Search

The article discusses strategies for Patient Blood Management (PBM) by managing perioperative anaemia and minimisation of blood loss. Topics include Great Britain's National Institute for Health and Care Excellence (NICE) guidelines for blood transfusion, detection and management of preoperative anaemia, and management of coagulopathy and haemorrhage.

Background: Multiple risk-prediction models are used in clinical practice to triage patients as being at low risk or high risk of ovarian cancer. In the ROCkeTS study, we aimed to identify the best diagnostic test for ovarian cancer in symptomatic patients, through head-to-head comparisons of risk-prediction models, in a real-world setting. Here, we report the results for the postmenopausal cohort., Methods: In this multicentre, prospective diagnostic accuracy study, we recruited newly presenting female patients aged 16-90 years with non-specific symptoms and raised CA125 or abnormal ultrasound results (or both) who had been referred via rapid access, elective clinics, or emergency presentations from 23 hospitals in the UK. Patients with normal CA125 and simple ovarian cysts of smaller than 5 cm in diameter, active non-ovarian malignancy, or previous ovarian malignancy, or those who were pregnant or declined a transvaginal scan, were ineligible. In this analysis, only postmenopausal participants were included. Participants completed a symptom questionnaire, gave a blood sample, and had transabdominal and transvaginal ultrasounds performed by International Ovarian Tumour Analysis consortium (IOTA)-certified sonographers. Index tests were Risk of Malignancy 1 (RMI1) at a threshold of 200, Risk of Malignancy Algorithm (ROMA) at multiple thresholds, IOTA Assessment of Different Neoplasias in the Adnexa (ADNEX) at thresholds of 3% and 10%, IOTA SRRisk model at thresholds of 3% and 10%, IOTA Simple Rules (malignant vs benign, or inconclusive), and CA125 at 35 IU/mL. In a post-hoc analysis, the Ovarian Adnexal and Reporting Data System (ORADS) at 10% was derived from IOTA ultrasound variables using established methods since ORADS was described after completion of recruitment. Index tests were conducted by study staff masked to the results of the reference standard. The comparator was RMI1 at the 250 threshold (the current UK National Health Service standard of care). The reference standard was surgical or biopsy tissue histology or cytology within 3 months, or a self-reported diagnosis of ovarian cancer at 12 month follow-up. The primary outcome was diagnostic accuracy at predicting primary invasive ovarian cancer versus benign or normal histology, assessed by analysing the sensitivity, specificity, C-index, area under receiver operating characteristic curve, positive and negative predictive values, and calibration plots in participants with conclusive reference standard results and available index test data. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN17160843)., Findings: Between July 13, 2015, and Nov 30, 2018, 1242 postmenopausal patients were recruited, of whom 215 (17%) had primary ovarian cancer. 166 participants had missing, inconclusive, or other reference standard results; therefore, data from a maximum of 1076 participants were used to assess the index tests for the primary outcome. Compared with RMI1 at 250 (sensitivity 82·9% [95% CI 76·7 to 88·0], specificity 87·4% [84·9 to 89·6]), IOTA ADNEX at 10% was more sensitive (difference of -13·9% [-20·2 to -7·6], p<0·0001) but less specific (difference of 28·5% [24·7 to 32·3], p<0·0001). ROMA at 29·9 had similar sensitivity (difference of -3·6% [-9·1 to 1·9], p=0·24) but lower specificity (difference of 5·2% [2·5 to 8·0], p=0·0001). RMI1 at 200 had similar sensitivity (difference of -2·1% [-4·7 to 0·5], p=0·13) but lower specificity (difference of 3·0% [1·7 to 4·3], p<0·0001). IOTA SRRisk model at 10% had similar sensitivity (difference of -4·3% [-11·0 to -2·3], p=0·23) but lower specificity (difference of 16·2% [12·6 to 19·8], p<0·0001). IOTA Simple Rules had similar sensitivity (difference of -1·6% [-9·3 to 6·2], p=0·82) and specificity (difference of -2·2% [-5·1 to 0·6], p=0·14). CA125 at 35 IU/mL had similar sensitivity (difference of -2·1% [-6·6 to 2·3], p=0·42) but higher specificity (difference of 6·7% [4·3 to 9·1], p<0·0001). In a post-hoc analysis, when compared with RMI1 at 250, ORADS