 per cent), 4-9.9 µg Hb/g in 1583 (11.8 per cent), 10-99.9 µg Hb/g in 1850 (13.8 per cent) and 100 µg Hb/g faeces or above in 720 (5.4 per cent). During follow-up (median 10.4 months), 227 colorectal cancers were diagnosed. The cancer detection rate was 0.1 per cent in patients with fHb below 4 µg Hb/g faeces, 0.6 per cent in those with fHb 4-9.9 µg Hb/g faeces, 3.3 per cent for fHb 10-99.9 µg Hb/g faeces and 20.7 per cent for fHb 100 µg Hb/g faeces or above. The detection rate in the cohort with 10-19.9 µg Hb/g faeces was 1.4 per cent, below the National Institute for Health and Care Excellence threshold for urgent referral. The colorectal cancer rate in patients with fHb below 20 µg Hb/g faeces was less than 0.3 per cent.; Conclusion: Use of FIT to "rule out" urgent referral from primary care misses a small number of cases. The threshold for referral may be adjusted with blood results to improve stratification .
    • GP access to FIT increases the proportion of colorectal cancers detected on urgent pathways in symptomatic patients in Nottingham

      Bailey, James A; Khawaja, A; Andrews, Helen; Weller, J; Chapman, Caroline J (Elsevier Ltd, 2021)
      OBJECTIVE: Service evaluation of GP access to Faecal Immunochemical Test (FIT) for colorectal cancer (CRC) detection in Nottinghamshire and use of FIT for "rule out", "rule in" and "first test selection"., DESIGN: Retrospective audit of FIT results, CRC outcomes and resource utilisation before and after introduction of FIT in Primary Care in November 2017. Data from the new pathway up to December 2018 was compared with previous experience., RESULTS: Between November 2017 and December 2018, 6747 GP FIT test requests yielded 5733 FIT results, of which 4082 (71.2%) were =150.0 mug Hb/g faeces. The proportion of "rule out" results =150.0 mug Hb/g faeces. The proportion of "rule out" results =150.0 mug Hb/g faeces was significantly lower (4.1% vs 8.1%, Chi squared 27.3,P < 0.0001). There was a 33% rise in urgent referrals across Nottingham overall during the evaluation period. 2 CRC diagnoses were made in 4082 patients who had FIT<4.0 mug Hb/g faeces. 58.4% of new CRC diagnoses associated with a positive FIT were early stage cancers (Stage I and II). The proportion of all CRC diagnoses that follow an urgent referral s rose after introduction of FIT., CONCLUSIONS: FIT allows GP's to select a more appropriate cohort for urgent investigation without a large number of missed diagnoses. FIT appears to promise a "stage migration" effect which may ultimately improve CRC outcomes.
    • Choice of faecal immunochemical test matters: comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer

      Chapman, Caroline J; Banerjea, Ayan; Humes, David J; Ford, Abby; Hardy, Katie; Djedovic, Natasha; Logan, Richard F; Morling, Joanne R (De Gruyter, 2021)
      OBJECTIVES: Currently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 mug Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed., METHODS: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 microg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons., RESULTS: A total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 microg Hb/g faeces for OC-S and 318.1 and 1.0 microg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 microg Hb/g faeces for both tests found an agreement of 88.1%, at 10 microg Hb/g faeces 91.7% and at 150 microg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001., CONCLUSIONS: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb. Copyright © 2020 Walter de Gruyter GmbH, Berlin/Boston.
    • Early clinical outcomes of a rapid colorectal cancer diagnosis pathway using faecal immunochemical testing in Nottingham

