Reduction of benztropine use duration in acute psychiatry: A quality improvement initiative.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Secondary to the risk of antipsychotic-induced acute dystonia, prophylactic use of benztropine is occasionally warranted but is recommended for no longer than 7 days after initiating an antipsychotic, correlating to the period of highest dystonia risk. Despite the associated increased anticholinergic burden, many clinicians continue to order benztropine for periods exceeding the recommended prophylactic duration. We investigated the reduction of benztropine use duration subsequent to implementation of truncated electronic entry orders to improve benztropine prescribing within an acute psychiatric facility. METHODS: Data were collected for psychiatric inpatients admitted between January and June 2020 who were prescribed scheduled benztropine. In a quality improvement initiative implemented in April 2022, electronic orders for benztropine were modified from a 180-day to a 7-day duration, with subsequent postintervention data collection. The primary outcomes included a change in the duration of benztropine use for any indication in the hospital, and a change in the percentage of patients meeting predetermined "unnecessary use" criteria. Secondary analyses included the percentage of patients with discharge prescriptions for scheduled benztropine (either for prophylaxis or for other indications) in the pre- and postintervention periods. RESULTS: 73 pre- and 77 postintervention individual patients/encounters were included. Following the intervention, in-hospital duration of benztropine use for any indication decreased from a median of 14 days to a median of 7.5 days (P < 0.05), and appropriate use increased by 92.9%. The percentage of patients with prescriptions for scheduled benztropine decreased from 67.1% in the preintervention group to 29.9% in the postintervention group. CONCLUSION: Decreased benztropine use duration, by means of truncated order entry sentences, during inpatient psychiatric admissions, appears feasible regardless of dual antipsychotic or first-generation antipsychotic use, and may reduce the rates of benztropine prescriptions written for discharge.

The Effect of Social Drivers of Health on 90-Day Readmission Rates and Costs After Primary Total Hip and Total Knee Arthroplasty.

INTRODUCTION: The effect of social drivers of health (SDOH) on readmissions and costs after total hip arthroplasty (THA) and total knee arthroplasty (TKA) is poorly understood. Policies such as the Hospital Readmissions Reduction Program have targeted overall readmission reduction, using value-based strategies to improve healthcare quality. However, the implications of SDOH on these outcomes are not yet understood. We hypothesized that the area deprivation index (ADI) as a surrogate for SDOH would markedly influence readmission rates and healthcare costs in the 90-day postprocedural period for THA and TKA. METHODS: We used the 100% US fee-for-service Medicare claims data from 2019 to 2021. Patients were identified using diagnosis-related groups. Our primary outcomes included 90-day unplanned readmission after hospital discharge and cost of care, treated as "high cost" if > 1 standard deviation above the mean. The relationships between ADI and primary outcomes were estimated with logistic regression models. RESULTS: A total of 628,399 patients were included in this study. The mean age of patients was 75.6, 64% were female, and 7.8% were dually eligible for Medicaid. After full covariate adjustment, readmission was higher for patients in more deprived areas (high Area Deprivation Index (ADI)) (low socioeconomic status (SES) group OR: 1.30 [95% confidence intervals 1.23, 1.38]). ADI was associated with high cost before adjustment (low SES group odds ratio 1.08 [95% confidence intervals 1.04, 1.11], P < 0.001), although, after adjustment, this association was lost. DISCUSSION: This analysis highlights the effect of SDOH on readmission rates after THA and TKA. A nuanced understanding of neighborhood-level disparities may facilitate targeted strategies to reduce avoidable readmissions in orthopaedic surgery. Regarding cost, although there is some association between ADI and cost, this study may illustrate that ADI for THA and TKA is not sufficiently granular to identify the contribution of social drivers to elevated costs.

Nonterpenoid Chemical Diversity of Cannabis Phenotypes Predicts Differentiated Aroma Characteristics.

