Ten (not so) simple rules for clinical trial data-sharing.

Clinical trial data-sharing is seen as an imperative for research integrity and is becoming increasingly encouraged or even required by funders, journals, and other stakeholders. However, early experiences with data-sharing have been disappointing because they are not always conducted properly. Health data is indeed sensitive and not always easy to share in a responsible way. We propose 10 rules for researchers wishing to share their data. These rules cover the majority of elements to be considered in order to start the commendable process of clinical trial data-sharing: Rule 1: Abide by local legal and regulatory data protection requirementsRule 2: Anticipate the possibility of clinical trial data-sharing before obtaining fundingRule 3: Declare your intent to share data in the registration stepRule 4: Involve research participantsRule 5: Determine the method of data accessRule 6: Remember there are several other elements to shareRule 7: Do not proceed aloneRule 8: Deploy optimal data management to ensure that the data shared is usefulRule 9: Minimize risksRule 10: Strive for excellence.

Social Determinants of Health and Limitation of Life-Sustaining Therapy in Neurocritical Care: A CHoRUS Pilot Project.

BACKGROUND: Social determinants of health (SDOH) have been linked to neurocritical care outcomes. We sought to examine the extent to which SDOH explain differences in decisions regarding life-sustaining therapy, a key outcome determinant. We specifically investigated the association of a patient's home geography, individual-level SDOH, and neighborhood-level SDOH with subsequent early limitation of life-sustaining therapy (eLLST) and early withdrawal of life-sustaining therapy (eWLST), adjusting for admission severity. METHODS: We developed unique methods within the Bridge to Artificial Intelligence for Clinical Care (Bridge2AI for Clinical Care) Collaborative Hospital Repository Uniting Standards for Equitable Artificial Intelligence (CHoRUS) program to extract individual-level SDOH from electronic health records and neighborhood-level SDOH from privacy-preserving geomapping. We piloted these methods to a 7 years retrospective cohort of consecutive neuroscience intensive care unit admissions (2016-2022) at two large academic medical centers within an eastern Massachusetts health care system, examining associations between home census tract and subsequent occurrence of eLLST and eWLST. We matched contextual neighborhood-level SDOH information to each census tract using public data sets, quantifying Social Vulnerability Index overall scores and subscores. We examined the association of individual-level SDOH and neighborhood-level SDOH with subsequent eLLST and eWLST through geographic, logistic, and machine learning models, adjusting for admission severity using admission Glasgow Coma Scale scores and disorders of consciousness grades. RESULTS: Among 20,660 neuroscience intensive care unit admissions (18,780 unique patients), eLLST and eWLST varied geographically and were independently associated with individual-level SDOH and neighborhood-level SDOH across diagnoses. Individual-level SDOH factors (age, marital status, and race) were strongly associated with eLLST, predicting eLLST more strongly than admission severity. Individual-level SDOH were more strongly predictive of eLLST than neighborhood-level SDOH. CONCLUSIONS: Across diagnoses, eLLST varied by home geography and was predicted by individual-level SDOH and neighborhood-level SDOH more so than by admission severity. Structured shared decision-making tools may therefore represent tools for health equity. Additionally, these findings provide a major warning: prognostic and artificial intelligence models seeking to predict outcomes such as mortality or emergence from disorders of consciousness may be encoded with self-fulfilling biases of geography and demographics.

Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry.

AIMS: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. METHODS AND RESULTS: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. CONCLUSION: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator.

The association between age at breast cancer diagnosis and prevalence of pathogenic variants.

