NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer.

BACKGROUND: Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients' quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. METHODS: NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. DISCUSSION: NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. TRIAL REGISTRATION: NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

Colorectal Cancer: Performance and Evaluation for CT Colonography Screening- A Multicenter Cluster-randomized Controlled Trial.

Background Most radiologists reporting CT colonography (CTC) do not undergo compulsory performance accreditation, potentially lowering diagnostic sensitivity. Purpose To determine whether 1-day individualized training in CTC reporting improves diagnostic sensitivity of experienced radiologists for 6-mm or larger lesions, the durability of any improvement, and any associated factors. Materials and Methods This prospective, multicenter cluster-randomized controlled trial was performed in National Health Service hospitals in England and Wales between April 2017 and January 2020. CTC services were cluster randomized into intervention (1-day training plus feedback) or control (no training or feedback) arms. Radiologists in the intervention arm attended a 1-day workshop focusing on CTC reporting pitfalls with individualized feedback. Radiologists in the control group received no training. Sensitivity for 6-mm or larger lesions was tested at baseline and 1, 6, and 12 months thereafter via interpretation of 10 CTC scans at each time point. The primary outcome was the mean difference in per-lesion sensitivity between arms at 1 month, analyzed using multilevel regression after adjustment for baseline sensitivity. Secondary outcomes included per-lesion sensitivity at 6- and 12-month follow-up, sensitivity for flat neoplasia, and effect of prior CTC experience. Results A total of 69 hospitals were randomly assigned to the intervention (31 clusters, 80 radiologists) or control (38 clusters, 59 radiologists) arm. Radiologists were experienced (median, 500-999 CTC scans interpreted) and reported CTC scans routinely (median, 151-200 scans per year). One-month sensitivity improved after intervention (66.4% [659 of 992]) compared with sensitivity in the control group (42.4% [278 of 655]; difference = 20.8%; 95% CI: 14.6, 27.0; P < .001). Improvements were maintained at 6 (66.4% [572 of 861] vs 50.5% [283 of 560]; difference = 13.0%; 95% CI: 7.4, 18.5; P < .001) and 12 (63.7% [310 of 487] vs 44.4% [187 of 421]; difference = 16.7%; 95% CI: 10.3, 23.1; P < .001) months. This beneficial effect applied to flat lesions (difference = 22.7%; 95% CI: 15.5, 29.9; P < .001) and was independent of career experience (≥1500 CTC scans: odds ratio = 1.09; 95% CI: 0.88, 1.36; P = .22). Conclusion For radiologists evaluating CT colonography studies, a 1-day training intervention yielded sustained improvement in detection of clinically relevant colorectal neoplasia, independent of previous career experience. Clinical trial registration no. NCT02892721 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Pickhardt in this issue. An earlier incorrect version appeared online and in print. This article was corrected on February 28, 2022.

Effect of post-operative goal-directed fluid therapy (GDFT) on organ function after orthotopic liver transplantation: Secondary outcome analysis of the COLT randomised control trial.

BACKGROUND: Goal-directed fluid therapy (GDFT) has been shown to reduce the complications following a variety of major surgical procedures, possibly mediated by improved organ perfusion and function. We have shown that it is feasible to randomise patients to GDFT or standard fluid management following liver transplant in the cardiac-output optimisation following liver transplantation (COLT) trial. The current study compares end organ function in patients from the COLT trial who received GDFT in comparison to those receiving standard care (SC) following liver transplant. METHODS: Adult patients with liver cirrhosis undergoing liver transplantation were randomised to GDFT or SC for the first 12 h following surgery as detailed in a published trial protocol. GDFT protocol was based on stroke volume (SV) optimisation using 250 ml crystalloid boluses. Total fluid administration and time to extubation were recorded. Hourly SV and cardiac output (CO) readings were recorded from the non-invasive cardiac output monitoring (NICOM) device in both groups. Pulmonary function was assessed by arterial blood gas (ABG) and ventilatory parameters. Lung injury was assessed using PaO2:FiO2 ratios and calculated pulmonary compliance. The KDIGO score was used for determining acute kidney injury. Renal and liver graft function were assessed during the post-operative period and at 3 months and 1-year. RESULTS: 60 patients were randomised to GDFT (n = 30) or SC (n = 30). All patients completed the 12 h intervention period. GDFT group received a significantly higher total volume of fluid during the 12 h trial intervention period (GDFT 5317 (2335) vs. SC 3807 (1345) ml, p = 0.003); in particular crystalloids (GDFT 3968 (2073) vs. SC 2510 (1027) ml, p = 0.002). There was no evidence of significant difference between the groups in SV or CO during the assessment periods. Time to extubation, PaO2: FIO2 ratios, pulmonary compliance, ventilatory or blood gas measurements were similar in both groups. There was a significant rise in serum creatinine from baseline (77 µmol/L) compared to first (87 µmol/L, p = 0.039) and second (107 µmol/L, p = 0.001) post-operative days. There was no difference between GDFT and SC in the highest KDIGO scores for the first 7 days post-LT. At 1-year follow-up, there was no difference in need for renal replacement therapy or graft function. CONCLUSIONS: In this randomised trial of fluid therapy post liver transplant, GDFT was associated with an increased volume of crystalloids administered but did not alter early post-operative pulmonary or renal function when compared with standard care.

Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease.

BACKGROUND: There is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead. AIMS: To assess the diagnostic accuracy of serological tests for coeliac disease in adults and children. METHODS: Seven electronic databases were searched between January 1990 and August 2020. Eligible diagnostic studies evaluated the accuracy of serological tests for coeliac disease against duodenal biopsy. Risk of bias assessment was performed using QUADAS-2. Bivariate random-effects meta-analyses were used to estimate serology sensitivity and specificity at the most commonly reported thresholds. RESULTS: 113 studies (n = 28,338) were included, all in secondary care populations. A subset of studies were included in meta-analyses due to variations in diagnostic thresholds. Summary sensitivity and specificity of immunoglobulin A (IgA) anti-tissue transglutaminase were 90.7% (95% confidence interval: 87.3%, 93.2%) and 87.4% (84.4%, 90.0%) in adults (5 studies) and 97.7% (91.0%, 99.4%) and 70.2% (39.3%, 89.6%) in children (6 studies); and of IgA endomysial antibodies were 88.0% (75.2%, 94.7%) and 99.6% (92.3%, 100%) in adults (5 studies) and 94.5% (88.9%, 97.3%) and 93.8% (85.2%, 97.5%) in children (5 studies). CONCLUSIONS: Anti-tissue transglutaminase sensitivity appears to be sufficient to rule out coeliac disease in children. The high specificity of endomysial antibody in adults supports its use to rule in coeliac disease. This evidence underpins the current development of clinical guidelines for a serological diagnosis of coeliac disease. Studies in primary care are needed to evaluate serological testing strategies in this setting.

The accuracy of diagnostic indicators for coeliac disease: A systematic review and meta-analysis.

BACKGROUND: The prevalence of coeliac disease (CD) is around 1%, but diagnosis is challenged by varied presentation and non-specific symptoms and signs. This study aimed to identify diagnostic indicators that may help identify patients at a higher risk of CD in whom further testing is warranted. METHODS: International guidance for systematic review methods were followed and the review was registered at PROSPERO (CRD42020170766). Six databases were searched until April 2021. Studies investigating diagnostic indicators, such as symptoms or risk conditions, in people with and without CD were eligible for inclusion. Risk of bias was assessed using the QUADAS-2 tool. Summary sensitivity, specificity, and positive predictive values were estimated for each diagnostic indicator by fitting bivariate random effects meta-analyses. FINDINGS: 191 studies reporting on 26 diagnostic indicators were included in the meta-analyses. We found large variation in diagnostic accuracy estimates between studies and most studies were at high risk of bias. We found strong evidence that people with dermatitis herpetiformis, migraine, family history of CD, HLA DQ2/8 risk genotype, anaemia, type 1 diabetes, osteoporosis, or chronic liver disease are more likely than the general population to have CD. Symptoms, psoriasis, epilepsy, inflammatory bowel disease, systemic lupus erythematosus, fractures, type 2 diabetes, and multiple sclerosis showed poor diagnostic ability. A sensitivity analysis revealed a 3-fold higher risk of CD in first-degree relatives of CD patients. CONCLUSIONS: Targeted testing of individuals with dermatitis herpetiformis, migraine, family history of CD, HLA DQ2/8 risk genotype, anaemia, type 1 diabetes, osteoporosis, or chronic liver disease could improve case-finding for CD, therefore expediting appropriate treatment and reducing adverse consequences. Migraine and chronic liver disease are not yet included as a risk factor in all CD guidelines, but it may be appropriate for these to be added. Future research should establish the diagnostic value of combining indicators.