The recent increase in legality of Cannabis Sativa L. has led to interest in developing new varieties with unique aromatic or effect-driven traits. Selectively breeding plants for the genetic stability and consistency of their secondary metabolite profiles is one application of phenotyping. While this horticultural process is used extensively in the cannabis industry, few studies exist examining the chemical data that may differentiate phenotypes aromatically. To gain insight into the diversity of secondary metabolite profiles between progeny, we analyzed five ice water hash rosin extracts created from five different phenotypes of the same crossing using comprehensive 2-dimensional gas chromatography coupled to time-of-flight mass spectrometry, flame ionization detection, and sulfur chemiluminescence detection. These results were then correlated to results from a human sensory panel, which revealed specific low-concentration compounds that strongly influence sensory perception. We found aroma differences between certain phenotypes that are driven by key minor, nonterpenoid compounds, including the newly reported 3-mercaptohexyl hexanoate. We further report the identification of octanoic and decanoic acids, which are implicated in the production of cheese-like aromas in cannabis. These results establish that even genetically similar phenotypes can possess diverse and distinct aromas arising not from the dominant terpenes, but rather from key minor volatile compounds. Moreover, our study underscores the value of detailed chemical analyses in enhancing cannabis selective breeding practices, offering insights into the chemical basis of aroma and sensory differences.

Current Strengths and Weaknesses of ChatGPT as a Resource for Radiation Oncology Patients and Providers.

PURPOSE: Chat Generative Pre-Trained Transformer (ChatGPT), an artificial intelligence program that uses natural language processing to generate conversational-style responses to questions or inputs, is increasingly being used by both patients and health care professionals. This study aims to evaluate the accuracy and comprehensiveness of ChatGPT in radiation oncology-related domains, including answering common patient questions, summarizing landmark clinical research studies, and providing literature reviews with specific references supporting current standard-of-care clinical practice in radiation oncology. METHODS AND MATERIALS: We assessed the performance of ChatGPT version 3.5 (ChatGPT3.5) in 3 areas. We evaluated ChatGPT3.5's ability to answer 28 templated patient-centered questions applied across 9 cancer types. We then tested ChatGPT3.5's ability to summarize specific portions of 10 landmark studies in radiation oncology. Next, we used ChatGPT3.5 to identify scientific studies supporting current standard-of-care practice in clinical radiation oncology for 5 different cancer types. Each response was graded independently by 2 reviewers, with discordant grades resolved by a third reviewer. RESULTS: ChatGPT3.5 frequently generated inaccurate or incomplete responses. Only 39.7% of responses to patient-centered questions were considered correct and comprehensive. When summarizing landmark studies in radiation oncology, 35.0% of ChatGPT3.5's responses were accurate and comprehensive, improving to 43.3% when provided the full text of the study. ChatGPT3.5's ability to present a list of studies related to standard-of-care clinical practices was also unsatisfactory, with 50.6% of the provided studies fabricated. CONCLUSIONS: ChatGPT should not be considered a reliable radiation oncology resource for patients or providers at this time, as it frequently generates inaccurate or incomplete responses. However, natural language programming-based artificial intelligence programs are rapidly evolving, and future versions of ChatGPT or similar programs may demonstrate improved performance in this domain.

Contribution of Clinical Trial Event Data by Data Source: A Prespecified Analysis of the ADAPTABLE Randomized Clinical Trial.