      Chapman, Caroline J; Thomas, C; Morling, Joanne R; Simpson, J; Humes, David J; Banerjea, Ayan; Clark, S. K (John Wiley & Sons Ltd, 2020)
      AIM: We introduced primary care access to faecal immunochemical testing (FIT) as a stratification tool for symptomatic patients considered to be at risk of colorectal cancer (CRC) prior to urgent referral. We aimed to evaluate clinical and pathway outcomes during the first 6 months of this novel approach., METHOD: FIT was recommended for all patients who consulted their general practitioner with lower gastrointestinal symptoms other than rectal bleeding and rectal mass. We undertook a retrospective audit of the results of FIT, related clinical outcomes and resource utilization on prospectively logged cases between November 2017 and May 2018., RESULTS: Of the 1862 FIT kits dispatched by post 91.4% were returned, with a median return time of 7 days (range 2-110 days); however, 1.3% of returned kits could not be analysed. FIT results >= 150.0 mug haemoglobin (Hb)/g faeces identified patients with a significantly higher risk of CRC (30.9% vs 1.4%, chi-square 167.1, P = 10.0 mug Hb/g faeces identified patients with significantly higher risk of significant noncancer bowel pathology (24.1% vs 4.9%, chi-square 73.6, P < 0.0001) and FIT results < 4.0 mug Hb/g faeces identified a group more likely to have non-CRC pathology (5.1% vs 2.4%, chi-square 3.9, P < 0.05). The CRC detection rate in 531 patients investigated after a FIT result of < 4.0 mug Hb/g faeces was 0.2%. In 899 investigated patients, a FIT result with a threshold of 4.0 mug Hb/g faeces had sensitivity 97.2% (85.5-99.9% CI), specificity 61.4% (58.1-64.7% CI), negative predictive value 99.8% (98.7-100.0% CI) and positive predictive value 9.5% (8.7-10.4% CI)., CONCLUSION: A symptomatic pathway incorporating FIT is feasible and appears more clinically effective than pathways based on age and symptoms alone. Copyright Colorectal Disease © 2019 The Association of Coloproctology of Great Britain and Ireland.
    • A method of correcting for the effect of temperature on low-contrast penetration measurement in urethane phantoms

      Peake, Edward; Warrington, Shaun; Morgan, Paul S; Gibson, Nicholas M (Elsevier Ltd, 2019)
      Urethane-based test objects are routinely used for ultrasound quality assurance because of their durability and robustness. The acoustic properties of these phantoms including speed of sound and attenuation, however, have a strong dependence on temperature. Reliable measurement of low-contrast penetration, which is widely used for ultrasound system quality assurance testing, with these phantoms is therefore problematic. To alleviate this, a correction method was proposed using speed of sound estimated by measuring filament target separation. The method was developed using a range of 17 transducer geometry and frequency combinations across 5 ultrasound systems and validated using a further 5 systems. This was found to reduce the uncertainty of low-contrast penetration measurement from an average 17.6 mm to 4.9 mm over the temperature range 8degreeC to 32degreeC. This represents a greater than threefold improvement in precision of low-contrast penetration measurement. Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
    • Aberrant visual pathway development in albinism: From retina to cortex

      Morgan, Paul S; Dineen, Robert A (John Wiley and Sons Ltd, 2019)
      Albinism refers to a group of genetic abnormalities in melanogenesis that are associated neuronal misrouting through the optic chiasm. We perform quantitative assessment of visual pathway structure and function in 23 persons with albinism (PWA) and 20 matched controls using optical coherence tomography (OCT), volumetric magnetic resonance imaging (MRI), diffusion tensor imaging and visual evoked potentials (VEP). PWA had a higher streamline decussation index (percentage of total tractography streamlines decussating at the chiasm) compared with controls (Z = -2.24, p = .025), and streamline decussation index correlated weakly with inter-hemispheric asymmetry measured using VEP (r = .484, p = .042). For PWA, a significant correlation was found between foveal development index and total number of streamlines (r = .662, p < .001). Significant positive correlations were found between peri-papillary retinal nerve fibre layer thickness and optic nerve (r = .642, p < .001) and tract (r = .663, p < .001) width. Occipital pole cortical thickness was 6.88% higher (Z = -4.10, p < .001) in PWA and was related to anterior visual pathway structures including foveal retinal pigment epithelium complex thickness (r = -.579, p = .005), optic disc (r = .478, p = .021) and rim areas (r = .597, p = .003). We were unable to demonstrate a significant relationship between OCT-derived foveal or optic nerve measures and MRI-derived chiasm size or streamline decussation index. Our novel tractographic demonstration of altered chiasmatic decussation in PWA corresponds to VEP measured cortical asymmetry and is consistent with chiasmatic misrouting in albinism. We also demonstrate a significant relationship between retinal pigment epithelium and visual cortex thickness indicating that retinal pigmentation defects in albinism lead to downstream structural reorganisation of the visual cortex. Copyright © 2018 Wiley Periodicals, Inc.
    • Accuracy of the doses computed by the Eclipse treatment planning system near and inside metal elements

