Predicting outcome in acute stroke with large vessel occlusion-application and validation of MR PREDICTS in the ESCAPE-NA1 population.

BACKGROUND: Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate the performance of a validated outcome prediction score. PATIENTS AND METHODS: MR PREDICTS is an outcome prediction tool based on a logistic regression model designed to predict the treatment benefit of endovascular treatment based on the MR CLEAN and HERMES populations. ESCAPE-NA1 is a randomized trial of nerinetide vs. placebo in patients with acute stroke and large vessel occlusion. We applied MR PREDICTS to patients in the control arm of ESCAPE-NA1. Model performance was assessed by calculating its discriminative ability and calibration. RESULTS: Overall, 556/1105 patients (50.3%) in the ESCAPE-NA1-trial were randomized to the control arm, 435/556 (78.2%) were treated within 6 h of symptom onset. Good outcome (modified Rankin scale 0-2) at 3 months was achieved in 275/435 patients (63.2%), the predicted probability of good outcome was 52.5%. Baseline characteristics were similar in the study and model derivation cohort except for age (ESCAPE-NA1: mean: 70 y vs. HERMES: 66 y), hypertension (72% vs. 57%), and collaterals (good collaterals, 15% vs. 44%). Compared to HERMES we observed higher rates of successful reperfusion (TICI 2b-3, ESCAPE-NA1: 87% vs. HERMES: 71%) and faster times from symptom onset to reperfusion (median: 201 min vs. 286 min). Model performance was good, indicated by a c-statistic of 0.76 (95%confidence interval: 0.71-0.81). CONCLUSION: Outcome-prediction using models created from HERMES data, based on information available in the emergency department underestimated the actual outcome in patients with acute ischemic stroke and large vessel occlusion receiving endovascular treatment despite overall good model performance, which might be explained by differences in quality of and time to reperfusion. These findings underline the importance of timely and successful reperfusion for functional outcomes in acute stroke patients.

Comparison of Prehospital Assessment by Paramedics and In-Hospital Assessment by Physicians in Suspected Stroke Patients: Results From 2 Prospective Cohort Studies.

BACKGROUND: It is unknown if ambulance paramedics adequately assess neurological deficits used for prehospital stroke scales to detect anterior large-vessel occlusions. We aimed to compare prehospital assessment of these stroke-related deficits by paramedics with in-hospital assessment by physicians. METHODS: We used data from 2 prospective cohort studies: the LPSS (Leiden Prehospital Stroke Study) and PRESTO study (Prehospital Triage of Patients With Suspected Stroke). In both studies, paramedics scored 9 neurological deficits in stroke code patients in the field. Trained physicians scored the National Institutes of Health Stroke Scale (NIHSS) at hospital presentation. Patients with transient ischemic attack were excluded because of the transient nature of symptoms. Spearman rank correlation coefficient (rs) was used to assess correlation between the total prehospital assessment score, defined as the sum of all prehospital items, and the total NIHSS score. Correlation, sensitivity and specificity were calculated for each prehospital item with the corresponding NIHSS item as reference. RESULTS: We included 2850 stroke code patients. Of these, 1528 had ischemic stroke, 243 intracranial hemorrhage, and 1079 stroke mimics. Correlation between the total prehospital assessment score and NIHSS score was strong (rs=0.70 [95% CI, 0.68-0.72]). Concerning individual items, prehospital assessment of arm (rs=0.68) and leg (rs=0.64) motor function correlated strongest with corresponding NIHSS items, and had highest sensitivity (arm 95%, leg 93%) and moderate specificity (arm 71%, leg 70%). Neglect (rs=0.31), abnormal speech (rs=0.50), and gaze deviation (rs=0.51) had weakest correlations. Neglect and gaze deviation had lowest sensitivity (52% and 66%) but high specificity (84% and 89%), while abnormal speech had high sensitivity (85%) but lowest specificity (65%). CONCLUSIONS: The overall prehospital assessment of stroke code patients correlates strongly with in-hospital assessment. Prehospital assessment of neglect, abnormal speech, and gaze deviation differed most from in-hospital assessment. Focused training on these deficits may improve prehospital triage.

Development and Validation of a Postprocedural Model to Predict Outcome After Endovascular Treatment for Ischemic Stroke.