PURPOSE: Young age at breast cancer (BC) diagnosis and family history of BC are strongly associated with high prevalence of pathogenic variants (PVs) in BRCA1 and BRCA2 genes. There is limited evidence for such associations with moderate/high penetrance BC-risk genes such as ATM, CHEK2, and PALB2. METHODS: We analyzed multi-gene panel testing results (09/2013-12/2019) for women unaffected by any cancer (N = 371,594) and those affected with BC (N = 130,151) ascertained for suspicion of hereditary breast and/or ovarian cancer. Multivariable logistic regression was used to test association between PV status and age at BC diagnosis (≤ 45 vs. > 45 years) or family history of BC after controlling for personal/family non-BC histories and self-reported ancestry. RESULTS: An association between young age (≤ 45 years) at diagnosis and presence of PVs was strong for BRCA1 (OR 3.95, 95% CI 3.64-4.29) and moderate for BRCA2 (OR 1.98, 95% CI 1.84-2.14). Modest associations were observed between PVs and young age at diagnosis for ATM (OR 1.22, 95% CI 1.08-1.37) and CHEK2 (OR 1.34, 95% CI 1.21-1.47) genes, but not for PALB2 (OR 1.12, 95% CI 0.98-1.27). For women with BC, earliest age of familial BC diagnosis followed a similar pattern. For unaffected women, earliest age of family cancer diagnosis was significantly associated with PV status only for BRCA1 (OR 2.34, 95% CI 2.13-2.56) and BRCA2 (OR 1.25, 95% CI 1.16-1.35). CONCLUSIONS: Young age at BC diagnosis is not a strong risk factor for carrying PVs in BC-associated genes ATM, CHEK2, or PALB2.

Practice Standards for the Use of Multimodality Neuromonitoring: A Delphi Consensus Process.

OBJECTIVES: To address areas in which there is no consensus for the technologies, effort, and training necessary to integrate and interpret information from multimodality neuromonitoring (MNM). DESIGN: A three-round Delphi consensus process. SETTING: Electronic surveys and virtual meeting. SUBJECTS: Participants with broad MNM expertise from adult and pediatric intensive care backgrounds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two rounds of surveys were completed followed by a virtual meeting to resolve areas without consensus and a final survey to conclude the Delphi process. With 35 participants consensus was achieved on 49% statements concerning MNM. Neurologic impairment and the potential for MNM to guide management were important clinical considerations. Experts reached consensus for the use of MNM-both invasive and noninvasive-for patients in coma with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial hemorrhage. There was consensus that effort to integrate and interpret MNM requires time independent of daily clinical duties, along with specific skills and expertise. Consensus was reached that training and educational platforms are necessary to develop this expertise and to provide clinical correlation. CONCLUSIONS: We provide expert consensus in the clinical considerations, minimum necessary technologies, implementation, and training/education to provide practice standards for the use of MNM to individualize clinical care.

Transcatheter versus surgical treatment for isolated superior sinus venosus atrial septal defect.

BACKGROUND: The superior sinus venosus atrial septal defect is a congenital communication between the left and right atria. Open surgical approach by patch closure has historically been the only treatment option. Recently, a transcatheter approach has been developed. This study aims to compare the efficacy and safety of surgical and transcatheter approach in treatment of sinus venosus atrial septal defect. METHODS: Between March 2010 and December 2020, 58 patients (median age: 45.4, range 14.8-73.8) underwent either surgical or transcatheter correction of superior sinus venosus atrial septal defect with partial anomalous pulmonary venous drainage. RESULTS: Twenty-four patients (median age: 35.4, range 14.8-66.8) underwent surgery while 34 patients (median age: 46.8, range 15.5-73.8) had a transcatheter treatment. During the catheterization era, 41 patients was considered suitable for a transcatheter closure. In 5 patients, surgery was the patient's or referring physician's choice. In 2 cases, the procedure was unsuccessful; the remaining 34 were successfully closed (94.4% of cases). Intensive care unit stay (median of 1 day, range 0.5-4, vs. 0, range 0-2, p < 0.0001) and hospital stay (median 7 days, range 2-15 vs. 2 days, range 1-12, p < 0.0001), were significantly longer in the surgery group. Total early complication rate, consisted on procedural and in-hospital complication, were higher in the surgical group (62.5% vs. 23.5%; p = 0.005). However, complications in both groups were clinically mild. At follow-up, a small residual shunt was present in 6 patients (surgery group: 2 pts; catheterization group: 4 pts; p: NS). Imaging studies showed significant improvement of right ventricular size and unobstructed pulmonary venous return in all patients. No late complications occurred at follow-up. CONCLUSIONS: Transcatheter correction of sinus venosus atrial septal defect is effective and safe in selected patients and may be considered as a valid alternative to surgery.

Sinus node dysfunction during transcatheter assessment and stent correction of sinus venosus atrial septal defects.