Accuracy of potential diagnostic indicators for coeliac disease: a systematic review protocol.

INTRODUCTION: Coeliac disease (CD) is a systemic immune-mediated disorder triggered by gluten in genetically predisposed individuals. CD is diagnosed using a combination of serology tests and endoscopic biopsy of the small intestine. However, because of non-specific symptoms and heterogeneous clinical presentation, diagnosing CD is challenging. Early detection of CD through improved case-finding strategies can improve the response to a gluten-free diet, patients' quality of life and potentially reduce the risk of complications. However, there is a lack of consensus in which groups may benefit from active case-finding. METHODS AND ANALYSIS: We will perform a systematic review to determine the accuracy of diagnostic indicators (such as symptoms and risk factors) for CD in adults and children, and thus can help identify patients who should be offered CD testing. MEDLINE, Embase, Cochrane Library and Web of Science will be searched from 1997 until 2020. Screening will be performed in duplicate. Data extraction will be performed by one and checked by a second reviewer. Disagreements will be resolved through discussion or referral to a third reviewer. We will produce a narrative summary of identified prediction models. Studies, where 2×2 data can be extracted or reconstructed, will be treated as diagnostic accuracy studies, that is, the diagnostic indicators are the index tests and CD serology and/or biopsy is the reference standard. For each diagnostic indicator, we will perform a bivariate random-effects meta-analysis of the sensitivity and specificity. ETHICS AND DISSEMINATION: Results will be reported in peer-reviewed journals, academic and public presentations and social media. We will convene an implementation panel to advise on the optimum strategy for enhanced dissemination. We will discuss findings with Coeliac UK to help with dissemination to patients. Ethical approval is not applicable, as this is a systematic review and no research participants will be involved. PROSPERO REGISTRATION NUMBER: CRD42020170766.

How to avoid describing your radiological research study incorrectly.

This review identifies and examines terms used to describe a radiological research "study" or "trial". A taxonomy of clinical research descriptions is explained with reference to medical imaging examples. Because many descriptive terms have precise methodological implications, it is important that these terms are understood by readers and used correctly by researchers, so that the reader is not misled. KEY POINTS: • Multiple different terms are being used to describe radiological research "studies" and "trials", and many of these terms have precise methodological implications. • Radiological researchers sometimes use titles that describe their research incorrectly. This can mislead the reader as to what was actually done. • It is important that readers and researchers understand the correct taxonomy of clinical research and that researchers adopt the correct description for their work.

Observer agreement for small bowel ultrasound in Crohn's disease: results from the METRIC trial.

PURPOSE: To prospectively evaluate interobserver agreement for small bowel ultrasound (SBUS) in newly diagnosed and relapsing Crohn's disease. METHODS: A subset of patients recruited to a prospective trial comparing the diagnostic accuracy of MR enterography and SBUS underwent a second SBUS performed by one of a pool of six practitioners, who recorded the presence, activity and location of small bowel and colonic disease. Detailed segmental mural and extra-mural observations were also scored. Interobserver variability was expressed as percentage agreement with a construct reference standard, split by patient cohort, grouping disease as present or absent. Prevalence adjusted bias adjusted kappa (PABAK), and simple percentage agreement between practitioners, irrespective of the reference standard, were calculated. RESULTS: Thirty-eight patients (11 new diagnosis, 27 relapse) were recruited from two sites. Overall percentage agreement for small bowel disease presence against the consensus reference was 82% (52-95% (95%CI)), kappa coefficient (κ) 0.64, (substantial agreement) for new diagnosis and 81%, κ 0.63 (substantial agreement) for the relapsing cohort. Agreement for colonic disease presence was 64%, κ 0.27 (fair agreement) in new diagnosis and 78%,κ 0.56 (moderate agreement) in the relapsing cohort. Simple agreement between practitioners was 84% and 87% for small bowel and colonic disease presence respectively. Practitioners agreed on small bowel disease activity in 24/27 (89%) where both identified disease. Kappa agreement for detailed mural observations ranged from κ 0.00 to 1.00. CONCLUSION: There is substantial practitioner agreement for small bowel disease presence in newly diagnosed and relapsing CD patients, supporting wider dissemination of enteric US.