Importance: Pragmatic randomized clinical trials (RCTs) often use multiple data sources to examine clinical events, but the relative contribution of data sources to clinical end-point rates is understudied. Objective: To assess the contribution of data sources (electronic health records [EHRs], public/private insurance claims, and/or participant-reported data) to clinical end points among ADAPTABLE participants who had available data. Design, Setting, and Participants: The ADAPTABLE study was an open-label, pragmatic RCT from April 2016 through June 2019 conducted in research networks within clinical practice. Participants had existing atherosclerotic cardiovascular disease and available data to analyze. The characteristics of patients by combinations of data source availability were compared to examine the contribution of each of the data sources to end-point ascertainment. Data for this prespecified analysis were examined from January 2022 to June 2023. Exposures: Randomized exposure to 81 mg or 325 mg of aspirin daily. Main Outcomes and Measures: Number of events for the primary end point (composite of death, hospitalization for myocardial infarction, and hospitalization for stroke) that were contributed by EHR or claims data and then number of events contributed by each additional data source. Results: Of 15 006 participants randomized with at least 1 other source of data available beyond participant-reported data, there were 8756 (58.3%) with participant-reported and EHR data; 4291 (28.6%) with participant-reported, EHR, and claims data; 1412 (9.4%) with EHR-only data; 262 (1.7%) with participant-reported and claims data; 202 (1.3%) with EHR and claims data; and 83 (0.6%) with claims-only data. Participants with EHR-only data were younger (median age, 63.7 years; IQR, 55.8-71.4) compared with the other groups (range, 65.6-71.9 years). Among participants with both EHR and claims data, with or without participant-reported data (n = 4493), for each outcome, most events (92%-100%) were identified in the EHR or in claims data. For all clinical end points, participant-reported data contributed less than 10% of events not otherwise available from claims or EHR data. Conclusions and Relevance: In this analysis of a pragmatic RCT, claims and EHR data provided the most clinical end-point data when compared with participant-reported events. These findings provide a framework for collecting end points in pragmatic clinical trials. Further work is needed to understand the data source combinations that most effectively provide clinical end-point data in RCTs.

Sublingual asenapine for agitation in malabsorptive states: three patient cases.

Gastric malabsorptive conditions may prevent patients from deriving benefit from orally administered medications intended for enteric absorption. While malabsorption is an increasingly common issue, current data on alternative oral options for agitation in these patients are very sparse. Sublingual (SL) asenapine is absorbed transmucosally, bypassing gut absorption, making it a viable consideration. We report on three patients, one with short bowel syndrome, one with viral gastritis, and one with aortic dissection who were trialed on SL asenapine for agitation after failing alternative antipsychotics. Two of these patients had an extensive history of psychiatric admissions for bipolar disorder and substance-induced psychosis. All three patients had significant reductions in agitation within 1-5 days, with no reported adverse effects. However, benefit of SL asenapine was hindered in two of these patients as they began inappropriately swallowing the medication, reducing bioavailability to nil. Clinicians should consider the use of SL asenapine for medically complex agitated patients where gastric absorption is questionable. There is an urgent need for guidelines on this matter, as well as more, alternative dosage forms for various medications that may help with agitation in this population.

Mesial temporal lobe spiking reveals distinct patterns of blood oxygen level-dependent functional magnetic resonance imaging activation using simultaneous intracranial electroencephalography-functional magnetic resonance imaging.

OBJECTIVE: Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography-functional MRI (iEEG-fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED-associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE. METHODS: Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG-fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED-associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation. RESULTS: Two patterns of IED-associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic-clonic seizures and had better postsurgical outcomes. SIGNIFICANCE: Simultaneous iEEG-fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED-associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated-activation had fewer focal to bilateral tonic-clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events.

Treatment of sebaceous carcinoma with Mohs micrographic surgery versus wide local excision: a systematic review.

Sebaceous carcinoma (SC) is a rare neoplasm affecting periocular and extraocular sites. If inadequately treated, it can recur and cause morbidity. Specific management guidelines have not been established. Wide local excision (WLE) has been traditionally used; however, Mohs micrographic surgery (MMS) can be advantageous because of complete margin assessment and tissue-sparing nature. This analysis aims to systematically review the surgical modalities used for the management of SC. Articles meeting eligibility criteria were identified using MEDLINE (via PubMed), Embase, Cochrane, and Scopus databases. All studies investigating surgical management of SC with WLE or MMS were considered. Seventy studies met inclusion criteria, including retrospective cohort studies, case series, and case reports. WLE was used in 32 studies, MMS in 29, and MMS and WLE in 9. Subgroup analysis showed that MMS has lower recurrence rates. For WLE, local, regional, and distant recurrence rates were 23.4%, 13.3%, and 11.0%, respectively, and for MMS, 6.8%, 4.3%, and 4.6%, respectively. Patients treated with WLE were more likely to have local recurrence than patients treated with MMS (P = 0.001). WLE cases were more likely to have a regional (P = 0.05) and distant recurrence (P = 0.001). Limitations of the study include heterogeneity of case reports, case series, and retrospective studies, variable follow-up times between the two groups, and large tumors included in the WLE category. In addition, disease-specific survival was not evaluated. MMS cases showed a superior outcome for local, regional, and distant recurrence, making it a good option for the management of SC.