Covered stent correction of a superior sinus venosus atrial septal defect is increasingly performed as an alternative to surgical repair. While sinus node dysfunction requiring pacemaker implantation may be required after surgical repair, this has not been previously reported after covered stent implantation. We reviewed the experience in two interventional centers. Balloon inflation in the superior vena cava was used to confirm the anomalous pulmonary vein drainage would be unobstructed after stent implantation. During balloon testing in 62 consecutive patients, we assessed gradients across the pulmonary vein to left atrium while monitoring the rhythm. We observed the outcomes after covered stent correction in 51 patients. In a single patient, significant bradycardia and pauses developed on repeat balloon testing and the procedure was abandoned without stent implantation. In another patient, there was no sign of sinus node dysfunction during balloon testing but several hours after stent implantation, the patient became symptomatic from sinus bradycardia and pauses and had a pacemaker implanted 3 days later. Over a year later there are some signs of improvement in sinus node function. While sinus node dysfunction has not been described previously during balloon testing or after stent implantation, this report demonstrates for the first time that it may occur. Larger registries are therefore required to monitor for this uncommon complication.

Ethical Considerations in Neuroprognostication Following Acute Brain Injury.

Neuroprognostication following acute brain injury (ABI) is a complex process that involves integrating vast amounts of information to predict a patient's likely trajectory of neurologic recovery. In this setting, critically evaluating salient ethical questions is imperative, and the implications often inform high-stakes conversations about the continuation, limitation, or withdrawal of life-sustaining therapy. While neuroprognostication is central to these clinical "life-or-death" decisions, the ethical underpinnings of neuroprognostication itself have been underexplored for patients with ABI. In this article, we discuss the ethical challenges of individualized neuroprognostication including parsing and communicating its inherent uncertainty to surrogate decision-makers. We also explore the population-based ethical considerations that arise in the context of heterogenous prognostication practices. Finally, we examine the emergence of artificial intelligence-aided neuroprognostication, proposing an ethical framework relevant to both modern and longstanding prognostic tools.

Why ketamine.

We present the rationale for testing ketamine as an add-on therapy for treating benzodiazepine refractory (established) status epilepticus. In animal studies, ketamine terminates benzodiazepine refractory status epilepticus by interfering with the pathophysiological mechanisms and is a neuroprotectant. Ketamine does not suppress respiration when used for sedation and anesthesia. A Series of reports suggest that ketamine can help terminate refractory and super refractory status epilepticus. We propose to use 1 or 3 mg/Kg ketamine intravenously based on animal-to-human conversion and pharmacokinetic studies. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Practice-Pattern Variation in Sedation of Neurotrauma Patients in the Intensive Care Unit: An International Survey.

Background: Analgo-sedation plays an important role during intensive care management of traumatic brain injury (TBI) patients, however, limited evidence is available to guide practice. We sought to quantify practice-pattern variation in neurotrauma sedation management, surveying an international sample of providers. Methods: An electronic survey consisting of 56 questions was distributed internationally to neurocritical care providers utilizing the Research Electronic Data Capture platform. Descriptive statistics were used to quantitatively describe and summarize the responses. Results: Ninety-five providers from 37 countries responded. 56.8% were attending physicians with primary medical training most commonly in intensive care medicine (68.4%) and anesthesiology (26.3%). Institutional sedation guidelines for TBI patients were available in 43.2%. Most common sedative agents for induction and maintenance, respectively, were propofol (87.5% and 88.4%), opioids (60.2% and 70.5%), and benzodiazepines (53.4% and 68.4%). Induction and maintenance sedatives, respectively, are mostly chosen according to provider preference (68.2% and 58.9%) rather than institutional guidelines (26.1% and 35.8%). Sedation duration for patients with intracranial hypertension ranged from 24 h to 14 days. Neurological wake-up testing (NWT) was routinely performed in 70.5%. The most common NWT frequency was every 24 h (47.8%), although 20.8% performed NWT at least every 2 h. Richmond Agitation and Sedation Scale targets varied from deep sedation (34.7%) to alert and calm (17.9%). Conclusions: Among critically ill TBI patients, sedation management follows provider preference rather than institutional sedation guidelines. Wide practice-pattern variation exists for the type, duration, and target of sedative management and NWT performance. Future comparative effectiveness research investigating these differences may help optimize sedation strategies to promote recovery.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Physiology and Big Data.

