Comparing Intubation Rates in Patients Receiving Parenteral Olanzapine With and Without a Parenteral Benzodiazepine in the Emergency Department.

STUDY OBJECTIVE: United States prescribing information recommends against coadministration of injectable olanzapine with injectable benzodiazepines due to a risk of cardiorespiratory depression, whereas European prescribing information recommends the 2 drugs not be administered within 60 minutes of each other. In contrast, a recently published American College of Emergency Physicians clinical policy recommends injectable olanzapine and benzodiazepines be coadministered for treating severe agitation. We sought to compare injectable olanzapine with and without injectable benzodiazepines for evidence of cardiorespiratory depression. METHODS: We performed a retrospective study of patients in an urban emergency department from January 2017 through November 2019 who received parenteral olanzapine with or without parenteral benzodiazepines. We included patients receiving 2 total medication doses, either olanzapine+benzodiazepine or 2 doses of olanzapine, coadministered within 60 minutes. The primary outcome was tracheal intubation in the emergency department. Secondary outcomes included hypotension (systolic blood pressure less than 90 mmHg) and hypoxemia (SpO2 less than 90%). RESULTS: We identified 693 patients (median [alcohol]=210 mg/dL, median age=37 years [IQR 29 to 49]). In total, 549 received 2 doses of olanzapine, and 144 patients received olanzapine and a benzodiazepine. We found no difference in intubation rates between the olanzapine-only group (21/549, 3.8%) and the olanzapine+benzodiazepine group (5/144, 3.5%; difference=0.3%, 95% confidence interval -3.0% to 3.7%). Rates of hypoxemia (2% olanzapine-only and 3% olanzapine+benzodiazepine) and hypotension (9% both groups) also were not different between groups. CONCLUSION: We found no difference in cardiorespiratory depression between patients receiving only olanzapine versus olanzapine plus a benzodiazepine.

Use of large language models to optimize poison center charting.

INTRODUCTION: Efficient and complete medical charting is essential for patient care and research purposes. In this study, we sought to determine if Chat Generative Pre-Trained Transformer could generate cogent, suitable charts from recorded, real-world poison center calls and abstract and tabulate data. METHODS: De-identified transcripts of real-world hospital-initiated poison center consults were summarized by Chat Generative Pre-Trained Transformer 4.0. Additionally, Chat Generative Pre-Trained Transformer organized tables for data points, including vital signs, test results, therapies, and recommendations. Seven trained reviewers, including certified specialists in poison information and board-certified medical toxicologists, graded summaries using a 1 to 5 scale to determine appropriateness for entry into the medical record. Intra-rater reliability was calculated. Tabulated data was quantitatively evaluated for accuracy. Finally, reviewers selected preferred documentation: original or Chat Generative Pre-Trained Transformer organized. RESULTS: Eighty percent of summaries had a median score high enough to be deemed appropriate for entry into the medical record. In three duplicate cases, reviewers did change scores, leading to moderate intra-rater reliability (kappa = 0.6). Among all cases, 91 percent of data points were correctly abstracted into table format. DISCUSSION: By utilizing a large language model with a unified prompt, charts can be generated directly from conversations in seconds without the need for additional training. Charts generated by Chat Generative Pre-Trained Transformer were preferred over extant charts, even when they were deemed unacceptable for entry into the medical record prior to the correction of errors. However, there were several limitations to our study, including poor intra-rater-reliability and a limited number of cases examined. CONCLUSIONS: In this study, we demonstrate that large language models can generate coherent summaries of real-world poison center calls that are often acceptable for entry to the medical record as is. When errors were present, these were often fixed with the addition or deletion of a word or phrase, presenting an enormous opportunity for efficiency gains. Our future work will focus on implementing this process in a prospective fashion.

Massive Sodium Nitrite Overdose: A Case for Prehospital Methylene Blue.

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

Fomepizole Therapy for Acetaminophen-Induced Liver Failure in an Infant.