Diffusion MRI of the Hippocampus.

The hippocampus is a brain structure that plays key roles in a variety of cognitive processes. Critically, a wide range of neurological disorders are associated with degeneration of the hippocampal microstructure, defined as neurons, dendrites, glial cells, and more. Thus, the hippocampus is a key target for methods that are sensitive to these microscale properties. Diffusion MRI is one such method, which can noninvasively probe neural architecture. Here we review the extensive use of diffusion MRI to capture hippocampal microstructure in both health and disease. The results of these studies indicate that (1) diffusion tensor imaging is sensitive but not specific to the hippocampal microstructure; (2) biophysical modeling of diffusion MRI signals is a promising avenue to capture more specific aspects of the hippocampal microstructure; (3) use of ultra-short diffusion times have shown unique laminar-specific microstructure and response to hippocampal injury; (4) dispersion of microstructure is likely abundant in the hippocampus; and (5) the angular richness of the diffusion MRI signal can be leveraged to improve delineation of the internal hippocampal circuitry. Overall, extant findings suggest that diffusion MRI offers a promising avenue for characterizing hippocampal microstructure.

Association of Psychological Resilience, Cognitive Reserve, and Brain Reserve with Post-Concussive Symptoms in Children with Mild Traumatic Brain Injury and Orthopedic Injury: An A-CAP Study.

Protective factors, including psychological resilience, cognitive reserve, and brain reserve, may be positively associated with recovery after pediatric mild traumatic brain injury (mTBI) but are yet to be studied concurrently. We sought to examine these factors as moderators of post-concussive symptoms (PCS) in pediatric mTBI compared with mild orthopedic injury (OI). Participants included 967 children (633 mTBI, 334 OI) aged 8-16.99 years, recruited from 5 Canadian pediatric emergency departments as part of a prospective longitudinal cohort study. At 10 days post-injury, psychological resilience was measured using the Connor-Davidson Resilience Scale and brain reserve was measured using total brain volume derived from structural magnetic resonance imaging. Cognitive reserve was measured at 3 months post-injury using IQ scores from the Wechsler Abbreviated Scale of Intelligence-Second Edition. Cognitive and somatic PCS were measured using child and parent ratings on the Health and Behavior Inventory, completed weekly for 3 months and biweekly to 6 months. Analyses involved generalized least-squares regression models using restricted cubic splines. Covariates included age at injury, sex, racialized identity, material and social deprivation, pre-injury migraine and concussion history, and retrospective pre-injury PCS. Psychological resilience moderated group differences in parent-reported PCS. At 30 days post-injury, estimated group differences in parent-reported cognitive and somatic PCS (mTBI > OI) were larger at higher (75th percentile) resilience scores (Est = 2.25 [0.87, 3.64] and Est = 2.38 [1.76, 3.00], respectively) than at lower (25th percentile) resilience scores (Est = 1.44 [0.01, 2.86] and Est = 2.08 [1.45, 2.71], respectively). Resilience did not moderate group differences in child-reported PCS but was negatively associated with child-reported PCS in both groups (ps ≤ 0.001). Brain reserve (i.e., total brain volume [TBV]) also moderated group differences, but only for parent-reported somatic PCS (p = 0.018). Group difference (mTBI > OI) at 30 days was larger at smaller (25th percentile) TBV (Est = 2.78 [2.17, 3.38]) than at larger (75th percentile) TBV (Est = 1.95 [1.31, 2.59]). TBV was not associated with parent-reported cognitive PCS or child-reported PCS. IQ did not moderate PCS in either group but had a significant non-linear association in both groups with child-reported somatic PCS (p = 0.018) and parent-reported PCS (p < 0.001), with higher PCS scores at both lower and higher IQs. These findings suggest that higher resilience predicts fewer PCS, but less strongly after mTBI than OI; greater brain reserve may reduce the effect of mTBI on somatic PCS; and cognitive reserve has an unexpected curvilinear association with PCS across injury types. The results highlight the importance of protective factors as predictors of recovery and potential targets for intervention following pediatric mTBI.