BACKGROUND: The implementation of multimodality monitoring in the clinical management of patients with disorders of consciousness (DoC) results in physiological measurements that can be collected in a continuous and regular fashion or even at waveform resolution. Such data are considered part of the "Big Data" available in intensive care units and are potentially suitable for health care-focused artificial intelligence research. Despite the richness in content of the physiological measurements, and the clinical implications shown by derived metrics based on those measurements, they have been largely neglected from previous attempts in harmonizing data collection and standardizing reporting of results as part of common data elements (CDEs) efforts. CDEs aim to provide a framework for unifying data in clinical research and help in implementing a systematic approach that can facilitate reliable comparison of results from clinical studies in DoC as well in international research collaborations. METHODS: To address this need, the Neurocritical Care Society's Curing Coma Campaign convened a multidisciplinary panel of DoC "Physiology and Big Data" experts to propose CDEs for data collection and reporting in this field. RESULTS: We report the recommendations of this CDE development panel and disseminate CDEs to be used in physiologic and big data studies of patients with DoC. CONCLUSIONS: These CDEs will support progress in the field of DoC physiologic and big data and facilitate international collaboration.

Automated Annotation of Epileptiform Burden and Its Association with Outcomes.

OBJECTIVE: This study was undertaken to determine the dose-response relation between epileptiform activity burden and outcomes in acutely ill patients. METHODS: A single center retrospective analysis was made of 1,967 neurologic, medical, and surgical patients who underwent >16 hours of continuous electroencephalography (EEG) between 2011 and 2017. We developed an artificial intelligence algorithm to annotate 11.02 terabytes of EEG and quantify epileptiform activity burden within 72 hours of recording. We evaluated burden (1) in the first 24 hours of recording, (2) in the 12-hours epoch with highest burden (peak burden), and (3) cumulatively through the first 72 hours of monitoring. Machine learning was applied to estimate the effect of epileptiform burden on outcome. Outcome measure was discharge modified Rankin Scale, dichotomized as good (0-4) versus poor (5-6). RESULTS: Peak epileptiform burden was independently associated with poor outcomes (p < 0.0001). Other independent associations included age, Acute Physiology and Chronic Health Evaluation II score, seizure on presentation, and diagnosis of hypoxic-ischemic encephalopathy. Model calibration error was calculated across 3 strata based on the time interval between last EEG measurement (up to 72 hours of monitoring) and discharge: (1) <5 days between last measurement and discharge, 0.0941 (95% confidence interval [CI] = 0.0706-0.1191); 5 to 10 days between last measurement and discharge, 0.0946 (95% CI = 0.0631-0.1290); >10 days between last measurement and discharge, 0.0998 (95% CI = 0.0698-0.1335). After adjusting for covariates, increase in peak epileptiform activity burden from 0 to 100% increased the probability of poor outcome by 35%. INTERPRETATION: Automated measurement of peak epileptiform activity burden affords a convenient, consistent, and quantifiable target for future multicenter randomized trials investigating whether suppressing epileptiform activity improves outcomes. ANN NEUROL 2021;90:300-311.

Cohort study of congenital complete heart block among preterm neonates: a single-center experience over a 15-year period.

Congenital complete heart block (CCHB) is a very rare condition, with high risk of mortality. Prematurity is associated with immaturity of the cardiovascular system. Morbidity related to CCHB and prematurity has never been described. We describe a tertiary perinatal center experience over a 15-year period on CCHB management and complications in preterm infants. This is a single-center observational cohort study. All neonates admitted to neonatal intensive care unit with a diagnosis of isolated CCHB between January 2006 and January 2021 were identified. All preterm neonates (< 37 weeks) were compared with a control cohort of term neonates (≥ 37 weeks). Antenatal data, complications of prematurity, medical, and surgical management of CCHB were recorded. Twenty-four neonates with isolated CCHB (16 preterm and 8 term) were born during the study period, including 5 very preterm (< 32 weeks) and 11 preterm (32 to 37 weeks). All very preterm were born via emergency caesarian section without antenatal steroid administration. They had multiple severe morbidities including chronic lung disease, necrotizing enterocolitis, grades 3-4 intraventricular hemorrhage, cystic periventricular leukomalacia, and longer periods of mechanical and non-invasive ventilatory support than preterm. Thirteen out of sixteen preterm infants had permanent pacemakers inserted, compared to 1/8 for term newborns. All babies born before 35-week gestation were either paced or died.Conclusion: Premature neonates with CCHB have high risk of mortality and morbidity especially if undiagnosed and born by unnecessary emergency caesarian section without antenatal steroids. Prematurity below 35 weeks may be associated with death or pacemaker insertion. This supports better antenatal screening to avoid induced prematurity. What is Known: • Congenital complete heart block is a very rare condition associated with high morbidity and mortality. • Antenatal risk factors for poor outcome include fetal hydrops, low ventricular rate (HR <55 beats per minute), and congenital heart defect. What is New: • Infants born <32 weeks with CCHB had no antenatal steroid administration, and sustained high burden of morbidity (chronic lung disease, intraventricular hemorrhage, and cystic periventricular leukomalacia). • Birth <35 weeks is strongly associated with requiring pacing prior to discharge or death.

