Prediction of violent crime on discharge from secure psychiatric hospitals: A clinical prediction rule (FoVOx).

BACKGROUND: Current approaches to assess violence risk in secure hospitals are resource intensive, limited by accuracy and authorship bias and may have reached a performance ceiling. This study seeks to develop scalable predictive models for violent offending following discharge from secure psychiatric hospitals. METHODS: We identified all patients discharged from secure hospitals in Sweden between January 1, 1992 and December 31, 2013. Using multiple Cox regression, pre-specified criminal, sociodemographic, and clinical risk factors were included in a model that was tested for discrimination and calibration in the prediction of violent crime at 12 and 24 months post-discharge. Risk cut-offs were pre-specified at 5% (low vs. medium) and 20% (medium vs. high). RESULTS: We identified 2248 patients with 2933 discharges into community settings. We developed a 12-item model with good measures of calibration and discrimination (area under the curve=0.77 at 12 and 24 months). At 24 months post-discharge, using the 5% cut-off, sensitivity was 96% and specificity was 21%. Positive and negative predictive values were 19% and 97%, respectively. Using the 20% cut-off, sensitivity was 55%, specificity 83% and the positive and negative predictive values were 37% and 91%, respectively. The model was used to develop a free online tool (FoVOx). INTERPRETATION: We have developed a prediction score in a Swedish cohort of patients discharged from secure hospitals that can assist in clinical decision-making. Scalable predictive models for violence risk are possible in specific patient groups and can free up clinical time for treatment and management. Further evaluation in other countries is needed. FUNDING: Wellcome Trust (202836/Z/16/Z) and the Swedish Research Council. The funding sources had no involvement in writing of the manuscript or decision to submit or in data collection, analysis or interpretation or any aspect pertinent to the study.

An empirical investigation into the role of subjective prior probability in searching for potentially missing items.

There are many examples from the scientific literature of visual search tasks in which the length, scope and success rate of the search have been shown to vary according to the searcher's expectations of whether the search target is likely to be present. This phenomenon has major practical implications, for instance in cancer screening, when the prevalence of the condition is low and the consequences of a missed disease diagnosis are severe. We consider this problem from an empirical Bayesian perspective to explain how the effect of a low prior probability, subjectively assessed by the searcher, might impact on the extent of the search. We show how the searcher's posterior probability that the target is present depends on the prior probability and the proportion of possible target locations already searched, and also consider the implications of imperfect search, when the probability of false-positive and false-negative decisions is non-zero. The theoretical results are applied to two studies of radiologists' visual assessment of pulmonary lesions on chest radiographs. Further application areas in diagnostic medicine and airport security are also discussed.

Giardiasis in North West England: faecal specimen requesting rates by GP practice.

Many cases of giardiasis in the UK are undiagnosed and among other things, diagnosis is dependent upon the readiness of GPs to request a specimen. The aim of this study is to assess the rate of specimens requested per GP practice in Central Lancashire, to examine the differences between GP practices and to estimate the pattern of unexplained spatial variation in the practice rate of specimens after adjustment for deprivation. To achieve this, we fitted a set of binomial and Poisson regression models, with random effects for GP practice. Our analysis suggests that there were differences in the rate of specimens by GP practices (P < 0·001) for a single year, but no difference in the proportion of positive tests per specimen submitted or in the rate of positive specimens per practice population. There was a difference in the cumulative rate of positive specimens per practice population over a 9-year period (P < 0·001). Neither the specimen rate per practice for a single year nor the cumulative rate of positive specimens over multiple years demonstrated significant spatial correlation. Hence, spatial variation in the incidence of giardiasis is unlikely to be confounded by variation in GP rate of specimens.

Towards a framework for analysis of eye-tracking studies in the three dimensional environment: a study of visual search by experienced readers of endoluminal CT colonography.