Engagement-free and Contactless Bed Occupancy and Vital Signs Monitoring.

This paper presents the design and evaluation of an engagement-free and contactless vital signs and occupancy monitoring system called BedDot. While many existing works demonstrated contactless vital signs estimation, they do not address the practical challenge of environment noises, online bed occupancy detection and data quality assessment in the realworld environment. This work presents a robust signal quality assessment algorithm consisting of three parts: bed occupancy detection, movement detection, and heartbeat detection, to identify high-quality data. It also presents a series of innovative vital signs estimation algorithms that leverage the advanced signal processing and Bayesian theorem for contactless heart rate (HR), respiration rate (RR), and inter-beat interval (IBI) estimation. The experimental results demonstrate that BedDot achieves over 99% accuracy for bed occupancy detection, and MAE of 1.38 BPM, 1.54 BPM, and 24.84 ms for HR, RR, and IBI estimation, respectively, compared with an FDA-approved device. The BedDot system has been extensively tested with data collected from 75 subjects for more than 80 hours under different conditions, demonstrating its generalizability across different people and environments.

Aggressive Treatment Strategy at Index Thoracic Endovascular Aortic Surgery is Associated with Reduced Need for Short-Term Reintervention in Patients with Aortic Dissection.

INTRODUCTION: Thoracic endovascular aortic surgery (TEVAR) is the modern standard of treatment for patients with Type B aortic dissection, however it is unclear how the initial length of treated aorta affects long-term outcomes. This study aims to elucidate risk factors for secondary intervention after TEVAR for aortic dissection, focusing on length of aortic treatment at index operation. METHODS: A retrospective multihospital chart review was completed for patients treated between 2011 and 2022 who underwent TEVAR for aortic dissection with at least 1 year of post-TEVAR imaging and follow-up. Patient demographics and characteristics were analyzed. In this study, aortic zones treated only included those managed with a covered stent graft. The primary outcome measure was any need for secondary intervention. RESULTS: A total of 151 patients were identified. Demographics included a mean age of 57 years, with 31.8% of the patients being female. Forty-three patients (28.5%) underwent secondary intervention after TEVAR, with a mean follow-up of 1.6 years. The most common indication for secondary intervention was aneurysmal degeneration of the residual false lumen (76%). There was a significant difference in the number of aortic zones treated in patients who did and did not require secondary intervention (2.3 ± 1 vs. 2.7 ± 1, P = 0.04). Additionally, patients with 3 or more aortic zones of treatment had a significant difference in the need for reintervention (32% secondary intervention versus 52% no secondary intervention, P = 0.02). CONCLUSIONS: At least 3 zones of aortic treatment at index TEVAR is associated with a decreased need for overall reintervention. Modern treatment of acute and subacute type B dissection should stress an aggressive initial repair, balanced by the potential increased risk of spinal cord ischemia.

A Principled Approach to Characterize and Analyze Partially Observed Confounder Data from Electronic Health Records.