      Panek, Rafal (Nature Publishing, 2022)
      Metal artefacts degrade clinical image quality which decreases the confidence of using computed tomography (CT) for the delineation of key structures for treatment planning and leads to dose errors in affected areas. In this work, we investigated accuracy of doses computed by the Eclipse treatment planning system near and inside metallic elements for two different computation algorithms. An impact of CT metal artefact reduction methods on the resulting calculated doses has also been assessed. A water phantom including Gafchromic film and metal inserts was irradiated (max dose 5 Gy) using a 6 MV photon beam. Three materials were tested: titanium, alloy 600, and tungsten. The phantom CT images were obtained with the pseudo-monoenergetic reconstruction (PMR) and the iterative metal artefact reduction (iMAR). Image sets were used for dose calculation using an Eclipse treatment planning station (TPS). Monte Carlo (MC) simulations were used to predict the true dose distribution in the phantom allowing for comparison with doses measured by film and calculated by TPS. Measured and simulated percentage depth doses (PDDs) were not statistically different (p > 0.618). Regional differences were observed at edges of metallic objects (max 8% difference). However, PDDs simulated with and without film were statistically different (p 0.078). PDDs obtained using other algorithms significantly differ from the MC values (p < 0.011). The Acuros XB algorithm with a dose-to-medium approach provides reliable dose calculation in all metal regions when using the Varian system. The inability of the AAA algorithm to model backscatter dose significantly limits its clinical application in the presence of metal. No significant impact on the dose calculation was found for a range of metal artefact reduction strategies. Copyright © 2022. The Author(s).
    • Activation induced changes in GABA: Functional MRS at 7T with MEGA-sLASER

      Auer, Dorothee P; Morgan, Paul S (Elsevier Ltd, 2017)
      Functional magnetic resonance spectroscopy (fMRS) has been used to assess the dynamic metabolic responses of the brain to a physiological stimulus non-invasively. However, only limited information on the dynamic functional response of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, is available. We aimed to measure the activation-induced changes in GABA unambiguously using a spectral editing method, instead of the conventional direct detection techniques used in previous fMRS studies. The Mescher-Garwood-semi-localised by adiabatic selective refocusing (MEGA-sLASER) sequence was developed at 7T to obtain the time course of GABA concentration without macromolecular contamination. A significant decrease (-12+/-5%) in the GABA to total creatine ratio (GABA/tCr) was observed in the motor cortex during a period of 10min of hand-clenching, compared to an initial baseline level (GABA/tCr =0.11+/-0.02) at rest. An increase in the Glx (glutamate and glutamine) to tCr ratio was also found, which is in agreement with previous findings. In contrast, no significant changes in NAA/tCr and tCr were detected. With consistent and highly efficient editing performance for GABA detection and the advantage of visually identifying GABA resonances in the spectra, MEGA-sLASER is demonstrated to be an effective method for studying of dynamic changes in GABA at 7T. Copyright © 2017 Elsevier Inc. All rights reserved.
    • An international survey of MRI qualification and certification frameworks with an emphasis on identifying elements of good practice

      Morgan, Paul S (Elsevier Ltd, 2017)
      The purpose of the study was to survey MRI qualification and certification frameworks in the major English-speaking countries (Australia, New Zealand, US, Canada, UK, Ireland) with the aim of identifying elements of good practice. The intention is to incorporate these elements in a national framework that could be used in supporting an MRI specialist register. The study was conducted using document analysis of MRI qualification and certification documents from these states with data triangulated through a web-based questionnaire amongst an expert group of MRI radiographers (n = 59) from the same states. Based on the results of the study, recommendations have been put forward for those countries that are in the process of developing such frameworks. The main recommendations include that a professional or regulatory body externally accredits MRI programmes and that learning outcomes be based on an MRI competence profile that addresses current and forecasted needs of the particular country. The MRI competence profile should encompass a novice-to expert continuum and be referenced directly to a national qualification framework. Ideally each level of expertise should be assessed and evidenced by a portfolio of CPD activities, including clinical and management case studies appropriate to that level. Copyright © 2016 The College of Radiographers. All rights reserved.
    • Analysis and results from a UK national dose audit of paediatric CT examinations