Importance: Outcome prediction after endovascular treatment (EVT) for ischemic stroke is important to patients, family members, and physicians. Objective: To develop and validate a model based on preprocedural and postprocedural characteristics to predict functional outcome for individual patients after EVT. Design, Setting, and Participants: A prediction model was developed using individual patient data from 7 randomized clinical trials, performed between December 2010 and December 2014. The model was developed within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration and external validation in data from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry of patients treated in clinical practice between March 2014 and November 2017. Participants included patients from multiple centers throughout different countries in Europe, North America, East Asia, and Oceania (derivation cohort), and multiple centers in the Netherlands (validation cohort). Included were adult patients with a history of ischemic stroke from an intracranial large vessel occlusion in the anterior circulation who underwent EVT within 12 hours of symptom onset or last seen well. Data were last analyzed in July 2022. Main Outcome(s) and Measure(s): A total of 19 variables were assessed by multivariable ordinal regression to predict functional outcome (modified Rankin Scale [mRS] score) 90 days after EVT. Variables were routinely available 1 day after EVT. Akaike information criterion (AIC) was used to optimize model fit vs model complexity. Probabilities for functional independence (mRS 0-2) and survival (mRS 0-5) were derived from the ordinal model. Model performance was expressed with discrimination (C statistic) and calibration. Results: A total of 781 patients (median [IQR] age, 67 [57-76] years; 414 men [53%]) constituted the derivation cohort, and 3260 patients (median [IQR] age, 72 [61-80] years; 1684 men [52%]) composed the validation cohort. Nine variables were included in the model: age, baseline National Institutes of Health Stroke Scale (NIHSS) score, prestroke mRS score, history of diabetes, occlusion location, collateral score, reperfusion grade, NIHSS score at 24 hours, and symptomatic intracranial hemorrhage 24 hours after EVT. External validation in the MR CLEAN Registry showed excellent discriminative ability for functional independence (C statistic, 0.91; 95% CI, 0.90-0.92) and survival (0.89; 95% CI, 0.88-0.90). The proportion of functional independence in the MR CLEAN Registry was systematically higher than predicted by the model (41% vs 34%), whereas observed and predicted survival were similar (72% vs 75%). The model was updated and implemented for clinical use. Conclusion and relevance: The prognostic tool MR PREDICTS@24H can be applied 1 day after EVT to accurately predict functional outcome for individual patients at 90 days and to provide reliable outcome expectations and personalize follow-up and rehabilitation plans. It will need further validation and updating for contemporary patients.

Prehospital Stroke Triage: A Modeling Study on the Impact of Triage Tools in Different Regions.

BACKGROUND AND PURPOSE: Direct transportation to a thrombectomy-capable intervention center is beneficial for patients with ischemic stroke due to large vessel occlusion (LVO), but can delay intravenous thrombolytics (IVT). The aim of this modeling study was to estimate the effect of prehospital triage strategies on treatment delays and overtriage in different regions. METHODS: We used data from two prospective cohort studies in the Netherlands: the Leiden Prehospital Stroke Study and the PRESTO study. We included stroke code patients within 6 h from symptom onset. We modeled outcomes of Rapid Arterial oCclusion Evaluation (RACE) scale triage and triage with a personalized decision tool, using drip-and-ship as reference. Main outcomes were overtriage (stroke code patients incorrectly triaged to an intervention center), reduced delay to endovascular thrombectomy (EVT), and delay to IVT. RESULTS: We included 1798 stroke code patients from four ambulance regions. Per region, overtriage ranged from 1-13% (RACE triage) and 3-15% (personalized tool). Reduction of delay to EVT varied by region between 24 ± 5 min (n = 6) to 78 ± 3 (n = 2), while IVT delay increased with 5 (n = 5) to 15 min (n = 21) for non-LVO patients. The personalized tool reduced delay to EVT for more patients (25 ± 4 min [n = 8] to 49 ± 13 [n = 5]), while delaying IVT with 3-14 min (8-24 patients). In region C, most EVT patients were treated faster (reduction of delay to EVT 31 ± 6 min (n = 35), with RACE triage and the personalized tool. CONCLUSIONS: In this modeling study, we showed that prehospital triage reduced time to EVT without disproportionate IVT delay, compared to a drip-and-ship strategy. The effect of triage strategies and the associated overtriage varied between regions. Implementation of prehospital triage should therefore be considered on a regional level.