Acetaminophen overdose is common in the pediatric population. N-acetylcysteine (NAC) is effective at preventing liver injury in most patients when started shortly after the overdose. Delays to therapy increase risk of hepatotoxicity and liver failure that may necessitate organ transplant. Animal studies have demonstrated fomepizole may provide added benefit in acetaminophen overdose because of its ability to block the metabolic pathway that produces the toxic acetaminophen metabolite and downstream inhibition of oxidative stress pathways that lead to cell death. Several adult case reports describe use of fomepizole in patients at higher risk for poor outcomes despite NAC. We describe a case of a 7-month-old female who presented in acute liver failure with persistently elevated acetaminophen concentration secondary to repeated supratherapeutic doses of acetaminophen to manage fever. Fomepizole and NAC antidotes were used in the management of the patient. She fully recovered despite demonstrating multiple markers of poor outcome on initial presentation. Although randomized trials are lacking, this case suggests that fomepizole may safely provide additional benefit in pediatric patients at risk for severe acetaminophen toxicity.

Toxic Tetrahydrocannabinol (THC) Dose in Pediatric Cannabis Edible Ingestions.

OBJECTIVE: The study characterizes cannabis toxicity in relation to tetrahydrocannabinol (THC) dose in pediatric edible cannabis ingestions. METHODS: This is a retrospective review of children aged <6 years presenting with edible cannabis ingestions of known THC dose within a pediatric hospital network (January 1, 2015-October 25, 2022). Cannabis toxicity was characterized as severe if patients exhibited severe cardiovascular (bradycardia, tachycardia/hypotension requiring vasopressors or intravenous fluids, other dysrhythmias), respiratory (respiratory failure, apnea, requiring oxygen supplementation), or neurologic (seizure, myoclonus, unresponsiveness, responsiveness to painful stimulation only, requiring intubation or sedation) effects. Cannabis toxicity was characterized as prolonged if patients required >6 hours to reach baseline. The relationship between THC dose and severe and prolonged toxicity was explored using multivariable logistic regression and receiver operator characteristic curve analyses. RESULTS: Eighty patients met inclusion. The median age was 2.9 years. The median THC ingestion was 2.1 mg/kg. Severe and prolonged toxicity was present in 46% and 74%, respectively. THC dose was a significant predictor of severe (adjusted odds ratio 2.9, 95% confidence interval: 1.8-4.7) and prolonged toxicity (adjusted odds ratio 3.2, 95% confidence interval: 1.6-6.5), whereas age and sex were not. Area under the curve was 92.9% for severe and 87.3% for prolonged toxicity. THC ingestions of ≥1.7 mg/kg can predict severe (sensitivity 97.3%) and prolonged toxicity (sensitivity 75.4%). CONCLUSIONS: The THC dose of edible cannabis correlates to the degree of toxicity in children <6 years old. The threshold of 1.7 mg/kg of THC may guide medical management and preventive regulations.

Feasibility of detecting snake envenomation biomarkers from dried blood spots.

Biofluid proteomics is a sensitive and high throughput technique that provides vast amounts of molecular data for biomarker discovery. More recently, dried blood spots (DBS) have gained traction as a stable, noninvasive, and relatively cheap source of proteomic data for biomarker identification in disease and injury. Snake envenomation is responsible for significant morbidity and mortality worldwide; however, much remains unknown about the systemic molecular response to envenomation and acquiring biological samples for analysis is a major hurdle. In this study, we utilized DBS acquired from a case of lethal rattlesnake envenomation to determine the feasibility of discovering biomarkers associated with human envenomation. We identified proteins that were either unique or upregulated in envenomated blood compared to non-envenomated blood and evaluated if physiological response pathways and protein markers that correspond to the observed syndromes triggered by envenomation could be detected. We demonstrate that DBS provide useful proteomic information on the systemic processes that resulted from envenomation in this case and find evidence for a massive and systemic inflammatory cascade, combined with coagulation dysregulation, complement system activation, hypoxia response activation, and apoptosis. We also detected potential markers indicative of lethal anaphylaxis, cardiac arrest, and brain death. Ultimately, DBS proteomics has the potential to provide stable and sensitive molecular data on envenomation syndromes and response pathways, which is particularly relevant in low-resource areas which may lack the materials for biofluid processing and storage.

