Continuous Quality Improvement: Utilizing a Novel Education Platform to Enhance Care for the Caregiver in the Neurosciences Intensive Care Unit.

Background: Timely patient and family communication is fundamental to the delivery of patient and family-centered care in the intensive care unit (ICU). However, repetitive, non-urgent communication with patients and designated patient contacts (DPCs) may lead to workflow disruptions, patient safety concerns and burnout. Implementing media-rich, educational content via a web-app could promote a more communication-friendly environment and reduce redundant communication. This may lower workflow disruptions and save time for more meaningful interactions with providers. The goal of this study was to deliver relevant, high-quality content via a web-app, assess time savings, and patient satisfaction with the web-app. Methods: A pre-implementation survey was distributed to Neurosciences intensive care unit (NSICU) staff to assess the burden of repetitive non-urgent communication and perceived duration of disruptions. Patients admitted to the NSICU from September 2022 to February 2023, n = 221 were included in the study. Patients were enrolled in the web-app. Patients and their DPC were granted access. Demographics including patient diagnosis, age, gender, and race were collected, along with data on weekly patient enrollment, number of DPCs granted access, total, frequency, and average view times of each piece of web-app content, and expected time saved due to review of web-app-based content by patient and/or DPCs to reduce repetitive communication by NSICU caregivers. The time saved for each piece of web-app content was calculated after getting feedback from providers (attendings, fellows, advanced practice providers, nurses) for how long it generally took them to convey each piece of information to patients and families. Results: Based on web-app content reviewed by patients and/or DPCs, the estimated average amount of NSICU caregiver time saved over the study period, based on application content views, was 82 min per week, and the cumulative total provider time saved for all content views was 26 h and 53 min. Twenty-one of 59 applications were rated by patients or their DPC and received five-star reviews (out of 5). Conclusion: The implementation of a web-app to facilitate and increase efficiency in communication leads to time savings for NSICU providers and patient/DPC satisfaction with the media-rich educational content.

The co-occurrence of dementia in those with epilepsy is associated with 30-day readmission - A population-based study.

OBJECTIVE: Dementia and epilepsy often co-occur and are associated with poor health outcomes and increased healthcare utilization. The literature on the association between readmission and co-occurrence of dementia and epilepsy is scant. Our objective was to determine if dementia in patients with epilepsy >40 years old is associated with 30-day hospital readmission, in-hospital mortality, discharge disposition, and length-of-stay. METHODS: This retrospective cohort study used the 2014 Nationwide Readmissions Database, containing data from hospital discharges across the US and readmissions. Epilepsy and dementia were identified using previously validated ICD-9-CM codes. Primary outcome was 30-day readmission, analyzed with univariable and multivariable logistic regressions. Secondary outcomes were discharge disposition, in-hospital mortality, and length-of-stay, analyzed with univariable multinomial logistic, univariable logistic, and univariable ordinary least squared regressions, respectively. The top ten causes of readmission in each group were compared as well. All analyses accounted for survey weights, cluster, and stratum. RESULTS: Patients with epilepsy with dementia (n = 15,588) had longer hospital stays [15% (95%CI 10-20%)], and higher odds of readmission [OR 1.11 (95%CI 1.05-1.17)], transfer to another facility [OR 2.18 (95%CI 1.93-2.46)], and in-hospital mortality [OR 1.50 (95%CI 1.25-1.79)] compared to those without dementia (n = 186,289).The top two causes of readmission were septicemia (dementia: 14.81%; no dementia: 9.45%) and epilepsy/convulsions (dementia: 5.91%; no dementia: 6.25%). Other top 10 causes of readmissions in those with epilepsy and dementia which were not present in those without dementia included delirium (5.21%), urinary tract infections (4.98%), and aspiration pneumonitis (4.29%). SIGNIFICANCE: Dementia in epilepsy is associated with worse outcomes, including higher in-hospital mortality and higher readmissions. Potentially preventable causes of readmission in those with epilepsy and dementia were identified, including septicemia, delirium, urinary tract infection, and aspiration pneumonitis. Future studies are needed to inform interventions aimed at decreasing premature mortality and reducing potentially preventable readmissions in this vulnerable population.