OBJECTIVE: Eye tracking in three dimensions is novel, but established descriptors derived from two-dimensional (2D) studies are not transferable. We aimed to develop metrics suitable for statistical comparison of eye-tracking data obtained from readers of three-dimensional (3D) "virtual" medical imaging, using CT colonography (CTC) as a typical example. METHODS: Ten experienced radiologists were eye tracked while observing eight 3D endoluminal CTC videos. Subsequently, we developed metrics that described their visual search patterns based on concepts derived from 2D gaze studies. Statistical methods were developed to allow analysis of the metrics. RESULTS: Eye tracking was possible for all readers. Visual dwell on the moving region of interest (ROI) was defined as pursuit of the moving object across multiple frames. Using this concept of pursuit, five categories of metrics were defined that allowed characterization of reader gaze behaviour. These were time to first pursuit, identification and assessment time, pursuit duration, ROI size and pursuit frequency. Additional subcategories allowed us to further characterize visual search between readers in the test population. CONCLUSION: We propose metrics for the characterization of visual search of 3D moving medical images. These metrics can be used to compare readers' visual search patterns and provide a reproducible framework for the analysis of gaze tracking in the 3D environment. ADVANCES IN KNOWLEDGE: This article describes a novel set of metrics that can be used to describe gaze behaviour when eye tracking readers during interpretation of 3D medical images. These metrics build on those established for 2D eye tracking and are applicable to increasingly common 3D medical image displays.

How much might cardiovascular disease risk be reduced by intensive therapy in people with screen-detected diabetes?

AIMS: To assess the cardiovascular disease (CVD) risk of people with screen-detected Type 2 diabetes and to estimate the risk reduction achievable through early intensive pharmacological intervention. METHODS: In ADDITION-Cambridge, diabetic patients were identified among people aged 40-69 years through a stepwise screening procedure including a risk score, random and fasting capillary blood glucose, HbA(1c) and oral glucose tolerance test. In those without prior macrovascular disease, 10-year CVD risk was computed using UK Prospective Diabetes Study (UKPDS) and Framingham engines. The absolute risk reduction achievable and its plausible range were predicted using relative risk reductions for individual therapies from published trials and sensitivity analysis. RESULTS: Of the 867 individuals with undiagnosed diabetes, 19% had pre-existing CVD, 97% were overweight or obese, 86% had hypertension, 75% had dyslipidaemia, 20% had microalbuminuria and 18% were smokers. Of those with hypertension, 35% were not prescribed drugs and 42% were suboptimally treated. Of participants with dyslipidaemia, 68% were not prescribed medications and 22% were poorly controlled. Median 10-year CVD risk was 34.0%[interquartile range (IQR) 26.2-44.6] in men and 21.5% (IQR 15.7-28.7) in women using the UKPDS engine; 38.6% (IQR 27.8-53.0) in men and 24.6% (IQR 17.2-32.9) in women using Framingham equations. In the most conservative scenario (no additive effect of therapies), the absolute risk reduction achievable through multifactorial therapy ranged from 4.9 to 9.5% (UKPDS) and from 5.4 to 10.5% (Framingham). The corresponding ranges of numbers needed to treat were 11-20 and 10-19. CONCLUSIONS: People with screen-detected diabetes have an adverse cardiovascular risk profile, which is potentially modifiable through application of existing treatment recommendations.

Comparison of risk-scoring methods in predicting the immediate outcome after elective open abdominal aortic aneurysm surgery.

BACKGROUND & OBJECTIVES: The aim of this study was to apply three simple risk - scoring systems to prospectively collected data on all elective open Abdominal Aortic Aneurysm (AAA) operations in the Cambridge Academic Vascular Unit over a 6 - year period (January 1998 to January 2004), to compare their predictive values and to evaluate their validity with respect to prediction of mortality and post-operative complications. METHODS: 204 patients underwent elective open infra-renal AAA repair. Data were prospectively collected and risk assessment scores were calculated for mortality and morbidity according to the Glasgow Aneurysm Score (GAS), VBHOM (Vascular Biochemistry and Haematology Outcome Models) and Estimation of Physiologic Ability and Surgical Stress (E-PASS). RESULTS: The mortality rate was 6.3% (13/204) and 59% (121/204) experienced a post-operative complication (30-day outcome). For GAS, VBHOM and E-PASS the receiver operating characteristics (ROC) curve analysis for prediction of in-hospital mortality showed area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.76 to 0.92; p<0.0001), 0.82 (95% CI, 0.68 to 0.95; p=0.0001) and 0.92 (95% CI, 0.87 to 0.97; p<0.0001) respectively. There were also significant correlations between post-operative complications and length of hospital stay and each of the three scores, but the correlation was substantially higher in the case of E-PASS. CONCLUSIONS: All three scoring systems accurately predicted the risk of mortality and morbidity in patients undergoing elective open AAA repair. Among these, E-PASS seemed to be the most accurate predictor in this patient population.

A randomized, controlled trial of routine early abdominal computed tomography in patients presenting with non-specific acute abdominal pain.