achieved similar sensitivity (difference of -2·1%, 95% CI -8·6 to 4·3, p=0·60) and lower specificity (difference of 10·2%, 95% CI 6·8 to 13·6, p<0·0001)., Interpretation: In view of its higher sensitivity than RMI1 at 250, despite some loss in specificity, we recommend that IOTA ADNEX at 10% should be considered as the new standard-of-care diagnostic in ovarian cancer for postmenopausal patients., Funding: UK National Institute of Heath Research., Competing Interests: Declaration of interests SS reports a research grant from AoA Diagnostics for work with samples collected in this study but not reported within this manuscript. SS reports honoraria from AstraZeneca, Merck, and GSK and consultancy from GSK and Immunogen, all unrelated to this work. TB reports grants, personal fees, and travel support from Samsung Medison; travel support from Roche Diagnostics; and personal fees from GE Healthcare, all outside the submitted work. BVC and DT report consultancy work done by KU Leuven to help the implementation and testing of the IOTA ADNEX model in ultrasound machines by Samsung Medison and GE Healthcare, outside the submitted work. UM declares stock ownership awarded by University College London until October, 2021, in Abcodia. UM and AG-M report research collaboration contracts with QIMR Berghofer Medical Research Institute, iLOF (intelligent Lab on Fiber), RNA Guardian, Micronoma, Mercy Bioanalytics, and Synteny Biotechnology. SK reports an honorary role as an Ovacome charity trustee. DT, TB, and BVC are IOTA steering group members and developed the IOTA models. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aim: To investigate the level of statistical support available to UK radiology trainees, and to gather opinions regarding how support may affect their current and future research aspirations., Materials and Methods: An online survey was developed, piloted, and distributed to radiology trainees via the UK Radiology Academic Network for Trainees and training programme directors. Research experience, research aspirations, available and desired statistical support, and attitudes to statistics were surveyed and responses were collated., Results: Seventy-nine responses were received, only two (3%) of whom had allocated time for research. Only three (4%) respondents were content with their statistical support whereas 25 (32%) reported insufficient statistical support; 13 (52%) of these believed this impacted "considerably" on research aspirations. Sixty-six (84%) respondents desired dedicated statistical support, 40 (61%) of whom stated the amount required would likely be "moderate" and 26 (39%) "significant". Respondents believed support would be most helpful to analyse data already collected (41 responses, 54%) rather than research planning (25, 33%). Most respondents (60, 76%) had used self-help methods to learn research statistics but only 21 (35%) found this useful., Conclusion: Training schemes must improve the provision, access to, and awareness of statistical support so that any research efforts are performed to a high standard. Trainees should not be expected to participate in research without sufficient time, mentorship, and statistical support., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Magnetic resonance enterography and enteric ultrasonography are used to image Crohn's disease patients. Their diagnostic accuracy for presence, extent and activity of enteric Crohn's disease was compared., Objective: To compare diagnostic accuracy, observer variability, acceptability, diagnostic impact and cost-effectiveness of magnetic resonance enterography and ultrasonography in newly diagnosed or relapsing Crohn's disease., Design: Prospective multicentre cohort study., Setting: Eight NHS hospitals., Participants: Consecutive participants aged ≥ 16 years, newly diagnosed with Crohn's disease or with established Crohn's disease and suspected relapse., Interventions: Magnetic resonance enterography and ultrasonography., Main Outcome Measures: The primary outcome was per-participant sensitivity difference between magnetic resonance enterography and ultrasonography for small bowel Crohn's disease extent. Secondary outcomes included sensitivity and specificity for small bowel Crohn's disease and colonic Crohn's disease extent, and sensitivity and specificity for small bowel Crohn's disease and