A Case of Elsberg Syndrome in the Setting of Asymptomatic SARS-CoV-2 Infection.

ABSTRACT: Elsberg syndrome is a rare cause of lumbosacral radiculitis with concomitant thoracic and lumbosacral myelitis that can be seen after an acute or reactivated viral infection. After the initial coronavirus surge in New York City, a 68-year-old man developed progressive lower extremity weakness and a defined sensory level at the lower abdomen. He had highly elevated SARS-CoV-2 IgG antibodies despite an absence of preceding COVID-19 symptoms. Serial electrodiagnostic testing revealed absent lower extremity late responses, with otherwise normal distal sensorimotor conductions. Electromyography revealed active neurogenic changes and reduced motor unit recruitment in the L3-L4 myotomes. Treatment with methylprednisolone and intravenous immunoglobulin was followed by minimal clinical improvement but re-emergence of the lower extremity late responses on electrodiagnostic testing. We report here, to the best of our knowledge, the first case of suspected COVID-19-associated Elsberg syndrome, which expands the spectrum of neuromuscular manifestations associated with SARS-CoV-2 infection and sheds light on ways to approach diagnostic and treatment options for these patients.

Selective Targeting by a Mechanism-Based Inactivator against Pyridoxal 5'-Phosphate-Dependent Enzymes: Mechanisms of Inactivation and Alternative Turnover.

Potent mechanism-based inactivators can be rationally designed against pyridoxal 5'-phosphate (PLP)-dependent drug targets, such as ornithine aminotransferase (OAT) or γ-aminobutyric acid aminotransferase (GABA-AT). An important challenge, however, is the lack of selectivity toward other PLP-dependent, off-target enzymes, because of similarities in mechanisms of all PLP-dependent aminotransferase reactions. On the basis of complex crystal structures, we investigate the inactivation mechanism of OAT, a hepatocellular carcinoma target, by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP), a known inactivator of GABA-AT. A crystal structure of OAT and FCP showed the formation of a ternary adduct. This adduct can be rationalized as occurring via an enamine mechanism of inactivation, similar to that reported for GABA-AT. However, the crystal structure of an off-target, PLP-dependent enzyme, aspartate aminotransferase (Asp-AT), in complex with FCP, along with the results of attempted inhibition assays, suggests that FCP is not an inactivator of Asp-AT, but rather an alternate substrate. Turnover of FCP by Asp-AT is also supported by high-resolution mass spectrometry. Amid existing difficulties in achieving selectivity of inactivation among a large number of PLP-dependent enzymes, the obtained results provide evidence that a desirable selectivity could be achieved, taking advantage of subtle structural and mechanistic differences between a drug-target enzyme and an off-target enzyme, despite their largely similar substrate binding sites and catalytic mechanisms.

PLP and GABA trigger GabR-mediated transcription regulation in Bacillus subtilis via external aldimine formation.

The Bacillus subtilis protein regulator of the gabTD operon and its own gene (GabR) is a transcriptional activator that regulates transcription of γ-aminobutyric acid aminotransferase (GABA-AT; GabT) upon interactions with pyridoxal-5'-phosphate (PLP) and GABA, and thereby promotes the biosynthesis of glutamate from GABA. We show here that the external aldimine formed between PLP and GABA is apparently responsible for triggering the GabR-mediated transcription activation. Details of the "active site" in the structure of the GabR effector-binding/oligomerization (Eb/O) domain suggest that binding a monocarboxylic γ-amino acid such as GABA should be preferred over dicarboxylic acid ligands. A reactive GABA analog, (S)-4-amino-5-fluoropentanoic acid (AFPA), was used as a molecular probe to examine the reactivity of PLP in both GabR and a homologous aspartate aminotransferase (Asp-AT) from Escherichia coli as a control. A comparison between the structures of the Eb/O-PLP-AFPA complex and Asp-AT-PLP-AFPA complex revealed that GabR is incapable of facilitating further steps of the transamination reaction after the formation of the external aldimine. Results of in vitro and in vivo assays using full-length GabR support the conclusion that AFPA is an agonistic ligand capable of triggering GabR-mediated transcription activation via formation of an external aldimine with PLP.