Systematic metareview of prediction studies demonstrates stable trends in bias and low PROBAST inter-rater agreement.

OBJECTIVES: To (1) explore trends of risk of bias (ROB) in prediction research over time following key methodological publications, using the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and (2) assess the inter-rater agreement of the PROBAST. STUDY DESIGN AND SETTING: PubMed and Web of Science were searched for reviews with extractable PROBAST scores on domain and signaling question (SQ) level. ROB trends were visually correlated with yearly citations of key publications. Inter-rater agreement was assessed using Cohen's Kappa. RESULTS: One hundred and thirty nine systematic reviews were included, of which 85 reviews (containing 2,477 single studies) on domain level and 54 reviews (containing 2,458 single studies) on SQ level. High ROB was prevalent, especially in the Analysis domain, and overall trends of ROB remained relatively stable over time. The inter-rater agreement was low, both on domain (Kappa 0.04-0.26) and SQ level (Kappa -0.14 to 0.49). CONCLUSION: Prediction model studies are at high ROB and time trends in ROB as assessed with the PROBAST remain relatively stable. These results might be explained by key publications having no influence on ROB or recency of key publications. Moreover, the trend may suffer from the low inter-rater agreement and ceiling effect of the PROBAST. The inter-rater agreement could potentially be improved by altering the PROBAST or providing training on how to apply the PROBAST.

Predicting respiratory failure and outcome in pediatric Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) has a highly variable clinical course and outcome as indicated by the risk of developing respiratory failure and residual inability to walk. Prognostic models as Erasmus GBS Respiratory Insufficiency Score (EGRIS) developed in adult patients are inaccurate in children. Our aim was to determine the prognostic factors of respiratory failure and inability to walk in children with GBS and to develop a new clinical prognostic model for individual patients (EGRIS-Kids). METHODS: A multicenter retrospective cohort study was performed using the data of children (younger than 18 years) fulfilling the diagnostic criteria for GBS from the NINDS. This study was performed in two independent cohorts from centers in Germany, Switzerland, Austria (N = 265, collected 1989-2002) and The Netherlands (N = 156, collected 1987-2016). The predicted main outcomes were occurrence of respiratory failure during the disease course and inability to walk independent at one year after diagnosis. RESULTS: In the combined cohort of 421 children, 79 (19%) required mechanical ventilation and one patient died. The EGRIS-kids was developed including: age, cranial nerve involvement and GBS disability score at admission, resulting in a 9 point score predicting risks of respiratory failure ranging from 4 to 50% (AUC = 0.71). A lower GBS disability score at nadir was the strongest predictor of recovery to independent walking (at one month: OR 0.43 95%CI 0.25-0.74). CONCLUSIONS: EGRIS-Kids and GBS disability score at admission accurately predict the risk of respiratory failure and inability to walk respectively in children with GBS, as tools to personalize the monitoring and treatment.

Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment: External Validation of Prediction Models.

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a severe complication of reperfusion therapy for ischemic stroke. Multiple models have been developed to predict sICH or intracranial hemorrhage (ICH) after reperfusion therapy. We provide an overview of published models and validate their ability to predict sICH in patients treated with endovascular treatment in daily clinical practice. METHODS: We conducted a systematic search to identify models either developed or validated to predict sICH or ICH after reperfusion therapy (intravenous thrombolysis and/or endovascular treatment) for ischemic stroke. Models were externally validated in the MR CLEAN Registry (n=3180; Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was sICH according to the Heidelberg Bleeding Classification. Model performance was evaluated with discrimination (c-statistic, ideally 1; a c-statistic below 0.7 is considered poor in discrimination) and calibration (slope, ideally 1, and intercept, ideally 0). RESULTS: We included 39 studies describing 40 models. The most frequently used predictors were baseline National Institutes of Health Stroke Scale (NIHSS; n=35), age (n=22), and glucose level (n=22). In the MR CLEAN Registry, sICH occurred in 188/3180 (5.9%) patients. Discrimination ranged from 0.51 (SPAN-100 [Stroke Prognostication Using Age and National Institutes of Health Stroke Scale]) to 0.61 (SITS-SICH [Safe Implementation of Treatments in Stroke Symptomatic Intracerebral Hemorrhage] and STARTING-SICH [STARTING Symptomatic Intracerebral Hemorrhage]). Best calibrated models were IST-3 (intercept, -0.15 [95% CI, -0.01 to -0.31]; slope, 0.80 [95% CI, 0.50-1.09]), SITS-SICH (intercept, 0.15 [95% CI, -0.01 to 0.30]; slope, 0.62 [95% CI, 0.38-0.87]), and STARTING-SICH (intercept, -0.03 [95% CI, -0.19 to 0.12]; slope, 0.56 [95% CI, 0.35-0.76]). CONCLUSIONS: The investigated models to predict sICH or ICH discriminate poorly between patients with a low and high risk of sICH after endovascular treatment in daily clinical practice and are, therefore, not clinically useful for this patient population.