colonic Crohn's disease presence; identification of active disease; interobserver variation; participant acceptability; diagnostic impact; and cost-effectiveness., Results: Out of the 518 participants assessed, 335 entered the trial, with 51 excluded, giving a final cohort of 284 (133 and 151 in new diagnosis and suspected relapse cohorts, respectively). Across the whole cohort, for small bowel Crohn's disease extent, magnetic resonance enterography sensitivity [80%, 95% confidence interval (CI) 72% to 86%] was significantly greater than ultrasonography sensitivity (70%, 95% CI 62% to 78%), with a 10% difference (95% CI 1% to 18%; p  = 0.027). For small bowel Crohn's disease extent, magnetic resonance enterography specificity (95%, 95% CI 85% to 98%) was significantly greater than ultrasonography specificity (81%, 95% CI 64% to 91%), with a 14% difference (95% CI 1% to 27%). For small bowel Crohn's disease presence, magnetic resonance enterography sensitivity (97%, 95% CI 91% to 99%) was significantly greater than ultrasonography sensitivity (92%, 95% CI 84% to 96%), with a 5% difference (95% CI 1% to 9%). For small bowel Crohn's disease presence, magnetic resonance enterography specificity was 96% (95% CI 86% to 99%) and ultrasonography specificity was 84% (95% CI 65% to 94%), with a 12% difference (95% CI 0% to 25%). Test sensitivities for small bowel Crohn's disease presence and extent were similar in the two cohorts. For colonic Crohn's disease presence in newly diagnosed participants, ultrasonography sensitivity (67%, 95% CI 49% to 81%) was significantly greater than magnetic resonance enterography sensitivity (47%, 95% CI 31% to 64%), with a 20% difference (95% CI 1% to 39%). For active small bowel Crohn's disease, magnetic resonance enterography sensitivity (96%, 95% CI 92% to 99%) was significantly greater than ultrasonography sensitivity (90%, 95% CI 82% to 95%), with a 6% difference (95% CI 2% to 11%). There was some disagreement between readers for both tests. A total of 88% of participants rated magnetic resonance enterography as very or fairly acceptable, which is significantly lower than the percentage (99%) of participants who did so for ultrasonography. Therapeutic decisions based on magnetic resonance enterography alone and ultrasonography alone agreed with the final decision in 122 out of 158 (77%) cases and 124 out of 158 (78%) cases, respectively. There were no differences in costs or quality-adjusted life-years between tests., Limitations: Magnetic resonance enterography and ultrasonography scans were interpreted by practitioners blinded to clinical data (but not participant cohort), which does not reflect use in clinical practice., Conclusions: Magnetic resonance enterography has higher accuracy for detecting the presence, extent and activity of small bowel Crohn's disease than ultrasonography does. Both tests have variable interobserver agreement and are broadly acceptable to participants, although ultrasonography produces less participant burden. Diagnostic impact and cost-effectiveness are similar. Recommendations for future work include investigation of the comparative utility of magnetic resonance enterography and ultrasonography for treatment response assessment and investigation of non-specific abdominal symptoms to confirm or refute Crohn's disease., Trial Registration: Current Controlled Trials ISRCTN03982913., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 42. See the NIHR Journals Library website for further project information., Competing Interests: Stuart A Taylor reports personal fees from Robarts Clinical Trials Inc. (London, ON, Canada) outside the submitted work. Simon Travis reports receiving fees for consultancy work and/or speaking engagements from the following: AbbVie Inc. (Chicago, IL, USA), Centocor Inc. (Horsham, PA, USA), Schering-Plough (Kenilworth, NJ, USA), Bristol-Myers Squibb (New York, NY, USA), Chemocentryx Inc. (Mountain View, CA, USA), Cosmo Pharmaceuticals (Dublin, Ireland), Elan Pharma Inc. (Dublin, Ireland), Genentech Inc. (San Francisco, CA, USA), Giuliani SpA (Milan, Italy), Merck & Co. Inc. (Kenilworth, NJ, USA), Takeda UK Ltd (Woodburn Green, Buckinghamshire, UK), Otsuka Pharmaceuticals (Tokyo, Japan), PDL BioPharma (Nevada, NV, USA), Pfizer Inc. (San Francisco, CA, USA), Shire Pharmaceuticals UK (St Helier, Jersey), Glenmark Pharmaceuticals (Maharashtra, India), Synthon Biopharmaceuticals (Nijmegen, the Netherlands), NPS Pharmaceuticals (Bedminster, NJ, USA), Eli Lilly and Company (Indiana, IN, USA), Warner Chilcott Ltd, Proximagen Group Ltd (London, UK), VHsquared Ltd (Cambridge, UK), Topivert Pharma Ltd (London, UK), Ferring Pharmaceuticals (Saint-Prex, Switzerland), Celgene Corporation (Summit, NJ, USA), GlaxoSmithKline plc (Brentford, UK), Amgen Inc. (Thousand Oaks, CA, USA), Biogen Inc. (Cambridge, MA, USA), Enterome SA (Paris, France), Immunocore Ltd (Oxford, UK), Immunometabolism/Third Rock Ventures (Boston, MA, USA), Bioclinica Inc. (Newtown, PA, USA), Boehringer Ingelheim GmBH (Ingelheim am Rhein, Germany), Gilead Sciences Inc. (Foster City, CA, USA), Grunenthal Ltd (Aachen, Germany), Janssen Pharmaceutica (Beerse, Belgium), Novartis AG (Basel, Switzerland), Receptos Inc. (San Diego, CA, USA), Pharm-Olam International UK Ltd (Bracknell, UK), Sigmoid Pharma (Dublin, Ireland), Theravance Biopharma Inc. (Dublin, Ireland), Given Imaging Ltd (Yokneam Illit, Israel), UCB Pharma SA (Brussels, Belgium), Tillotts Pharma AG (Rheinfelden, Switzerland), Sanofi Aventis SA (Paris, France), Vifor Pharma (St Gallen, Switzerland), Abbott Laboratories Ltd (Chicago, IL, USA) and Procter and Gamble Ltd (Cincinnati, OH, USA). Simon Travis reports directorships of charities IBD2020 (Barnet, UK; UK 09762150), Cure Crohn’s Colitis (Sydney, Australia; ABN 85 154 588 717) and the Truelove Foundation (London, UK; UK 11056711). Simon Travis also reports receiving fees from the following for expert testimony work and/or royalties: Santarus Inc. (San Diego, CA, USA), Cosmo Technologies Ltd (Dublin, Ireland), Tillotts Pharma AG, Wiley-Blackwell Inc. (Hoboken, NJ, USA), Elsevier Ltd (Amsterdam, the Netherlands) and Oxford University Press (Oxford, UK). Simon Travis has received research grants from the following: AbbVie Inc., the International Organization for the Study of Inflammatory Bowel Disease, Eli Lilly and Company, UCB Inc. (Brussels, Belgium), Vifor Pharma, Norman Collisson Foundation (Bicester, UK), Ferring Pharmaceuticals, Schering-Plough, Merck Sharpe & Dohme Corp. (Kenilworth, NJ, USA), Procter and Gamble Ltd, Warner Chilcott Ltd, Abbott Laboratories Ltd, PDL BioPharma Inc. (Incline Village, NV, USA), Takeda UK Ltd and the International Consortium for Health Care Outcomes Measurement. Ailsa Hart reports personal fees from AbbVie Inc., Atlantic Healthcare Ltd (Saffron Walden, UK), Bristol-Myers Squibb, Celltrion Inc. (Incheon, South Korea), Dr Falk Pharma UK Ltd (Bourne End, UK), Ferring Pharmaceuticals, Janssen Pharmaceuticals, Merck Sharpe & Dohme Corp., Napp Pharmaceuticals Ltd (Cambridge, UK), Pfizer Inc., Pharmacosmos A/S (Holbæk, Denmark), Shire Pharmaceuticals UK and Takeda UK Ltd, and non-financial support from Genentech Inc. Alastair Windsor reports personal fees from Takeda, grants from Allergan Inc. (Dublin, Ireland), personal fees from Allergan, personal fees from Cook Medical Inc. (Bloomington, IN, USA) and grants and personal fees from Bard Ltd (Crawley, UK) outside the submitted work. Andrew Plumb reports grants from the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme outside the submitted work, grants from the NIHR Fellowships programme during the conduct of the study and honoraria for educational lectures delivered at events arranged by Acelity Inc. (Crawley, UK), Actavis Pharma Inc. (Parsippany-Troy Hills, NJ, USA), Dr Falk Pharma UK Ltd, Janssen-Cilag Ltd (High Wycombe, UK) and Takeda UK Ltd on the subject of inflammatory bowel disease. Ilan Jacobs reports share ownership in General Electric Company (Boston, MA, USA), which manufacturers and sells magnetic resonance imaging equipment. Charles D Murray reports personal fees from AbbVie Inc., Merck Sharpe & Dohme Corp. and Janssen Pharmaceutica outside the submitted work. Antony Higginson reports personal fees from Toshiba Corporation (Tokyo, Japan) outside the submitted work. Steve Halligan reports non-financial support from iCAD Inc. (Nashua, NH, USA) outside the submitted work, and sat on the HTA commissioning board (2008–14). Stephen Morris reports Health Services and Delivery Research (HSDR) Board membership (2014–18), HSDR Evidence Synthesis Sub Board membership (2016), HTA Commissioning Board membership (2009–13) and Public Health Research Board membership (2011–17).