Objective: Partially observed confounder data pose challenges to the statistical analysis of electronic health records (EHR) and systematic assessments of potentially underlying missingness mechanisms are lacking. We aimed to provide a principled approach to empirically characterize missing data processes and investigate performance of analytic methods. Methods: Three empirical sub-cohorts of diabetic SGLT2 or DPP4-inhibitor initiators with complete information on HbA1c, BMI and smoking as confounders of interest (COI) formed the basis of data simulation under a plasmode framework. A true null treatment effect, including the COI in the outcome generation model, and four missingness mechanisms for the COI were simulated: completely at random (MCAR), at random (MAR), and two not at random (MNAR) mechanisms, where missingness was dependent on an unmeasured confounder and on the value of the COI itself. We evaluated the ability of three groups of diagnostics to differentiate between mechanisms: 1)-differences in characteristics between patients with or without the observed COI (using averaged standardized mean differences [ASMD]), 2)-predictive ability of the missingness indicator based on observed covariates, and 3)-association of the missingness indicator with the outcome. We then compared analytic methods including "complete case", inverse probability weighting, single and multiple imputation in their ability to recover true treatment effects. Results: The diagnostics successfully identified characteristic patterns of simulated missingness mechanisms. For MAR, but not MCAR, the patient characteristics showed substantial differences (median ASMD 0.20 vs 0.05) and consequently, discrimination of the prediction models for missingness was also higher (0.59 vs 0.50). For MNAR, but not MAR or MCAR, missingness was significantly associated with the outcome even in models adjusting for other observed covariates. Comparing analytic methods, multiple imputation using a random forest algorithm resulted in the lowest root-mean-squared-error. Conclusion: Principled diagnostics provided reliable insights into missingness mechanisms. When assumptions allow, multiple imputation with nonparametric models could help reduce bias.

Extended thoracic endovascular aortic repair is optimal therapy in acute complicated type B dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) represents optimal therapy for complicated acute type B aortic dissection (aTBAD). Persistent knowledge gaps remain, including the optimal length of aortic coverage, impact on distal aortic remodeling, and fate of the dissected abdominal aorta. METHODS: Review of the Emory Aortic Database identified 92 patients who underwent TEVAR for complicated aTBAD from 2012 to 2018. Standard TEVAR covered aortic zones 3 and 4 (from the left subclavian to the mid-descending thoracic aorta). Extended TEVAR fully covered aortic zones 3 though 5 (from the left subclavian to the celiac artery). Long-term imaging, clinical follow-up, and overall and aortic-specific mortality were reviewed. RESULTS: Extended TEVAR (n = 52) required a greater length of coverage vs standard TEVAR (n = 40) (240 ± 32 mm vs 183 ± 23 mm; P < .01). In-hospital mortality occurred in 5.4% of patients (7.7% vs 2.5%; P = .27) owing to mesenteric malperfusion (n = 3) or rupture (n = 2). The overall incidences of postoperative stroke, transient paraparesis, paraplegia, and dialysis were 5.4% (3.9% vs 7.5%; P = .38), 3.2% (5.8% vs 0%; P = .18), 0%, and 0% respectively, equivalent between groups. Follow-up was 96.6% complete to a mean of 6.1 years (interquartile range, 3.5-8.6 years). There were significantly higher rates of complete thrombosis or obliteration of the entire thoracic false lumen after Extended TEVAR (82.2% vs 51.5%; P = .04). Distal aortic reinterventions were less frequent after extended TEVAR (5.8% vs 20%; P = .04). Late aorta-specific survival was 98.1% after extended TEVAR vs 92.3% for standard TEVAR (P = .32). CONCLUSIONS: Extended TEVAR for complicated aTBAD is safe, results in a high rate of total thoracic false lumen thrombosis/obliteration, and reduces distal reinterventions. Longer-term follow-up will be needed to demonstrate a survival benefit compared to limited aortic coverage.

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.

BACKGROUND: Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes. METHODS: In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery. FINDINGS: The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors. INTERPRETATION: Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment. FUNDING: US National Institutes of Health.

Structural network topology associated with naming improvements following intensive aphasia therapy in post-stroke aphasia.