      Dunn, Matthew (2022)
      OBJECTIVE: To present the results following a UK national patient dose audit of paediatric CT examinations, to propose updated UK national diagnostic reference levels (DRLs) and to analyse current practice to see if any recommendations can be made to assist with optimisation., METHODS: A UK national dose audit was undertaken in 2019 focussing on paediatric CT examinations of the head, chest, abdomen/pelvis and cervical spine using the methods proposed by the International Commission on Radiological Protection. The audit pro-forma contained mandatory fields, of which the post-examination dosimetry (volume CT dose index and dose-length product) and the patient weight (for body examinations) were the most important., RESULTS: Analysis of the data submitted indicates that it is appropriate to propose national DRLs for CT head examinations in the 0-<1, 1-<5, 5-<10 and 10-<15 year age ranges. This extends the number of age categories of national DRLs from those at present and revises the existing values downwards. For CT chest examinations, it is appropriate to propose national DRLs for the first time in the UK for the 5-<15, 15-<30, 30-<50 and 50-<80 kg weight ranges. There were insufficient data received to propose national DRLs for abdomen/pelvis or cervical spine examinations. Recommendations towards optimisation focus on the use of tube current (mA) modulation, iterative reconstruction and the selection of examination tube voltage (kVp)., CONCLUSION: Updated UK national DRLs are proposed for paediatric CT examinations of the head and chest., ADVANCES IN KNOWLEDGE: A national patient dose audit of paediatric CT examinations has led to the proposal of updated national DRLs.
    • Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques

      Coffey, Frank; Morgan, Paul S (Nature Publishing, 2021)
      This study concerns glulisine, a rapid-acting insulin analogue that plays a fundamental role in diabetes management. We have applied a combination of methods namely X-ray crystallography, and biophysical characterisation to provide a detailed insight into the structure and function of glulisine. X-ray data provided structural information to a resolution of 1.26 A. Crystals belonged to the H3 space group with hexagonal (centred trigonal) cell dimensions a = b = 82.44 and c = 33.65 A with two molecules in the asymmetric unit. A unique position of D21Glu, not present in other fast-acting analogues, pointing inwards rather than to the outside surface was observed. This reduces interactions with neighbouring molecules thereby increasing preference of the dimer form. Sedimentation velocity/equilibrium studies revealed a trinary system of dimers and hexamers/dihexamers in dynamic equilibrium. This new information may lead to better understanding of the pharmacokinetic and pharmacodynamic behaviour of glulisine which might aid in improving formulation regarding its fast-acting role and reducing side effects of this drug.
    • Application of pattern recognition techniques for classification of pediatric brain tumors by in vivo 3T 1 H-MR spectroscopy-A multi-center study

      Rodriguez, Gutierrez, D; Jaspan, Tim; Morgan, Paul S; Grundy, Richard G; Auer, Dorothee P (John Wiley and Sons Ltd, 2018)
      PURPOSE: 3T magnetic resonance scanners have boosted clinical application of 1 H-MR spectroscopy (MRS) by offering an improved signal-to-noise ratio and increased spectral resolution, thereby identifying more metabolites and extending the range of metabolic information. Spectroscopic data from clinical 1.5T MR scanners has been shown to discriminate between pediatric brain tumors by applying machine learning techniques to further aid diagnosis. The purpose of this multi-center study was to investigate the discriminative potential of metabolite profiles obtained from 3T scanners in classifying pediatric brain tumors., METHODS: A total of 41 pediatric patients with brain tumors (17 medulloblastomas, 20 pilocytic astrocytomas, and 4 ependymomas) were scanned across four different hospitals. Raw spectroscopy data were processed using TARQUIN. Borderline synthetic minority oversampling technique was used to correct for the data skewness. Different classifiers were trained using linear discriminative analysis, support vector machine, and random forest techniques., RESULTS: Support vector machine had the highest balanced accuracy for discriminating the three tumor types. The balanced accuracy achieved was higher than the balanced accuracy previously reported for similar multi-center dataset from 1.5T magnets with echo time 20 to 32 ms alone., CONCLUSION: This study showed that 3T MRS can detect key differences in metabolite profiles for the main types of childhood tumors. Magn Reson Med 79:2359-2366, 2018. © 2017 International Society for Magnetic Resonance in Medicine. Copyright © 2017 International Society for Magnetic Resonance in Medicine.
    • Alterations in the microstructure of white matter in children and adolescents with Tourette syndrome measured using tract-based spatial statistics and probabilistic tractography