Biphasic Allergic Reactions at a Dutch Emergency Department: A 5-Year Retrospective Cohort Study.

BACKGROUND: A biphasic allergic reaction develops in 0.4-20% of patients with an allergic reaction, but the incidence of severe biphasic reactions is unknown OBJECTIVE: Our objective was to assess the incidence and time of onset of clinically relevant biphasic reactions in a Dutch emergency department (ED) cohort. Furthermore, the characteristics of patients with a biphasic reaction and the mean observation time after an allergy-related ED visit were assessed. METHODS: This was a single-center retrospective cohort study. We collected data from clinical records of adult patients presenting with an allergic reaction to the ED between January 2015 and December 2019. We defined clinically relevant biphasic reactions as biphasic reactions in which the criteria for anaphylaxis were met. RESULTS: Five hundred fifty-seven patients were included. Eight patients (1.4%) developed a biphasic reaction, of which 1 (0.2% of the total inclusions) was clinically relevant. In the subgroup of patients with an anaphylactic reaction (n = 258), those percentages were 2.3% and 0.4%, respectively. The mean time between the initial allergic reaction and the biphasic allergic reaction was 25.4 h (95% CI 13.2-37.6 h). The single clinically relevant biphasic reaction occurred 30 h after the initial reaction. CONCLUSIONS: The incidence of clinically relevant biphasic reactions in our cohort was low, with a mean time between the initial allergic reaction and the biphasic reaction of > 24 h. Based on these single-center retrospective data, routine inpatient monitoring for several hours does not seem warranted for all patients.

Evaluating the Diagnostic Performance of Prehospital Stroke Scales Across the Range of Deficit Severity: Analysis of the Prehospital Triage of Patients With Suspected Stroke Study.

BACKGROUND: The usefulness of prehospital scales for identifying anterior circulation large vessel occlusion (aLVO) in patients with suspected stroke may vary depending on the severity of their presentation. The performance of these scales across the spectrum of deficit severity is unclear. The aim of this study was to evaluate the diagnostic performance of 8 prehospital scales for identifying aLVO across the spectrum of deficit severity. METHODS: We used data from the PRESTO study (Prehospital Triage of Patients With Suspected Stroke Symptoms), a prospective observational study comparing prehospital stroke scales in detecting aLVO in suspected stroke patients. We used the National Institutes of Health Stroke Scale (NIHSS) score, assessed in-hospital, as a proxy for the Clinical Global Impression of stroke severity during prehospital assessment by paramedics. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and the difference in aLVO probabilities with a positive or negative prehospital scale test (ΔPaLVO) for each scale for mild (NIHSS 0-4), intermediate (NIHSS 5-9), moderate (NIHSS 10-14), and severe deficits (NIHSS≥15). RESULTS: Among 1033 patients with suspected stroke, 119 (11.5%) had an aLVO, of whom 19 (16.0%) had mild, 25 (21.0%) had intermediate, 30 (25.2%) had moderate, and 45 (37.8%) had severe deficits. The scales had low sensitivity and positive predictive value in patients with mild-intermediate deficits, and poor specificity, negative predictive value, and accuracy with moderate-severe deficits. Positive results achieved the highest ΔPaLVO in patients with mild deficits. Negative results achieved the highest ΔPaLVO with severe deficits, but the probability of aLVO with a negative result in the severe range was higher than with a positive test in the mild range. CONCLUSIONS: Commonly-used prehospital stroke scales show variable performance across the range of deficit severity. Probability of aLVO remains high with a negative test in severely affected patients. Studies reporting prehospital stroke scale performance should be appraised in the context of the NIHSS distribution of their samples.

Medical attention seeking by suspected stroke patients: Emergency medical services or general practitioner?

OBJECTIVE: Awareness campaigns advise the public to call emergency medical services (EMS) directly in case of suspected stroke. We aimed to explore patient and notification characteristics that influence direct EMS notification, the time to alert, and the time to treatment. METHODS: We performed a secondary analysis with data from the PRESTO study, a multi-center prospective observational cohort study that included patients with suspected stroke. We used multivariable binary logistic regression analyses to assess the association with direct EMS notification and multivariable linear regression analyses to assess the association with the onset-to-alert time, onset-to-needle time and onset-to-groin time. RESULTS: Of 436 included patients, 208 patients (48%) contacted EMS directly. FAST scores (aOR 1.45 for every point increase, 95%CI: 1.14-1.86), alert outside office hours (aOR 1.64 [1.05-2.55]), and onset-to-alert time (aOR for every minute less [≤55 min]: 0.96 [0.95-0.97]) were independently associated with direct EMS notification. Direct EMS call was independently associated with shorter onset-to-alert times (27 min [54-0.84]) and with shorter onset-to-needle times (-30 min [-51 to -10]). The association between direct EMS call and the onset-to-groin time was almost similar to the association with onset-to-needle time, though not statistically significant (univariable analysis: 23.7 min decrease [-103.7 to 56.2]). CONCLUSION: More than half of all patients with suspected stroke do not call EMS directly but call their GP instead. Patients with higher FAST scores, alert outside office hours, and a rapid alert, more often call EMS directly. Patients who call EMS directly are treated with IVT 30 min faster than patients who call the GP first. TRIAL REGISTRATION NUMBER: Netherlands Trial Register: NL7387, (www.trialregister.nl).

Outcome Prediction Models for Endovascular Treatment of Ischemic Stroke: Systematic Review and External Validation.

BACKGROUND AND PURPOSE: Prediction models for outcome of patients with acute ischemic stroke who will undergo endovascular treatment have been developed to improve patient management. The aim of the current study is to provide an overview of preintervention models for functional outcome after endovascular treatment and to validate these models with data from daily clinical practice. METHODS: We systematically searched within Medline, Embase, Cochrane, Web of Science, to include prediction models. Models identified from the search were validated in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) registry, which includes all patients treated with endovascular treatment within 6.5 hours after stroke onset in the Netherlands between March 2014 and November 2017. Predictive performance was evaluated according to discrimination (area under the curve) and calibration (slope and intercept of the calibration curve). Good functional outcome was defined as a score of 0-2 or 0-3 on the modified Rankin Scale depending on the model. RESULTS: After screening 3468 publications, 19 models were included in this validation. Variables included in the models mainly addressed clinical and imaging characteristics at baseline. In the validation cohort of 3156 patients, discriminative performance ranged from 0.61 (SPAN-100 [Stroke Prognostication Using Age and NIH Stroke Scale]) to 0.80 (MR PREDICTS). Best-calibrated models were THRIVE (The Totaled Health Risks in Vascular Events; intercept -0.06 [95% CI, -0.14 to 0.02]; slope 0.84 [95% CI, 0.75-0.95]), THRIVE-c (intercept 0.08 [95% CI, -0.02 to 0.17]; slope 0.71 [95% CI, 0.65-0.77]), Stroke Checkerboard score (intercept -0.05 [95% CI, -0.13 to 0.03]; slope 0.97 [95% CI, 0.88-1.08]), and MR PREDICTS (intercept 0.43 [95% CI, 0.33-0.52]; slope 0.93 [95% CI, 0.85-1.01]). CONCLUSIONS: The THRIVE-c score and MR PREDICTS both showed a good combination of discrimination and calibration and were, therefore, superior in predicting functional outcome for patients with ischemic stroke after endovascular treatment within 6.5 hours. Since models used different predictors and several models had relatively good predictive performance, the decision on which model to use in practice may also depend on simplicity of the model, data availability, and the comparability of the population and setting.

Major stoma related morbidity in young children following stoma formation and closure: A retrospective cohort study.

BACKGROUND: Little is known about stoma related morbidity in young children. Therefore, the aim of this study is to assess major morbidity after stoma formation and stoma closure and its associated risk factors. METHODS: All consecutive young children (age ≤ three years) who received a stoma between 1998 and 2018 at our tertiary referral center were retrospectively included. The incidence of major stoma related morbidity (Clavien-Dindo grade ≥III) was the primary outcome. This was separately analysed for stoma formation alone, stoma closure alone and all stoma interventions combined. Non-stoma related morbidity was excluded. Risk factors for major morbidity were identified using multivariable logistic regression analysis. RESULTS: In total 336 young children were included with a median follow-up of 6 (IQR:2-11) years. Of these young children, 5% (n = 17/336) received a jejunostomy, 57% (n = 192/336) an ileostomy, and 38% (n = 127/336) a colostomy. Following stoma formation, 27% (n = 92/336) of the young children experienced major stoma related morbidity, mainly consisting of high output stoma, prolapse and stoma stenosis. The major morbidity rate was 23% (n = 66/292) following stoma closure, most commonly comprising anastomotic leakage/stenosis, incisional hernia and adhesive obstructions. For combined stoma interventions, major stoma related morbidity was 39% (n = 130/336). Ileostomy was independently associated with a higher risk of developing major morbidity following stoma formation (OR:2.5; 95%-CI:1.3-4.7) as well as following closure (OR:2.7; 95%-CI:1.3-5.8). CONCLUSIONS: Major stoma related morbidity is a frequent and severe clinical problem in young children, both after stoma formation and closure. The risk of morbidity should be considered when deliberating a stoma.

Primary versus early secondary referral to a specialized neurotrauma center in patients with moderate/severe traumatic brain injury: a CENTER TBI study.

BACKGROUND: Prehospital care for patients with traumatic brain injury (TBI) varies with some emergency medical systems recommending direct transport of patients with moderate to severe TBI to hospitals with specialist neurotrauma care (SNCs). The aim of this study is to assess variation in levels of early secondary referral within European SNCs and to compare the outcomes of directly admitted and secondarily transferred patients. METHODS: Patients with moderate and severe TBI (Glasgow Coma Scale < 13) from the prospective European CENTER-TBI study were included in this study. All participating hospitals were specialist neuroscience centers. First, adjusted between-country differences were analysed using random effects logistic regression where early secondary referral was the dependent variable, and a random intercept for country was included. Second, the adjusted effect of early secondary referral on survival to hospital discharge and functional outcome [6 months Glasgow Outcome Scale Extended (GOSE)] was estimated using logistic and ordinal mixed effects models, respectively. RESULTS: A total of 1347 moderate/severe TBI patients from 53 SNCs in 18 European countries were included. Of these 1347 patients, 195 (14.5%) were admitted after early secondary referral. Secondarily referred moderate/severe TBI patients presented more often with a CT abnormality: mass lesion (52% vs. 34%), midline shift (54% vs. 36%) and acute subdural hematoma (77% vs. 65%). After adjusting for case-mix, there was a large European variation in early secondary referral, with a median OR of 1.69 between countries. Early secondary referral was not associated with functional outcome (adjusted OR 1.07, 95% CI 0.78-1.69), nor with survival at discharge (1.05, 0.58-1.90). CONCLUSIONS: Across Europe, substantial practice variation exists in the proportion of secondarily referred TBI patients at SNCs that is not explained by case mix. Within SNCs early secondary referral does not seem to impact functional outcome and survival after stabilisation in a non-specialised hospital. Future research should identify which patients with TBI truly benefit from direct transportation.

External Validations of Cardiovascular Clinical Prediction Models: A Large-Scale Review of the Literature.

BACKGROUND: There are many clinical prediction models (CPMs) available to inform treatment decisions for patients with cardiovascular disease. However, the extent to which they have been externally tested, and how well they generally perform has not been broadly evaluated. METHODS: A SCOPUS citation search was run on March 22, 2017 to identify external validations of cardiovascular CPMs in the Tufts Predictive Analytics and Comparative Effectiveness CPM Registry. We assessed the extent of external validation, performance heterogeneity across databases, and explored factors associated with model performance, including a global assessment of the clinical relatedness between the derivation and validation data. RESULTS: We identified 2030 external validations of 1382 CPMs. Eight hundred seven (58%) of the CPMs in the Registry have never been externally validated. On average, there were 1.5 validations per CPM (range, 0-94). The median external validation area under the receiver operating characteristic curve was 0.73 (25th-75th percentile [interquartile range (IQR)], 0.66-0.79), representing a median percent decrease in discrimination of -11.1% (IQR, -32.4% to +2.7%) compared with performance on derivation data. 81% (n=1333) of validations reporting area under the receiver operating characteristic curve showed discrimination below that reported in the derivation dataset. 53% (n=983) of the validations report some measure of CPM calibration. For CPMs evaluated more than once, there was typically a large range of performance. Of 1702 validations classified by relatedness, the percent change in discrimination was -3.7% (IQR, -13.2 to 3.1) for closely related validations (n=123), -9.0 (IQR, -27.6 to 3.9) for related validations (n=862), and -17.2% (IQR, -42.3 to 0) for distantly related validations (n=717; P<0.001). CONCLUSIONS: Many published cardiovascular CPMs have never been externally validated, and for those that have, apparent performance during development is often overly optimistic. A single external validation appears insufficient to broadly understand the performance heterogeneity across different settings.

Sensitivity of prehospital stroke scales for different intracranial large vessel occlusion locations.

INTRODUCTION: Prehospital stroke scales have been proposed to identify stroke patients with a large vessel occlusion to allow direct transport to an intervention centre capable of endovascular treatment (EVT). It is unclear whether these scales are able to detect not only proximal, but also more distal treatable occlusions. Our aim was to assess the sensitivity of prehospital stroke scales for different EVT-eligible occlusion locations in the anterior circulation. PATIENTS AND METHODS: The MR CLEAN Registry is a prospective, observational study in all centres that perform EVT in the Netherlands. We included adult patients with an anterior circulation stroke treated between March 2014 and November 2017. We used National Institutes of Health Stroke Scale scores at admission to reconstruct previously published prehospital stroke scales. We compared the sensitivity of each scale for different occlusion locations. Occlusions were assessed with CT angiography by an imaging core laboratory blinded to clinical findings. RESULTS: We included 3021 patients for the analysis of 14 scales. All scales had the highest sensitivity to detect internal carotid artery terminus occlusions (ranging from 0.21 to 0.97) and lowest for occlusions of the M2 segment (0.08 to 0.84, p-values < 0.001).Discussion and conclusion: Although prehospital stroke scales are generally sensitive for proximal large vessel occlusions, they are less sensitive to detect more distal occlusions.

Prediction of Outcome and Endovascular Treatment Benefit: Validation and Update of the MR PREDICTS Decision Tool.

Background and Purpose: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice. Methods: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0­2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic. Results: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72­0.77) in HERMES and, after model updating, 0.80 (0.78­0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%­14.4%). Patients with low (<1%) predicted treatment benefit (n=135/3156 [4.3%]) had low rates of functional independence, irrespective of reperfusion status, suggesting potential absence of treatment benefit. The updated model was made available online for clinicians and researchers at www.mrpredicts.com. Conclusions: Because of the substantial treatment effect and small potential harm of EVT, most patients arriving within 6 hours at an endovascular-capable center should be treated regardless of their clinical characteristics. MR PREDICTS can be used to support clinical judgement when there is uncertainty about the treatment indication, when resources are limited, or before a patient is to be transferred to an endovascular-capable center.

Large-scale validation of the prediction model risk of bias assessment Tool (PROBAST) using a short form: high risk of bias models show poorer discrimination.

OBJECTIVE: To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at external validation. STUDY DESIGN AND SETTING: We evaluated risk of bias (ROB) on 102 CPMs from the Tufts CPM Registry, comparing PROBAST to a short form consisting of six PROBAST items anticipated to best identify high ROB. We then applied the short form to all CPMs in the Registry with at least 1 validation (n=556) and assessed the change in discrimination (dAUC) in external validation cohorts (n=1,147). RESULTS: PROBAST classified 98/102 CPMS as high ROB. The short form identified 96 of these 98 as high ROB (98% sensitivity), with perfect specificity. In the full CPM registry, 527 of 556 CPMs (95%) were classified as high ROB, 20 (3.6%) low ROB, and 9 (1.6%) unclear ROB. Only one model with unclear ROB was reclassified to high ROB after full PROBAST assessment of all low and unclear ROB models. Median change in discrimination was significantly smaller in low ROB models (dAUC -0.9%, IQR -6.2-4.2%) compared to high ROB models (dAUC -11.7%, IQR -33.3-2.6%; P<0.001). CONCLUSION: High ROB is pervasive among published CPMs. It is associated with poor discriminative performance at validation, supporting the application of PROBAST or a shorter version in CPM reviews.

Music intervention for sleep quality in critically ill and surgical patients: a meta-analysis.

OBJECTIVE: Sleep disruption occurs frequently in hospitalised patients. Given the potential of music intervention as a non-pharmacological measure to improve sleep quality, we aimed to assess and quantify current literature on the effect of recorded music interventions on sleep quality and quantity in the adult critical care and surgical populations. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, MEDLINE Ovid, Cochrane Central, Web of Science and Google Scholar. ELIGIBILITY CRITERIA FOR STUDIES: Randomised controlled trials assessing the effect of music on sleep quality in critically ill and surgical patients. METHODS: The electronic databases were systematically searched from 1 January 1981 to 27 January 2020. Data were screened, extracted and appraised by two independent reviewers. Primary outcomes were sleep quality and quantity, assessed with validated tools. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Random effects meta-analysis was performed, and pooled standardised mean differences (SMDs) with 95% CIs were reported. RESULTS: Five studies (259 patients) were included in qualitative (risk of bias) and quantitative analysis (meta-analysis). Pooled data showed a significant effect of recorded music on subjective sleep quality in the critical care and surgical population (SMD=1.21 (95% CI 0.50 to 1.91), p<0.01, excluding one non-English study; SMD=0.87 (95% CI 0.45 to 1.29), p<0.01). The SMD of 1.21 corresponded to a 27.1% (95% CI 11.2 to 42.8) increase in subjective sleep quality using validated questionnaires. A significant increase in subjective sleep quantity of 36 min was found in one study. Objective measurements of sleep assessed in one study using polysomnography showed significant increase in deeper sleep stage in the music group. CONCLUSIONS: Recorded music showed a significant improvement in subjective sleep quality in some critical care and surgical populations. Therefore, its use may be relevant to improve sleep, but given the moderate potential for bias, further research is needed. PROSPERO REGISTRATION NUMBER: CRD42020167783.

The Relationship between Hospital Volume and In-Hospital Mortality of Severely Injured Patients in Dutch Level-1 Trauma Centers.

Centralization of trauma centers leads to a higher hospital volume of severely injured patients (Injury Severity Score (ISS) > 15), but the effect of volume on outcome remains unclear. The aim of this study was to determine the association between hospital volume of severely injured patients and in-hospital mortality in Dutch Level-1 trauma centers. A retrospective observational cohort study was performed using the Dutch trauma registry. All severely injured adults (ISS > 15) admitted to a Level-1 trauma center between 2015 and 2018 were included. The effect of hospital volume on in-hospital mortality was analyzed with random effects logistic regression models with a random intercept for Level-1 trauma center, adjusted for important demographic and injury characteristics. A total of 11,917 severely injured patients from 13 Dutch Level-1 trauma centers was included in this study. Hospital volume varied from 120 to 410 severely injured patients per year. Observed mortality rates varied between 12% and 24% per center. After case-mix correction, no statistically significant differences between low- and high-volume centers were demonstrated (adjusted odds ratio 0.97 per 50 extra patients per year, 95% Confidence Interval 0.90-1.04, p = 0.44). The variation in hospital volume of the included Level-1 trauma centers was not associated with the outcome of severely injured patients. Our results suggest that well-organized trauma centers with a similar organization of care could potentially achieve comparable outcomes.