Maternal dementia age at onset in relation to amyloid burden in non-demented elderly offspring.

Family history (FH) of dementia is a major risk factor for Alzheimer's disease, particularly when the FH is maternal and when the age of dementia onset (AO) is younger. This study tested whether brain amyloid-beta deposition, measured in vivo with (11)C-Pittsburgh compound B (PiB), was associated with parental dementia and/or younger parental AO. Detailed FH and positron emission tomography (PiB) data were acquired in 147 nondemented aging individuals (mean age 75 ± 8). No participant had both positive maternal and paternal FH. A series of analyses revealed that those with maternal, but not paternal, FH had greater levels of PiB retention in a global cortical region than those without FH. PiB retention in maternal FH was not significantly greater than paternal FH. Younger maternal dementia AO was related to greater PiB retention in offspring, whereas younger paternal dementia AO was not. Overall, results suggest that not only is amyloid-beta burden greater in individuals with maternal FH, but also that the burden is greater in association with younger maternal AO.

Tau positron emission tomographic imaging in aging and early Alzheimer disease.

OBJECTIVE: Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer disease (AD), staging and monitoring of disease progression, and development of disease-modifying therapies. METHODS: We acquired tau positron emission tomography (PET) using (18)F T807 (AV1451), and amyloid-ß PET using (11)C Pittsburgh compound B (PiB) in older clinically normal individuals, and symptomatic patients with mild cognitive impairment or mild AD dementia. RESULTS: We found abnormally high cortical (18)F T807 binding in patients with mild cognitive impairment and AD dementia compared to clinically normal controls. Consistent with the neuropathology literature, the presence of elevated neocortical (18)F T807 binding particularly in the inferior temporal gyrus was associated with clinical impairment. The association of cognitive impairment was stronger with inferior temporal (18)F T807 than with mean cortical (11)C PIB. Regional (18)F T807 was correlated with mean cortical (11)C PiB among both impaired and control subjects. INTERPRETATION: These findings suggest that (18)F T807 PET could have value as a biomarker that reflects both the progression of AD tauopathy and the emergence of clinical impairment.

Cognitive activity relates to cognitive performance but not to Alzheimer disease biomarkers.

OBJECTIVE: We aimed to determine whether there was a relationship between lifestyle factors and Alzheimer disease biomarkers. METHODS: In a cross-sectional study, we evaluated self-reported histories of recent and past cognitive activity, self-reported history of recent physical activity, and objective recent walking activity in 186 clinically normal individuals with mean age of 74 ± 6 years. Using backward elimination general linear models, we tested the hypotheses that greater cognitive or physical activity would be associated with lower Pittsburgh compound B-PET retention, greater (18)F-fluorodeoxyglucose-PET metabolism, and larger hippocampal volume, as well as better cognitive performance on neuropsychological testing. RESULTS: Linear regression demonstrated that history of greater cognitive activity was correlated with greater estimated IQ and education, as well as better neuropsychological testing performance. Self-reported recent physical activity was related to objective exercise monitoring. However, contrary to hypotheses, we did not find evidence of an association of Pittsburgh compound B retention, (18)F-fluorodeoxyglucose uptake, or hippocampal volume with past or current levels of cognitive activity, or with current physical activity. CONCLUSIONS: We conclude that a history of lifelong cognitive activity may support better cognitive performance by a mechanism that is independent of brain ß-amyloid burden, brain glucose metabolism, or hippocampal volume.

Regional fluorodeoxyglucose metabolism and instrumental activities of daily living across the Alzheimer's disease spectrum.