      Morgan, Paul S (Elsevier Ltd, 2018)
      Tourette syndrome (TS) is a neurodevelopmental disorder characterised by repetitive and intermittent motor and vocal tics. TS is thought to reflect fronto-striatal dysfunction and the aetiology of the disorder has been linked to widespread alterations in the functional and structural integrity of the brain. The aim of this study was to assess white matter (WM) abnormalities in a large sample of young patients with TS in comparison to a sample of matched typically developing control individuals (CS) using diffusion MRI. The study included 35 patients with TS (3 females; mean age: 14.0 +/- 3.3) and 35 CS (3 females; mean age: 13.9 +/- 3.3). Diffusion MRI data was analysed using tract-based spatial statistics (TBSS) and probabilistic tractography. Patients with TS demonstrated both marked and widespread decreases in axial diffusivity (AD) together with altered WM connectivity. Moreover, we showed that tic severity and the frequency of premonitory urges (PU) were associated with increased connectivity between primary motor cortex (M1) and the caudate nuclei, and increased information transfer between M1 and the insula, respectively. This is to our knowledge the first study to employ both TBSS and probabilistic tractography in a sample of young patients with TS. Our results contribute to the limited existing literature demonstrating altered connectivity in TS and confirm previous results suggesting in particular, that altered insular function contributes to increased frequency of PU. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
    • An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial)

      Akram, Perways; Ravenscroft, Jane C; Rogers, Andy; UK Dermatology Clinical Trials Network's HI-Light Vitiligo, Trial Team (Blackwell, 2021)
      BACKGROUND: Economic evidence for vitiligo treatments is absent., OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo., METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged >= 5 years) with active vitiligo affecting = 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015., RESULTS: The mean +/- SD cost per participant was 775 +/- 83.7 for NB-UVB, 813 +/- 111.4 for combination treatment and 600 +/- 96.2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was 211 (95% confidence interval 188-235), corresponding to a risk difference of 10.9% (number needed to treat = 9). The incremental cost was 1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was 173 (95% confidence interval 151-196), with a risk difference of 5.2% (number needed to treat = 19). The incremental cost was 3336 per successful treatment., CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay 1932 per additional treatment success. Copyright © 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
    • Automated segmentation of haematoma and perihaematomal oedema in MRI of acute spontaneous intracerebral haemorrhage

      Gallagher, Rebecca G; Swienton, David J; Morgan, Paul S; Dineen, Robert A (Elsevier Ltd, 2019)
      BACKGROUND: Spontaneous intracerebral haemorrhage (SICH) is a common condition with high morbidity and mortality. Segmentation of haematoma and perihaematoma oedema on medical images provides quantitative outcome measures for clinical trials and may provide important markers of prognosis in people with SICH., METHODS: We take advantage of improved contrast seen on magnetic resonance (MR) images of patients with acute and early subacute SICH and introduce an automated algorithm for haematoma and oedema segmentation from these images. To our knowledge, there is no previously proposed segmentation technique for SICH that utilises MR images directly. The method is based on shape and intensity analysis for haematoma segmentation and voxel-wise dynamic thresholding of hyper-intensities for oedema segmentation., RESULTS: Using Dice scores to measure segmentation overlaps between labellings yielded by the proposed algorithm and five different expert raters on 18 patients, we observe that our technique achieves overlap scores that are very similar to those obtained by pairwise expert rater comparison. A further comparison between the proposed method and a state-of-the-art Deep Learning segmentation on a separate set of 32 manually annotated subjects confirms the proposed method can achieve comparable results with very mild computational burden and in a completely training-free and unsupervised way., CONCLUSION: Our technique can be a computationally light and effective way to automatically delineate haematoma and oedema extent directly from MR images. Thus, with increasing use of MR images clinically after intracerebral haemorrhage this technique has the potential to inform clinical practice in the future. Copyright © 2019. Published by Elsevier Ltd.