AIM: To compare the effect of an initial early computed tomography (CT) examination versus standard practice (SP) on the length of hospital stay, diagnostic accuracy, and mortality of adults presenting with acute abdominal pain. MATERIALS AND METHODS: Two hundred and five adults presenting with acute abdominal pain were randomized to undergo an early CT examination or current SP, which comprised supine abdominal and erect chest radiography. One hundred and ninety-eight patients (99 in each arm) were included in the analysis. The primary endpoint was the duration of inpatient stay; secondary endpoints were diagnostic certainty and mortality. RESULTS: There was no significant difference in the length of hospital stay between the two arms (p=0.20). At randomization 36% (35 of 96) of CT patients and 49% (48 of 98) of SP patients were correctly diagnosed; 24h after randomization the correct diagnosis had been established in 84% of CT patients and 73% of SP patients. This refinement in diagnostic certainty was significantly better in the CT group (p<0.001). There was no difference in mortality between the two trial arms (p=0.31). CONCLUSION: Early abdominal CT in patients with acute abdominal pain improves diagnostic certainty, but does not reduce the length of hospital stay and 6 month mortality.

The GRAIDS Trial: a cluster randomised controlled trial of computer decision support for the management of familial cancer risk in primary care.

The objective was to evaluate the effect of an assessment strategy using the computer decision support system (the GRAIDS software), on the management of familial cancer risk in British general practice in comparison with best current practice. The design included cluster randomised controlled trial, and involved forty-five general practice teams in East Anglia, UK. Randomised to GRAIDS (Genetic Risk Assessment on the Internet with Decision Support) support (intervention n=23) or comparison (n=22). Training in the new assessment strategy and access to the GRAIDS software (GRAIDS arm) was conducted, compared with an educational session and guidelines about managing familial breast and colorectal cancer risk (comparison) were mailed. Outcomes were measured at practice, practitioner and patient levels. The primary outcome measure, at practice level, was the proportion of referrals made to the Regional Genetics Clinic for familial breast or colorectal cancer that were consistent with referral guidelines. Other measures included practitioner confidence in managing familial cancer (GRAIDS arm only) and, in patients: cancer worry, risk perception and knowledge about familial cancer. There were more referrals to the Regional Genetics Clinic from GRAIDS than comparison practices (mean 6.2 and 3.2 referrals per 10 000 registered patients per year; mean difference 3.0 referrals; 95% confidence interval (CI) 1.2-4.8; P=0.001); referrals from GRAIDS practices were more likely to be consistent with referral guidelines (odds ratio (OR)=5.2; 95% CI 1.7-15.8, P=0.006). Patients referred from GRAIDS practices had lower cancer worry scores at the point of referral (mean difference -1.44 95% CI -2.64 to -0.23, P=0.02). There were no differences in patient knowledge about familial cancer. The intervention increased GPs' confidence in managing familial cancer. Compared with education and mailed guidelines, assessment including computer decision support increased the number and quality of referrals to the Regional Genetics Clinic for familial cancer risk, improved practitioner confidence and had no adverse psychological effects in patients. Trials are registered under N0181144343 in the UK National Research Register.

Transjugular liver biopsy in patients with diffuse liver disease: comparison of three cores with one or two cores for accurate histological interpretation.

BACKGROUND: Transjugular liver biopsy (TJLB) can be performed to obtain more than two cores safely. This advantage has not been evaluated in terms of diagnostic accuracy or grading/staging evaluation. AIM: To evaluate whether three separate cores of TJLB provide more histological information compared with two or one cores. METHODS: Twenty-three patients, who had three separate passes, with each core >/=7mm in length using a 19G Tru-cut needle, were evaluated. Each TJLB was blindly coded; the pathologist randomly assessed: (a) each core separately covering the other two, (b) two cores simultaneously covering the third and (c) the three cores together for diagnostic yield, inflammation and fibrosis. RESULTS: The mean TJLB length was 32+/-5.5mm. In 12 one-core (52%) and 18 2-core (78%) assessments, diagnosis (mainly cirrhosis) was made correctly in each core. The within-patient standard deviations for one-core vs two-core assessment were similar for grading (0.42 and 0.47, respectively), but higher for staging (0.39 and 0.15, respectively). Staging was underestimated in assessing one-core and less for two cores compared to three cores. CONCLUSION: Three non-fragmented cores (each core >/=7mm in length) of TJLB can be considered a minimum requirement for histological assessment, giving better reproducibility in diagnosis as well as for inflammation and fibrosis.

