Performance of externally validated enhanced computer-aided versions of the National Early Warning Score in predicting mortality following an emergency admission to hospital in England: a cross-sectional study

Objectives: In the English National Health Service, the patient’s vital signs are monitored and summarised into a National Early Warning Score (NEWS) to support clinical decision making, but it does not provide an estimate of the patient’s risk of death. We examine the extent to which the accuracy of NEWS for predicting mortality could be improved by enhanced computer versions of NEWS (cNEWS). Design: Logistic regression model development and external validation study. Setting: Two acute hospitals (YH—York Hospital for model development; NH—Northern Lincolnshire and Goole Hospital for external model validation). Participants: Adult (≥16 years) medical admissions discharged over a 24-month period with electronic NEWS (eNEWS) recorded on admission are used to predict mortality at four time points (in-hospital, 24 hours, 48 hours and 72 hours) using the first electronically recorded NEWS (model M0) versus a cNEWS model which included age+sex (model M1) +subcomponents of NEWS (including diastolic blood pressure) (model M2). Results: The risk of dying in-hospital following emergency medical admission was 5.8% (YH: 2080/35 807) and 5.4% (NH: 1900/35 161). The c-statistics for model M2 in YH for predicting mortality (in-hospital=0.82, 24 hours=0.91, 48 hours=0.88 and 72 hours=0.88) was higher than model M0 (in-hospital=0.74, 24 hours=0.89, 48 hours=0.86 and 72 hours=0.85) with higher Positive Predictive Value (PPVs) for in-hospital mortality (M2 19.3% and M0 16.6%). Similar findings were seen in NH. Model M2 performed better than M0 in almost all major disease subgroups.Conclusions: An externally validated enhanced computer-aided NEWS model (cNEWS) incrementally improves on the performance of a NEWS only model. Since cNEWS places no additional data collection burden on clinicians and is readily automated, it may now be carefully introduced and evaluated to determine if it can improve care in hospitals that have eNEWS systems

Development and validation of a novel computer-aided score to predict the risk of in-hospital mortality for acutely ill medical admissions in two acute hospitals using their first electronically recorded blood test results and vital signs: A cross-section

Objectives There are no established mortality risk equations specifically for emergency medical patients who are admitted to a general hospital ward. Such risk equations may be useful in supporting the clinical decision-making process. We aim to develop and externally validate a computer-aided risk of mortality (CARM) score by combining the first electronically recorded vital signs and blood test results for emergency medical admissions.Design Logistic regression model development and external validation study.Setting Two acute hospitals (Northern Lincolnshire and Goole NHS Foundation Trust Hospital (NH)—model development data; York Hospital (YH)—external validation data).Participants Adult (aged ≥16 years) medical admissions discharged over a 24-month period with electronic National Early Warning Score(s) and blood test results recorded on admission.Results The risk of in-hospital mortality following emergency medical admission was 5.7% (NH: 1766/30 996) and 6.5% (YH: 1703/26 247). The C-statistic for the CARM score in NH was 0.87 (95% CI 0.86 to 0.88) and was similar in an external hospital setting YH (0.86, 95% CI 0.85 to 0.87) and the calibration slope included 1 (0.97, 95% CI 0.94 to 1.00).Conclusions We have developed a novel, externally validated CARM score with good performance characteristics for estimating the risk of in-hospital mortality following an emergency medical admission using the patient’s first, electronically recorded, vital signs and blood test results. Since the CARM score places no additional data collection burden on clinicians and is readily automated, it may now be carefully introduced and evaluated in hospitals with sufficient informatics infrastructure

A comparison of logistic regression models with alternative machine learning methods to predict the risk of in-hospital mortality in emergency medical admissions via external validation

YesWe compare the performance of logistic regression with several alternative machine learning methods to estimate the risk of death for patients following an emergency admission to hospital based on the patients’ first blood test results and physiological measurements using an external validation approach. We trained and tested each model using data from one hospital (n=24696) and compared the performance of these models in data from another hospital (n=13477). We used two performance measures – the calibration slope and area under the curve (AUC). The logistic model performed reasonably well – calibration slope 0.90, AUC 0.847 compared to the other machine learning methods. Given the complexity of choosing tuning parameters of these methods, the performance of logistic regression with transformations for in-hospital mortality prediction was competitive with the best performing alternative machine learning methods with no evidence of overfitting.Health Foundation; National Institute for Health Research (NIHR) Yorkshire and Humberside Patient Safety Translational Research Centre (NIHR YHPSTRC

Accelerated Evolution of the Prdm9 Speciation Gene across Diverse Metazoan Taxa

The onset of prezygotic and postzygotic barriers to gene flow between populations is a hallmark of speciation. One of the earliest postzygotic isolating barriers to arise between incipient species is the sterility of the heterogametic sex in interspecies' hybrids. Four genes that underlie hybrid sterility have been identified in animals: Odysseus, JYalpha, and Overdrive in Drosophila and Prdm9 (Meisetz) in mice. Mouse Prdm9 encodes a protein with a KRAB motif, a histone methyltransferase domain and several zinc fingers. The difference of a single zinc finger distinguishes Prdm9 alleles that cause hybrid sterility from those that do not. We find that concerted evolution and positive selection have rapidly altered the number and sequence of Prdm9 zinc fingers across 13 rodent genomes. The patterns of positive selection in Prdm9 zinc fingers imply that rapid evolution has acted on the interface between the Prdm9 protein and the DNA sequences to which it binds. Similar patterns are apparent for Prdm9 zinc fingers for diverse metazoans, including primates. Indeed, allelic variation at the DNA–binding positions of human PRDM9 zinc fingers show significant association with decreased risk of infertility. Prdm9 thus plays a role in determining male sterility both between species (mouse) and within species (human). The recurrent episodes of positive selection acting on Prdm9 suggest that the DNA sequences to which it binds must also be evolving rapidly. Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis. We propose a hypothetical model in which incompatibilities between Prdm9-binding specificity and satellite DNAs provide the molecular basis for Prdm9-mediated hybrid sterility. We suggest that Prdm9 should be investigated as a candidate gene in other instances of hybrid sterility in metazoans

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Embolization of Brain Arteriovenous Malformations With Versus Without Onyx Before Stereotactic Radiosurgery

Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates. To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study. We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes. The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar. Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention

Stereotactic radiosurgery with versus without prior Onyx embolization for brain arteriovenous malformations

OBJECTIVE: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the pre-embolized nidus. METHODS: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. RESULTS: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively. CONCLUSIONS: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs