Predictive value of S100-B and copeptin for outcomes following seizure: the BISTRO International Cohort Study.

OBJECTIVE: To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure. METHODS: We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days. RESULTS: Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 μg/l [95% CI 0.07-0.20] vs 0.09 μg/l [0.07-0.14]) and copeptin (23 pmol/l [9-104] vs 17 pmol/l [8-43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51-0.64] and 0.59 [0.54-0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1-1.5]), provoked seizure (OR 4.93 [2.5-9.8]), complex partial seizure (OR 4.09 [1.8-9.1]) and first seizure (OR 1.83 [1.1-3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80-18.9] copeptin OR 1 [1.00-1.00]). CONCLUSION: The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes

Diagnostic performances of S100-B and Copeptin, and 95% confidence interval.

<p>PPV, positive predictive value; NPV, negative predictive value; LR+, positive likelihood ratio; LR-, negative LR.</p><p>Diagnostic performances of S100-B and Copeptin, and 95% confidence interval.</p

Median of S100B and copeptin, with their 25%-75% interquartile range.

<p>ICU: Intensive Care Unit.</p><p>Median of S100B and copeptin, with their 25%-75% interquartile range.</p

Flow chart ED: emergency department.

<p>Composite endpoint of recurrence, hospitalization or death at day seven.</p

Outcomes and follow up of the study cohort.

<p>ED, emergency department, ICU, intensive care unit; IQR, 25–75% interquartile range.</p><p>Outcomes and follow up of the study cohort.</p

Characteristics of study cohort.

<p>SD, standard deviation; IQR, 25–75% interquartile range; ED, emergency department; GCS, Glasgow coma scale; WBC, white blood cells. All laboratory results were obtained from venous blood.</p><p>Characteristics of study cohort.</p

Receiving operator characteristics curve for Copeptin and S100B.

<p>Area under the curve 0.57 [95% CI 0.51–0.64] for S100B, p = 0.01, and 0.59 [95% CI 0.54–0.64] for copeptin, p = 0.02.</p

S100B and copeptin values in the two groups.

<p>Box plot with median, interquartile range, and 5^th and 95^th centile. Composite endpoint of recurrence, hospitalization or death at day seven.</p

Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients

International audienceImportance: The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial.Objective: To prospectively validate the safety of a PERC-based strategy to rule out PE.Design, setting, and patients: A crossover cluster-randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016.Interventions: Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative.Main outcomes and measures: The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission.Results: Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, -∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, -10% [95% CI, -13% to -6%]; P < .001). In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1% to 6.6%]).Conclusions and relevance: Among very low-risk patients with suspected PE, randomization to a PERC strategy vs conventional strategy did not result in an inferior rate of thromboembolic events over 3 months. These findings support the safety of PERC for very low-risk patients presenting to the emergency department.Trial registration: clinicaltrials.gov Identifier: NCT02375919