Anti-seizure medication treatment and outcomes in acute ischemic stroke patients undergoing continuous EEG monitoring.

OBJECTIVES: To determine the association of anti-seizure medication (ASM) treatment with outcomes in acute ischemic stroke (AIS) patients undergoing continuous electroencephalography (cEEG). METHODS: Retrospective analysis of AIS patients admitted between 2012 and 2019. The following are the inclusion criteria: age ≥ 18 years and ≥ 16 h of cEEG within the first 7 days of admission. ASM treatment exposure was defined as > 48 h of treatment after the first 24 h of cEEG. The primary outcome measure was 90-day mortality, and the secondary outcome was 90-day functional recovery (Modified Ranking Scale 0-3). Propensity scores were used to adjust for baseline covariates and presence of epileptiform abnormalities (seizures, periodic and rhythmic patterns). RESULTS: One hundred thirteen patients met the inclusion criteria; 39 (34.5%) were exposed to ASM. ASM treatment was not associated with 90-day mortality (propensity adjusted HR 1.0 [0.31-3.27], p = 0.999) or functional outcomes (adjusted HR 0.99 [0.32-3.02], p = 0.989), compared to no treatment. CONCLUSIONS: In our study, ASM treatment in AIS patients with cEEG abnormalities was not significantly associated with a change in 90-day mortality and functional recovery. Larger comparative effectiveness studies are indicated to identify which acute ischemic stroke patients with cEEG abnormalities benefit most from ASM treatment.

Harmonization of Physiological Data in Neurocritical Care: Challenges and a Path Forward.

Continuous multimodal monitoring in neurocritical care provides valuable insights into the dynamics of the injured brain. Unfortunately, the "readiness" of this data for robust artificial intelligence (AI) and machine learning (ML) applications is low and presents a significant barrier for advancement. Harmonization standards and tools to implement those standards are key to overcoming existing barriers. Consensus in our professional community is essential for success.

Cortical Spreading Depolarizations and Clinically Measured Scalp EEG Activity After Aneurysmal Subarachnoid Hemorrhage and Traumatic Brain Injury.

BACKGROUND: Spreading depolarizations (SDs) are associated with worse outcome following subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but gold standard detection requires electrocorticography with a subdural strip electrode. Electroencephalography (EEG) ictal-interictal continuum abnormalities are associated with poor outcomes after TBI and with both delayed cerebral ischemia (DCI) and poor outcomes after SAH. We examined rates of SD detection in patients with SAH and TBI with intraparenchymal and subdural strip electrodes and assessed which continuous EEG (cEEG) measures were associated with intracranially quantified SDs. METHODS: In this single-center cohort, we included patients with SAH and TBI undergoing ≥ 24 h of interpretable intracranial monitoring via eight-contact intraparenchymal or six-contact subdural strip platinum electrodes or both. SDs were rated according to established consensus criteria and compared with cEEG findings rated according to the American Clinical Neurophysiology Society critical care EEG monitoring consensus criteria: lateralized rhythmic delta activity, generalized rhythmic delta activity, lateralized periodic discharges, generalized periodic discharges, any ictal-interictal continuum, or a composite scalp EEG tool for seizure risk estimation: the 2HELPS2B score. Among patients with SAH, cEEG was assessed for validated DCI biomarkers: new or worsening epileptiform abnormalities and new background deterioration. RESULTS: Over 6 years, SDs were recorded in 5 (18%) of 28 patients recorded with intraparenchymal electrodes and 4 (40%) of 10 patients recorded with subdural strip electrodes. There was no significant association between occurrence of SDs and day 1 cEEG findings (American Clinical Neurophysiology Society main terms lateralized periodic discharges, generalized periodic discharges, lateralized rhythmic delta activity, or seizures, individually or in combination). After SAH, established cEEG DCI predictors were not associated with SDs. CONCLUSIONS: Intraparenchymal recordings yielded low rates of SD, and documented SDs were not associated with ictal-interictal continuum abnormalities or other cEEG DCI predictors. Identifying scalp EEG correlates of SD may require training computational EEG analytics and use of gold standard subdural strip electrocorticography recordings.