The choice and definition of summary measure for meta-analysis of clinical studies with binary outcomes: effect on clinical interpretation.

Many systematic reviews and meta-analyses concern the effect of a healthcare intervention on a binary outcome i.e. occurrence (or not) of a particular event. Usually, the overall effect, pooled across all studies included in the meta-analysis, is summarised using the odds ratio (OR) or the relative risk (RR). Under most circumstances, it is obvious how to identify what should be considered as the event of interest-for example, death or a clinically important side-effect. However, on occasion it may not be clear in which "direction" the event should be specified-such as attendance (vs non-attendance) at cancer screening. Usually, this choice is not critical to the overall conclusion of the meta-analysis, but occasionally it can lead to differences in how the included studies are pooled, ultimately affecting the overall meta-analytic result, particularly when using RRs rather than ORs. In this commentary, we will explain this phenomenon in more detail using examples from the literature, and explore how analysts and readers can avoid some potential pitfalls.

Serum HE4 and diagnosis of ovarian cancer in postmenopausal women with adnexal masses.

BACKGROUND: Transvaginal ultrasound and serum CA125 are routinely used for differential diagnosis of pelvic adnexal mass. Use of human epididymis 4 was approved in the United States in 2011. However, there is scarcity of studies evaluating the additional value of human epididymis 4. OBJECTIVE: The objective of the study was to evaluate the performance characteristics of transvaginal ultrasound, CA125, and human epididymis 4 for differential diagnosis of ovarian cancer in postmenopausal women with adnexal masses. STUDY DESIGN: This was a cohort study nested within the screen arms of the multicenter randomized controlled trial, United Kingdom Collaborative Trial of Ovarian Cancer Screening, based in England, Wales, and Northern Ireland. In United Kingdom Collaborative Trial of Ovarian Cancer Screening, 48,230 women randomized to transvaginal ultrasound screening and 50,078 to multimodal screening (serum CA125 interpreted by Risk of Ovarian Cancer Algorithm with second line transvaginal ultrasound) underwent the first (prevalence) screen. Women with adnexal lesions and/or persistently elevated risk were clinically assessed and underwent surgery or follow-up for a median of 10.9 years. Banked samples taken within 6 months of transvaginal ultrasound from all clinically assessed women were assayed for human epididymis 4 and CA125. Area under the curve and sensitivity for diagnosing ovarian cancer of multiple penalized logistic regression models incorporating logCA125, log human epididymis 4, age, and simple ultrasound features of the adnexal mass were compared. RESULTS: Of 1590 (158 multimodal, 1432 ultrasound) women with adnexal masses, 78 were diagnosed with ovarian cancer (48 invasive epithelial ovarian, 14 type I, 34 type II; 24 borderline epithelial; 6 nonepithelial) within 1 year of scan. The area under the curve (0.893 vs 0.896; P = .453) and sensitivity (74.4% vs 75.6% ;P = .564) at fixed specificity of 90% of the model incorporating age, ultrasound, and CA125 were similar to that also including human epididymis 4. Both models had high sensitivity for invasive epithelial ovarian (89.6%) and type II (>91%) cancers. CONCLUSION: Our population cohort study suggests that human epididymis 4 adds little value to concurrent use of CA125 and transvaginal ultrasound in the differential diagnosis of adnexal masses in postmenopausal women.

The cardiac output optimisation following liver transplant (COLT) trial: a feasibility randomised controlled trial.