Introduction: Influenza and influenza-like illness (ILI) create considerable burden on healthcare resources each winter. Children with pre-existing conditions such as asthma, diabetes mellitus and cerebral palsy are among those at greatest risk of clinical deterioration from influenza/ILI. The Antibiotics for at Risk CHildren with InfluEnza (ARCHIE) trial aims to determine whether early oral treatment with the antibiotic co-amoxiclav reduces the likelihood of reconsultation due to clinical deterioration in these 'at risk' children., Methods and Analysis: The ARCHIE trial is a double-blind, parallel, randomised, placebo-controlled trial. 'At risk' children aged 6 months to 12 years inclusive who present within the first 5 days of an ILI episode will be randomised to receive a 5-day course of oral co-amoxiclav 400/57 twice daily or placebo. Randomisation will use a non-deterministic minimisation algorithm to balance age and seasonal influenza vaccination status.To detect respiratory virus infections, a nasal swab will be obtained from each participant before commencing study medication. To identify carriage of potential bacterial respiratory pathogens, we will also obtain a throat swab where possible.The primary outcome is reconsultation in any healthcare setting due to clinical deterioration within 28 days of randomisation. We will analyse this outcome using log-binomial regression model adjusted for region, age and seasonal influenza vaccination status.Secondary outcomes include duration of fever, duration of symptoms and adverse events. Continuous outcomes will be compared using regression analysis (or equivalent non-parametric method for non-normal data) adjusting for minimisation variables. Binary outcomes will be compared using χ 2 /Fisher's exact test and log-binomial regression., Ethics: The ARCHIE trial has been reviewed and approved by the North West-Liverpool East Research Ethics Committee, Health Research Authority and Medicines and Healthcare Products Regulatory Agency. Our findings will be published in peer-reviewed journals and disseminated via our study website (www.archiestudy.com) and links with relevant charities., Trial Registration Numbers: ISRCTN 70714783; Pre-results. EudraCT 2013-002822-21; Pre-results., Competing Interests: Competing interests: KW is a National Institute for Health Research (NIHR) Postdoctoral Fellow. AF is a NIHR Senior Investigator and is supported by the Oxford NIHR Biomedical Research Centre. AH is Deputy Chairman of the Joint Committee on Vaccination and Immunisation, which advises the UK government on vaccine policy. MGS is an NIHR Investigator, is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections and is a member of the New and Emerging Respiratory Viral Threats Advisory Group, whose remit includes advice to the UK government on antibiotic and antiviral stockpile policy., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Ovarian cancer (OC) is associated with non-specific symptoms such as bloating, making accurate diagnosis challenging: only 1 in 3 women with OC presents through primary care referral. National Institute for Health and Care Excellence guidelines recommends sequential testing with CA125 and routine ultrasound in primary care. However, these diagnostic tests have limited sensitivity or specificity. Improving accurate triage in women with vague symptoms is likely to improve mortality by streamlining referral and care pathways. The Refining Ovarian Cancer Test Accuracy Scores (ROCkeTS; HTA 13/13/01) project will derive and validate new tests/risk prediction models that estimate the probability of having OC in women with symptoms. This protocol refers to the prospective study only (phase III)., Methods and Analysis: ROCkeTS comprises four parallel phases. The full ROCkeTS protocol can be found at http://www.birmingham.ac.uk/ROCKETS. Phase III is a prospective test accuracy study. The study will recruit 2450 patients from 15 UK sites. Recruited patients complete symptom and anxiety questionnaires, donate a serum sample and undergo ultrasound scored as per International Ovarian Tumour Analysis (IOTA) criteria. Recruitment is at rapid access clinics, emergency departments and elective clinics. Models to be evaluated include those based on ultrasound derived by the IOTA group and novel models derived from analysis of existing data sets. Estimates of sensitivity, specificity, c-statistic (area under receiver operating curve), positive predictive value and negative predictive value of diagnostic tests are evaluated and a calibration plot for models will be presented. ROCkeTS has received ethical approval from the NHS West Midlands REC (14/WM/1241) and is registered on the controlled trials website (ISRCTN17160843) and the National Institute of Health Research Cancer and Reproductive Health portfolios., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To evaluate the performance of the QFractureScores for predicting the 10 year risk of osteoporotic and hip fractures in an independent UK cohort of patients from general practice records., Design: Prospective cohort study., Setting: 364 UK general practices contributing to The Health Improvement Network (THIN) database., Participants: 2.2 million adults registered with a general practice between 27 June 1994 and 30 June 2008, aged 30-85 (13 million person years), with 25,208 osteoporotic fractures and 12,188 hip fractures., Main Outcome Measures: First (incident) diagnosis of osteoporotic fracture (vertebra, distal radius, or hip) and incident hip fracture recorded in general practice records., Results: Results from this independent and external validation of QFractureScores indicated good performance data for both osteoporotic and hip fracture end points. Discrimination and calibration statistics were comparable to those reported in the internal validation of QFractureScores. The hip fracture score had better performance data for both women and men. It explained 63% of the variation in women and 60% of the variation in men, with areas under the receiver operating characteristic curve of 0.89 and 0.86, respectively. The risk score for osteoporotic fracture explained 49% of the variation in women and 38% of the variation in men, with corresponding areas under the receiver operating characteristic curve of 0.82 and 0.74. QFractureScores were well calibrated, with predicted risks closely matching those across all 10ths of risk and for all age groups., Conclusion: QFractureScores are useful tools for predicting the 10 year risk of osteoporotic and hip fractures in patients in the United Kingdom.