Neurocritical Care Performance Measures Derived from Electronic Health Record Data are Feasible and Reveal Site-Specific Variation: A CHoRUS Pilot Project.

BACKGROUND: We evaluated the feasibility and discriminability of recently proposed Clinical Performance Measures for Neurocritical Care (Neurocritical Care Society) and Quality Indicators for Traumatic Brain Injury (Collaborative European NeuroTrauma Effectiveness Research in TBI; CENTER-TBI) extracted from electronic health record (EHR) flowsheet data. METHODS: At three centers within the Collaborative Hospital Repository Uniting Standards (CHoRUS) for Equitable AI consortium, we examined consecutive neurocritical care admissions exceeding 24 h (03/2015-02/2020) and evaluated the feasibility, discriminability, and site-specific variation of five clinical performance measures and quality indicators: (1) intracranial pressure (ICP) monitoring (ICPM) within 24 h when indicated, (2) ICPM latency when initiated within 24 h, (3) frequency of nurse-documented neurologic assessments, (4) intermittent pneumatic compression device (IPCd) initiation within 24 h, and (5) latency to IPCd application. We additionally explored associations between delayed IPCd initiation and codes for venous thromboembolism documented using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) system. Median (interquartile range) statistics are reported. Kruskal-Wallis tests were measured for differences across centers, and Dunn statistics were reported for between-center differences. RESULTS: A total of 14,985 admissions met inclusion criteria. ICPM was documented in 1514 (10.1%), neurologic assessments in 14,635 (91.1%), and IPCd application in 14,175 (88.5%). ICPM began within 24 h for 1267 (83.7%), with site-specific latency differences among sites 1-3, respectively, (0.54 h [2.82], 0.58 h [1.68], and 2.36 h [4.60]; p < 0.001). The frequency of nurse-documented neurologic assessments also varied by site (17.4 per day [5.97], 8.4 per day [3.12], and 15.3 per day [8.34]; p < 0.001) and diurnally (6.90 per day during daytime hours vs. 5.67 per day at night, p < 0.001). IPCds were applied within 24 h for 12,863 (90.7%) patients meeting clinical eligibility (excluding those with EHR documentation of limiting injuries, actively documented as ambulating, or refusing prophylaxis). In-hospital venous thromboembolism varied by site (1.23%, 1.55%, and 5.18%; p < 0.001) and was associated with increased IPCd latency (overall, 1.02 h [10.4] vs. 0.97 h [5.98], p = 0.479; site 1, 2.25 h [10.27] vs. 1.82 h [7.39], p = 0.713; site 2, 1.38 h [5.90] vs. 0.80 h [0.53], p = 0.216; site 3, 0.40 h [16.3] vs. 0.35 h [11.5], p = 0.036). CONCLUSIONS: Electronic health record-derived reporting of neurocritical care performance measures is feasible and demonstrates site-specific variation. Future efforts should examine whether performance or documentation drives these measures, what outcomes are associated with performance, and whether EHR-derived measures of performance measures and quality indicators are modifiable.

Antiseizure Medication Treatment and Outcomes in Patients with Subarachnoid Hemorrhage Undergoing Continuous EEG Monitoring.