BACKGROUND: Perioperative goal directed fluid therapy (GDFT) has been shown to reduce postoperative complications following major surgery; this intervention has not been formally evaluated in the setting of liver transplantation. METHODS: We conducted a prospective trial of GDFT following liver transplantation randomising patients with liver cirrhosis to either 12 h of GDFT using non-invasive cardiac output monitoring or standard care (SC). The primary outcome was feasibility. Secondary outcomes included survival, postoperative complications (Clavien-Dindo), quality of life (by EQ-5D-5L) and resource use. Trial specific follow up occurred at 90 and 180 days after surgery. RESULTS: The study was feasible. Of 224 eligible patients, 122 were approached, 114 consented to participate and 60 were enrolled into the trial. The mean (SD) volume of IV crystalloid administered to the GDFT group during the 12-h study period was 3968 (2073) ml for the GDFT group and 2510 (1026) ml for the SC group. As regards secondary outcomes there was no difference in survival or overall complication rates. There was no significant difference in quality of life scores and resource use between the groups. CONCLUSION: A randomised study of GDFT following liver transplantation is feasible. A post-trial stakeholder meeting supported proceeding with a full multi-centre trial.

Whole-body MRI compared with standard pathways for staging metastatic disease in lung and colorectal cancer: the Streamline diagnostic accuracy studies.

BACKGROUND: Whole-body magnetic resonance imaging is advocated as an alternative to standard pathways for staging cancer. OBJECTIVES: The objectives were to compare diagnostic accuracy, efficiency, patient acceptability, observer variability and cost-effectiveness of whole-body magnetic resonance imaging and standard pathways in staging newly diagnosed non-small-cell lung cancer (Streamline L) and colorectal cancer (Streamline C). DESIGN: The design was a prospective multicentre cohort study. SETTING: The setting was 16 NHS hospitals. PARTICIPANTS: Consecutive patients aged ≥ 18 years with histologically proven or suspected colorectal (Streamline C) or non-small-cell lung cancer (Streamline L). INTERVENTIONS: Whole-body magnetic resonance imaging. Standard staging investigations (e.g. computed tomography and positron emission tomography-computed tomography). REFERENCE STANDARD: Consensus panel decision using 12-month follow-up data. MAIN OUTCOME MEASURES: The primary outcome was per-patient sensitivity difference between whole-body magnetic resonance imaging and standard staging pathways for metastasis. Secondary outcomes included differences in specificity, the nature of the first major treatment decision, time and number of tests to complete staging, patient experience and cost-effectiveness. RESULTS: Streamline C - 299 participants were included. Per-patient sensitivity for metastatic disease was 67% (95% confidence interval 56% to 78%) and 63% (95% confidence interval 51% to 74%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -5% to 13%; p = 0.51). Specificity was 95% (95% confidence interval 92% to 97%) and 93% (95% confidence interval 90% to 96%) respectively, a difference of 2% (95% confidence interval -2% to 6%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 96% and 95% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 8 days (95% confidence interval 6 to 9 days) and 13 days (95% confidence interval 11 to 15 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 5 days (95% confidence interval 3 to 7 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £216 (95% confidence interval £211 to £221) versus £285 (95% confidence interval £260 to £310). Streamline L - 187 participants were included. Per-patient sensitivity for metastatic disease was 50% (95% confidence interval 37% to 63%) and 54% (95% confidence interval 41% to 67%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -7% to 15%; p = 0.73). Specificity was 93% (95% confidence interval 88% to 96%) and 95% (95% confidence interval 91% to 98%), respectively, a difference of 2% (95% confidence interval -2% to 7%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 98% and 99% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 13 days (95% confidence interval 12 to 14 days) and 19 days (95% confidence interval 17 to 21 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 6 days (95% confidence interval 4 to 8 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £317 (95% confidence interval £273 to £361) versus £620 (95% confidence interval £574 to £666). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most participants preferred the whole-body magnetic resonance imaging staging pathway if it reduced time to staging and/or number of tests. LIMITATIONS: Whole-body magnetic resonance imaging was interpreted by practitioners blinded to other clinical data, which may not fully reflect how it is used in clinical practice. CONCLUSIONS: In colorectal and non-small-cell lung cancer, the whole-body magnetic resonance imaging staging pathway has similar accuracy to standard staging pathways, is generally preferred by patients, improves staging efficiency and has lower staging costs. Future work should address the utility of whole-body magnetic resonance imaging for treatment response assessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43958015 and ISRCTN50436483. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 66. See the NIHR Journals Library website for further project information.

