Objective This study was undertaken to describe patterns of benzodiazepine use as first‐line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second‐line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). Methods Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second‐line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline‐recommended dosing. Logistic regression was used to determine the association of the first dose of benzodiazepine and the cumulative benzodiazepine dose with the response to second‐line agent. Results Four hundred sixty patients were administered 1170 doses of benzodiazepines (669 lorazepam, 398 midazolam, 103 diazepam). Lorazepam was most frequently administered intravenously in the emergency department, midazolam intramuscularly or intravenously by the emergency medical services personnel, and diazepam rectally prior to ambulance arrival. The first dose of the first benzodiazepine (N = 460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, >85% of midazolam and >76% of lorazepam administrations were lower than recommended. Higher first or cumulative benzodiazepine doses were not associated with better outcomes or clinical seizure cessation in response to second‐line medications in these benzodiazepine‐refractory seizures. Significance Benzodiazepines as first‐line treatment of SE, particularly midazolam and lorazepam, are frequently underdosed throughout the United States. This broad and generalizable cohort confirms prior single site reports that underdosing is both pervasive and difficult to remediate. (ESETT ClinicalTrials.gov identifier: NCT01960075.)
Objective: To evaluate recovery from neuromuscular blockade in infants using Train-of-Four nerve stimulation. Study Design: Ulnar nerve stimulation was used to evoke thumb twitch and reported as Train-of-Four ratio. Thumb twitch was also recorded visually in real-time. Primary outcome was time to near recovery of muscle function (Train-of-Four ratio >70%). Secondary analyses were time to greater degrees of recovery (Train-of-Four ratio >80, 90%), sensitivity of accelerometry vs. visual thumb-twitch and clinical variates to assess safety. Results: Patients were enrolled following rocuronium-boluses (n = 10) and vecuronium-infusions (n = 9). Median recovery time to Train-of-Four ratio >70% was 14 h following rocuronium-bolus dosing and 34 h following cessation of continuous vecuronium infusion. Median stimulus threshold for accelerometry was 27.5 mA and visual observation was 20 mA. There were no safety concerns. Conclusion(s): Neuromuscular monitoring using Train-of-Four nerve stimulation is feasible in infants. Some infants exhibited prolonged recovery from neuromuscular-blockade. These pilot data may facilitate future standardized pediatric protocols on neuromuscular monitoring for safer dosing.
ImportanceLow-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in patients undergoing LDCT lung screening. However, the exact nature of these SIF findings has not been described.ObjectiveTo describe SIFs reported in the LDCT arm of the National Lung Screening Trial and classify SIFs as reportable or not reportable to the referring clinician (RC) using the American College of Radiology’s white papers on incidental findings.Design, Setting, and ParticipantsThis was a retrospective case series study of 26 455 participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT. The trial was conducted from 2002 to 2009, and data were collected at 33 US academic medical centers.Main Outcomes and MeasuresSignificant incident findings were defined as a final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer or a positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm.ResultsOf 26 455 participants, 10 833 (41.0%) were women, the mean (SD) age was 61.4 (5.0) years, and there were 1179 (4.5%) Black, 470 (1.8%) Hispanic/Latino, and 24 123 (91.2%) White individuals. Participants were scheduled to undergo 3 screenings during the course of the trial; the present study included 75 126 LDCT screening examinations performed for 26 455 participants. A SIF was reported for 8954 (33.8%) of 26 455 participants who were screened with LDCT. Of screening tests with a SIF detected, 12 228 (89.1%) had a SIF considered reportable to the RC, with a higher proportion of reportable SIFs among those with a positive screen result for lung cancer (7632 [94.1%]) compared with those with a negative screen result (4596 [81.8%]). The most common SIFs reported included emphysema (8677 [43.0%] of 20 156 SIFs reported), coronary artery calcium (2432 [12.1%]), and masses or suspicious lesions (1493 [7.4%]). Masses included kidney (647 [3.2%]), liver (420 [2.1%]), adrenal (265 [1.3%]), and breast (161 [0.8%]) abnormalities. Classification was based on free-text comments; 2205 of 13 299 comments (16.6%) could not be classified. The hierarchical reporting of final diagnosis in NLST may have been associated with an overestimate of severe emphysema in participants with a positive screen result for lung cancer.Conclusions and RelevanceThis case series study found that SIFs were commonly reported in the LDCT arm of the National Lung Screening Trial, and most of these SIFs were considered reportable to the RC and likely to require follow-up. Future screening trials should standardize SIF reporting.
It is unknown how often and how early EEG is obtained in patients presenting with status epilepticus. The Established Status Epilepticus Treatment Trial enrolled patients with benzodiazepinerefractory seizures and randomized participants to fosphenytoin, levetiracetam, or valproate. The use of early EEG, including frequency of electrographic seizures, was determined in Established Status Epilepticus Treatment Trial participants.Methods: Secondary analysis of 475 enrollments at 58 hospitals to determine the frequency of EEG performed within 24 hours of presentation. The EEG type, the prevalence of electrographic seizures, and characteristics associated with obtaining early EEG were recorded. Chi-square and Wilcoxon rank-sum tests were calculated as appropriate for univariate and bivariate comparisons. Odds ratios are reported with 95% confidence intervals.Results: A total of 278 of 475 patients (58%) in the Established Status Epilepticus Treatment Trial cohort underwent EEG within 24 hours (median time to EEG: 5 hours [interquartile range: 3-10]). Electrographic seizure prevalence was 14% (95% confidence interval, 10%-19%; 39/278) in the entire cohort and 13% (95% confidence interval, 7%-21%) in the subgroup of patients meeting the primary outcome of the Established Status Epilepticus Treatment Trial (clinical treatment success within 60 minutes of randomization). Among subjects diagnosed with electrographic seizures (39), 15 (38%; 95% confidence interval, 25%-54%) had no clinical correlate on the video EEG recording.Conclusions: Electrographic seizures may occur in patients who stop seizing clinically after treatment of convulsive status epilepticus. Clinical correlates might not be present during electrographic seizures. These findings support early initiation of EEG recordings in patients suffering from convulsive status epilepticus, including those with clinical evidence of treatment success.
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