BACKGROUND: Patients with aneurysmal subarachnoid hemorrhage (aSAH) with electroencephalographic epileptiform activity (seizures, periodic and rhythmic patterns, and sporadic discharges) are frequently treated with antiseizure medications (ASMs). However, the safety and effectiveness of ASM treatment for epileptiform activity has not been established. We used observational data to investigate the effectiveness of ASM treatment in patients with aSAH undergoing continuous electroencephalography (cEEG) to develop a causal hypothesis for testing in prospective trials. METHODS: This was a retrospective single-center cohort study of patients with aSAH admitted between 2011 and 2016. Patients underwent ≥ 24 h of cEEG within 4 days of admission. All patients received primary ASM prophylaxis until aneurysm treatment (typically within 24 h of admission). Treatment exposure was defined as reinitiation of ASMs after aneurysm treatment and cEEG initiation. We excluded patients with non-cEEG indications for ASMs (e.g., epilepsy, acute symptomatic seizures). Outcomes measures were 90-day mortality and good functional outcome (modified Rankin Scale scores 0-3). Propensity scores were used to adjust for baseline covariates and disease severity. RESULTS: Ninety-four patients were eligible (40 continued ASM treatment; 54 received prophylaxis only). ASM continuation was not significantly associated with higher 90-day mortality (propensity-adjusted hazard ratio [HR] = 2.01 [95% confidence interval (CI) 0.57-7.02]). ASM continuation was associated with lower likelihood for 90-day good functional outcome (propensity-adjusted HR = 0.39 [95% CI 0.18-0.81]). In a secondary analysis, low-intensity treatment (low-dose single ASM) was not significantly associated with mortality (propensity-adjusted HR = 0.60 [95% CI 0.10-3.59]), although it was associated with a lower likelihood of good outcome (propensity-adjusted HR = 0.37 [95% CI 0.15-0.91]), compared with prophylaxis. High-intensity treatment (high-dose single ASM, multiple ASMs, or anesthetics) was associated with higher mortality (propensity-adjusted HR = 6.80 [95% CI 1.67-27.65]) and lower likelihood for good outcomes (propensity-adjusted HR = 0.30 [95% CI 0.10-0.94]) compared with prophylaxis only. CONCLUSIONS: Our findings suggest the testable hypothesis that continuing ASMs in patients with aSAH with cEEG abnormalities does not improve functional outcomes. This hypothesis should be tested in prospective randomized studies.

Prognostication in Acute Neurological Emergencies.

BACKGROUND: For patients with acute, serious neurological conditions presenting to the emergency department (ED), prognostication is typically based on clinical experience, scoring systems and patient co-morbidities. Because estimating a poor prognosis influences caregiver decisions to withdraw life-sustaining therapy, we investigated the consistency of prognostication across a spectrum of neurology physicians. METHODS: Five acute neurological presentations (2 with large hemispheric infarction; 1 with brainstem infarction, 1 with lobar hemorrhage, and 1 with hypoxic-ischemic encephalopathy) were selected for a department-wide prognostication simulation exercise. All had presented to our tertiary care hospital's ED, where a poor outcome was predicted by the ED neurology team within 24 hours of onset. Relevant clinical, laboratory and imaging data available before ED prognostication were presented on a web-based platform to 120 providers blinded to the actual outcome. The provider was requested to rank-order, from most to least likely, the predicted 90-day modified Rankin Scale (mRS) score. To determine the accuracy of individual outcome predictions we compared the patient's the actual 90-day mRS score to highest ranked predicted mRS score. Additionally, the group's "weighted" outcomes, accounting for the entire spectrum of mRS scores ranked by all respondents, were compared to the actual outcome for each case. Consistency was compared between pre-specified provider roles: neurology trainees versus faculty; non-vascular versus vascular faculty. RESULTS: Responses ranged from 106-110 per case. Individual predictions were highly variable, with predictions matching the actual mRS scores in as low as 2% of respondents in one case and 95% in another case. However, as a group, the weighted outcome matched the actual mRS score in 3 of 5 cases (60%). There was no significant difference between subgroups based on expertise (stroke/neurocritical care versus other) or experience (faculty versus trainee) in 4 of 5 cases. CONCLUSION: Acute neuro-prognostication is highly variable and often inaccurate among neurology providers. Significant differences are not attributable to experience or subspecialty expertise. The mean outcome prediction from group of providers ("the wisdom of the crowd") may be superior to that of individual providers.

Early Brain Injury and Soluble ST2 After Nontraumatic Subarachnoid Hemorrhage.

[Figure: see text].