Colorectal and lung cancer are the leading causes of cancer-related deaths in the UK. Optimal treatment depends on accurately defining (or 'staging') the extent of disease, particularly if it has spread to other parts of the body such as the liver. Current staging pathways are complex and rely on a variety of tests that use X-rays, such as computed tomography and positron emission tomography­computed tomography scans. Patients often undergo multiple tests before starting treatment. Alternatively, it is possible to scan the whole body using magnetic resonance imaging without X-rays, and this may be more accurate and reduce the time and number of tests needed before treatment can start. We compared the ability to detect cancer spread, efficiency, patient experience and cost-effectiveness of staging based on whole-body magnetic resonance imaging with the standard NHS pathways in participants newly diagnosed with either lung (187 participants) or colorectal (299 participants) cancer. We found that the whole-body magnetic resonance imaging pathway was as accurate as standard staging pathways and resulted in very similar treatment decisions made by the clinical teams. The whole-body magnetic resonance imaging pathway detected 67% and 50% of participants with cancer spread in colorectal and lung cancer, respectively, compared with 63% and 54%, respectively, for standard staging. However, staging was quicker using whole-body magnetic resonance imaging (by 5 days for colorectal cancer and 6 days for lung cancer) and needed on average one less test to stage colorectal cancer. The whole-body magnetic resonance imaging pathway was also cheaper (costing on average £216 and £317 for colorectal and lung cancer, respectively, compared with £285 and £620, respectively, for standard pathways). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most preferred the whole-body magnetic resonance imaging pathway if it reduced the time to staging and/or the number of tests. Agreement between different radiology doctors interpreting the same whole-body magnetic resonance imaging scan was moderate for colon cancer and low for lung cancer, emphasising the need for training.

The prediction of suicide in severe mental illness: development and validation of a clinical prediction rule (OxMIS).

Assessment of suicide risk in individuals with severe mental illness is currently inconsistent, and based on clinical decision-making with or without tools developed for other purposes. We aimed to develop and validate a predictive model for suicide using data from linked population-based registers in individuals with severe mental illness. A national cohort of 75,158 Swedish individuals aged 15-65 with a diagnosis of severe mental illness (schizophrenia-spectrum disorders, and bipolar disorder) with 574,018 clinical patient episodes between 2001 and 2008, split into development (58,771 patients, 494 suicides) and external validation (16,387 patients, 139 suicides) samples. A multivariable derivation model was developed to determine the strength of pre-specified routinely collected socio-demographic and clinical risk factors, and then tested in external validation. We measured discrimination and calibration for prediction of suicide at 1 year using specified risk cut-offs. A 17-item clinical risk prediction model for suicide was developed and showed moderately good measures of discrimination (c-index 0.71) and calibration. For risk of suicide at 1 year, using a pre-specified 1% cut-off, sensitivity was 55% (95% confidence interval [CI] 47-63%) and specificity was 75% (95% CI 74-75%). Positive and negative predictive values were 2% and 99%, respectively. The model was used to generate a simple freely available web-based probability-based risk calculator (Oxford Mental Illness and Suicide tool or OxMIS) without categorical cut-offs. A scalable prediction score for suicide in individuals with severe mental illness is feasible. If validated in other samples and linked to effective interventions, using a probability score may assist clinical decision-making.

Urinary Neutrophil Gelatinase Associated Lipocalins (NGALs) predict acute kidney injury post liver transplant.

BACKGROUND: Acute Kidney Injury, a common complication of liver transplant, is associated with a significant increase in the risk of morbidity, mortality and graft loss. Current diagnostic criteria leaves a delay in diagnosis allowing further potential irreversible damage. Early biomarkers of renal injury are of clinical importance and Neutrophil Gelatinase Associated Lipocalins (NGALs) and Syndecan-1 were investigated. METHODS: AKI was defined according to the Acute Kidney Injury Network criteria. Urine and blood samples were collected pre-operatively, immediately post-op and 24 h post reperfusion to allow measurement of NGAL and Syndecan-1 levels. RESULTS: 13 of 27 patients developed an AKI. Patients who developed AKI had significantly higher peak transaminases. Urinary NGAL, plasma NGAL and Syndecan-1 levels were significantly elevated in all patients post reperfusion. Urinary NGAL levels immediately post-op were significantly higher in patients who developed an AKI than those that didn't [1319 ng/ml vs 46.56 ng/ml, p ≤ 0.001]. ROC curves were performed and urinary NGAL levels immediately post-op were an excellent biomarker for AKI with an area under the curve of 0.948 (0.847-1.00). CONCLUSIONS: Urinary NGAL levels measured immediately post-op accurately predict the development of AKI and their incorporation into clinical practise could allow early protocols to be developed to treat post transplant AKI.