BACKGROUND: Impairment in instrumental activities of daily living (IADL) begins as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. IADL impairment in AD dementia has been associated with inferior parietal, inferior temporal, and superior occipital hypometabolism using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). OBJECTIVE: To investigate the relationship between regional FDG metabolism and IADL in clinically normal (CN) elderly, MCI, and mild AD dementia subjects cross-sectionally and longitudinally. METHODS: One hundred and four CN, 203 MCI, and 95 AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative underwent clinical assessments every 6 to 12 months for up to three years and baseline FDG PET. The subjective, informant-based Functional Activities Questionnaire was used to assess IADL. General linear models and mixed effects models were used, covarying for demographics, cognition, and behavior. RESULTS: The cross-sectional analysis revealed middle frontal and orbitofrontal hypometabolism were significantly associated with greater IADL impairment. Additionally, the interaction of diagnosis with posterior cingulate and with parahippocampal hypometabolism showed a greater decline in IADL performance as metabolism decreased for the AD dementia relative to the MCI group, and the MCI group relative to the CN group. The longitudinal analysis showed that baseline middle frontal and posterior cingulate hypometabolism were significantly associated with greater rate of increase in IADL impairment over time. CONCLUSION: These results suggest that regional synaptic dysfunction, including the Alzheimer-typical medial parietal and less typical frontal regions, relates to daily functioning decline at baseline and over time across the early AD spectrum.

Apathy is associated with increased amyloid burden in mild cognitive impairment.

Apathy is the most common neuropsychiatric symptom in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. The authors sought to determine whether apathy is associated with cortical amyloid burden, as measured by Pittsburgh Compound B (PiB) positron emission tomography (PET), and regional hypometabolism, measured by 18F-fluorodeoxyglocuse (FDG) PET in MCI. The authors found a significant association between increased apathy (lower Apathy Evaluation Scale score) and greater cortical PiB retention independent of age, but no significant association between apathy and regional FDG metabolism. These results suggest that increased apathy is associated with greater amyloid burden but not regional hypometabolism in MCI.

Subjective cognitive complaints and amyloid burden in cognitively normal older individuals.

Accumulating evidence suggests that subjective cognitive complaints (SCC) may indicate subtle cognitive decline characteristic of individuals with preclinical Alzheimer's disease (AD). In this study, we sought to build upon previous studies by associating SCC and amyloid-ß deposition using positron emission tomography with Pittsburgh Compound B (PiB-PET) in cognitively normal older individuals. One-hundred thirty one subjects (mean age 73.5±6) were administered three subjective cognitive questionnaires and a brief neuropsychological battery. A relationship between a subjective memory complaints composite score and cortical PiB binding was found to be significant, even after controlling for depressive symptoms. By contrast, there were no significant relationships between objective cognitive measures of memory and executive functions and cortical PiB binding. Our study suggests that SCC may be an early indicator of AD pathology detectable prior to significant objective impairment.

Free-ranging little brown myotis (Myotis lucifugus) heal from wing damage associated with white-nose syndrome.

White-nose syndrome (WNS) is having an unprecedented impact on hibernating bat populations in the eastern United States. While most studies have focused on widespread mortality observed at winter hibernacula, few have examined the consequences of wing damage that has been observed among those bats that survive hibernation. Given that WNS-related wing damage may lead to life-threatening changes in wing function, we tested the hypothesis that reduced abundance of free-ranging little brown myotis (Myotis lucifugus) with severe wing damage as the summer progresses is due to healing of wing tissue. Photographs of captured and recaptured adult females were examined for wing damage and healing rates were calculated for each category of wing damage index (WDI = 0-3). We found that free-ranging bats with severe wing damage were able to heal to a lower WDI score within 2 weeks. Bats with the most severe wing damage had faster healing rates than did individuals with less damage. We also found a significant relationship between body condition and WDI for adult females captured in the early weeks of the active season. Our results support the hypothesis that some bats can heal from severe wing damage during the active season, and thus may not experience increased mortality associated with reduced functions of wings. We urge researchers and wildlife managers to use caution when interpreting data on WDI to assess the impact of WNS on bat populations, especially during the later months of the active season.