Mitogenic growth signalling, DNA replication licensing, and survival are linked in prostate cancer.

Activation of mitogen/extracellular-signal-regulated kinase kinase 5/extracellular signal-regulated kinase-5 (MEK5/ERK5) growth signalling is coupled to increased cell proliferation in prostate cancer (PCa). Dysregulation of the DNA replication licensing pathway, a critical step in growth control downstream of transduction signalling pathways, is associated with development of PCa. In this study we have investigated linkages between the MEK5/ERK5 pathway and DNA replication licensing during prostate carcinogenesis. The effects of increased MEK5/ERK5 signalling on the expression of replication licensing factors Mcm2 and geminin and the proliferation marker Ki67 were studied in an ecdysone-inducible system expressing a constitutively activated mutant of MEK5 in EcR293 cells and in stable ERK5 over-expressing PC3 clones. In parallel, expression of these biomarkers in PCa biopsy specimens (n=58) was studied and compared to clinicopathological parameters. In both in vitro systems induction of MEK5 expression resulted in increased levels of phosphorylated ERK5 and Mcm2, geminin and Ki67 proteins. In PCa specimens average Mcm2 expression was greater than Ki67 and geminin expression (median labelling index (LI) 36.7, 18.1, and 3.4% respectively), consistent with their differential expression according to growth status (P<0.0001). Mcm2, geminin and Ki67 expression were significantly associated with Gleason grade (P=0.0002, P=0.0003, P=0.004); however there was no link with T or M stage. There was a significant relationship between increasing ERK5 expression and increasing Mcm2 (P=0.003) and Ki67 (P=0.009) expression, with non-significant trends seen with increasing MEK5 expression. There were significant associations between Gleason grade and the number of cells traversing G1 phase (Ki67(LI)-geminin(LI); (P=0.001)), with high ERK5 levels associated with both an increase in replication licensed but non-cycling cells (Mcm2(LI)-Ki67(LI); (P=0.01)) and accelerated cell cycle progression (geminin(LI)/Ki67(LI); (P= 0.005)), all indicative of a shift towards increasing proliferative potential. While Mcm2 and Ki67 were both prognostic factors on univariate analysis, only Mcm2 remained an independent prognostic marker on multivariate analysis. Taken together, our data show that induction of MEK5/ERK5 signalling is linked to activation of the DNA replication licensing pathway in PCa, and that the strong prognostic value of MCM proteins may result from their function as relay stations coupling growth regulatory pathways to genome duplication.

DNA replication licensing and cell cycle kinetics of normal and neoplastic breast.

Mcm2-7 (MCM) proteins are part of the origin licensing machinery that regulates initiation of DNA replication. Geminin is a licensing repressor and prevents reinitiation of DNA replication during S-G2-M phase by blocking reloading of Mcm2-7 at replication origins. Here, we have analysed these replication licensing factors (RLFs) to determine whether the pathway becomes deregulated during mammary carcinogenesis, and have assessed their potential value as prognostic markers. Protein expression profiles were generated for Ki67, Mcm2, geminin, HER-2, ER and PR in a series of reduction mammoplasty (n=18) and breast cancer specimens (n=120), and compared to clinicopathological parameters. A large proportion of epithelial cells of the terminal duct lobular unit reside in a primed 'replication licensed' but not proliferating state. This state is characterised by Mcm2 expression and absence of Ki67 and the S/G2/M marker geminin. In breast cancers, increasing tumour grade is associated with increased Ki67, Mcm2 and geminin expression. The Mcm2/Ki67 ratio decreases through the grades, indicating a shift from a predominantly licensed state to an actively proliferating state. This shift is associated with an increase in the geminin/Ki67 ratio, signifying a shortening of G1 phase in breast cancer cells. Ki67, Mcm2 and the Mcm2/Ki67 ratio are statistically significantly associated with the Nottingham Prognostic Index (NPI), but geminin and the geminin/Ki67 ratio are not. Ki67, Mcm2 and Mcm2/Ki67 are highly correlated with one another, with Mcm2 being the single most important predictor of NPI score (P<0.001). However, only 12% of variation in NPI is explained by Mcm2, as the labelling index for this marker is approaching 100% for many of the high-grade tumours. The origin licensing phenotypes of normal breast and breast cancers therefore relate to their cellular differentiation status, and high-level MCM expression in more poorly differentiated tumours severely constrains their use as prognostic markers in breast cancer.