A Clinical Feasibility Study of the Forensic Psychiatry and Violence Oxford (FoVOx) Tool.

Background: Risk assessment informs decisions around admission to and discharge from secure psychiatric hospital and contributes to treatment and supervision. There are advantages to using brief, scalable, free online tools with similar accuracy to instruments currently used. We undertook a study of one such risk assessment, the Forensic Psychiatry and Violence Oxford (FoVOx) tool, examining its acceptability, feasibility, and practicality. Methods: We completed the FoVOx tool on all discharges from six secure psychiatric hospitals in one region in England over two years. We interviewed 11 senior forensic psychiatrists regarding each discharge using a standardized questionnaire. Their patient's FoVOx score was compared to clinical risk assessment, and the senior clinicians were asked if they considered FoVOx scores accurate and useful. A modified thematic analysis was conducted, and clinicians were surveyed about current risk assessment practice on discharge. Results: Of 90 consecutive discharges, 84 were included in the final analysis. The median FoVOx probability score was 11% risk of violent recidivism in two years after discharge. We estimated that 12 (14%) individuals reoffended since discharge; all were in the medium or high risk FoVOx categories. Clinical assessment of risk agreed with the FoVOx categories in around half the cases. Clinicians were more likely to provide lower risk categories compared with FoVOx ones. FoVOx was considered to be an accurate representation of risk in 67% of cases; clinicians revised their view on some patient's risk assessment after being informed of their FoVOx scores. Completing FoVOx was reported to be helpful in the majority of cases. Reasons included improved communication with other agencies, reassurance to clinical teams, and identifying additional factors not fully considered. 10 of the 11 respondents reported that FoVOx was practical, and seven of 11 reported that they would use it in the future, highlighting its brevity and speed of use compared to existing risk assessment tools. Conclusions: Senior clinicians in this regional forensic psychiatric service found the FoVOx risk assessment tool feasible, practical, and easy to use. Its use addressed a lack of consistency around risk assessment at the point of discharge and, if used routinely, could assist in clinical decision-making.

Variation in the observed effect of Xpert MTB/RIF testing for tuberculosis on mortality: A systematic review and analysis of trial design considerations.

Background: Most studies evaluating the effect of Xpert MTB/RIF testing for tuberculosis (TB) concluded that it did not reduce overall mortality compared to usual care. We conducted a systematic review to assess whether key study design and execution features contributed to earlier identification of patients with TB and decreased pre-treatment loss to follow-up, thereby reducing the potential impact of Xpert MTB/RIF testing. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Scopus for literature published from 1 st January 2009 to February 2019. We included all primary intervention studies that had evaluated the effect of Xpert MTB/RIF on mortality compared to usual care in participants with presumptive pulmonary TB. We critically reviewed features of included studies across: Study setting and context, Study population, Participant recruitment and enrolment, Study procedures, and Study follow-up. Results: We included seven randomised and one non-randomised study.  All included studies demonstrated relative reductions in overall mortality in the Xpert MTB/RIF arm ranging from 6% to 40%. However, mortality reduction was reported to be statistically significant in two studies. Study features that could explain the lack of observed effect on mortality included: the higher quality of care at study sites; inclusion of patients with a higher pre-test probability of TB leading to higher than expected empirical rates; performance of additional diagnostic testing not done in usual care leading to increased TB diagnosis or empiric treatment initiation; the recruitment of participants likely to return for follow-up; and involvement of study staff in ensuring adherence with care and follow-up. Conclusion: Most studies of Xpert MTB/RIF were designed and conducted in a manner that resulted in more patients being diagnosed and treated for TB, minimising the potential difference in mortality Xpert MTB/RIF testing could have achieved compared to usual care.