A stroke can disrupt the finely tuned language network resulting in aphasia, a language impairment. Though many stroke survivors with aphasia recover within the first 6 months, a significant proportion have lasting deficits. The factors contributing to optimal treatment response remain unclear. Some evidence suggests that increased modularity or fragmentation of brain networks may underlie post-stroke aphasia severity and the extent of recovery. We examined associations between network organization and aphasia recovery in sixteen chronic stroke survivors with non-fluent aphasia following 35 h of Multi-Modality Aphasia Therapy over 10 days and 20 healthy controls who underwent imaging at a single timepoint. Using diffusion-weighted scans obtained before and after treatment, we constructed whole-brain structural connectomes representing the number of probabilistic streamlines between brain regions. Graph theory metrics were quantified for each connectome using the Brain Connectivity Toolbox. Correlations were examined between graph metrics and speech performance measured using the Boston Naming Test (BNT) at pre-, post- and 3-months post-intervention. Compared to controls, participants with stroke demonstrated higher whole-brain modularity at pre-treatment. Modularity did not differ between pre- and post-treatment. In individuals who responded to therapy, higher pre-treatment modularity was associated with worse performance on the BNT. Moreover, higher pre-treatment participation coefficients (i.e., how well a region is connected outside its own module) for the left IFG, planum temporale, and posterior temporal gyri were associated with greater improvements at post-treatment. These results suggest that pre-treatment network topology may impact therapeutic gains, highlighting the influence of network organization on post-stroke aphasia recovery.

Long-term outcomes after recurrent acute thoracic aortic dissection: Insights from the International Registry of Aortic Dissection.

OBJECTIVE: With an aging population and advancements in imaging, recurrence of thoracic aortic dissection is becoming more common. METHODS: All patients enrolled in the International Registry of Aortic Dissection from 1996 to 2023 with type A and type B acute aortic dissection were identified. Among them, initial dissection and recurrent dissection were discerned. The study period was categorized into 3 eras: historic era, 1996 to 2005; middle era, 2006 to 2015; most recent era, 2016 to 2023. Propensity score matching was applied between initial dissection and recurrent dissection. Outcome of interests included long-term survival and cumulative incidence of major aortic events defined by the composite of reintervention, aortic rupture, and new dissection. RESULTS: The proportion of recurrent dissection increased from 5.9% in the historic era to 8.0% in the most recent era in the entire dissection cohort. In patients with type A dissection, propensity score matching between initial dissection and recurrent dissection yielded 326 matched pairs. Kaplan-Meier curves showed similar long-term survival between the 2 groups. However, the cumulative incidence of major aortic events was significantly higher in the recurrent dissection group (40.3% ± 6.2% vs 17.8% ± 5.1% at 4 years in the initial dissection group, P = .02). For type B dissection, 316 matched pairs were observed after propensity score matching. Long-term survival and the incidence of major aortic events were equivalent between the 2 groups. CONCLUSIONS: The case volume of recurrent dissection or the ability to detect recurrent dissection has increased over time. Acute type A recurrent dissection was associated with a higher risk of major aortic events than initial dissection. Further judicious follow-up may be crucial after type A recurrent dissection.

New-Onset Prolonged Psychosis Following Synthetic Cannabinoid Use in an Older Patient: A Case Report.

Synthetic cannabinoids (SCs), a class of new psychoactive substances (NPS) commonly known as "spice," has rapidly gained popularity and become the most ubiquitous NPS on the illegitimate drug market. SCs, unlike natural cannabis (NC), are not controlled by international drug conventions, posing a significant risk to public health. These substances are easily accessible, relatively inexpensive, and challenging to detect in routine drug screenings. The existing literature provides strong evidence of an association between NC use and psychosis, but there is significantly less data on SC psychosis. We present a clinical case report of a 51-year-old African American female with no known psychiatric history who was admitted to the inpatient psychiatric unit after reported paranoia and altered mental status for the preceding six days. During hospitalization, she exhibited disorganization, persecutory delusions, extreme agitation, and bizarre behaviors that included the concealment of a set of stolen keys in her vagina, necessitating an ethics consult. After consideration of differentials, the patient was diagnosed with substance-induced psychotic disorder secondary to SC. The patient was stabilized on 3 mg Risperidone at bedtime. After 16-day hospitalization, she reached her baseline and later revealed that she had recently smoked SC for the first time. The primary goal of this case is to highlight the sequelae of SC-associated psychosis. A SC-associated psychosis could drastically vary from NC and is often undetectable on a typical UDS, which may result in a lifelong primary psychotic disorder misdiagnosis.

Deep EEG source localization via EMD-based fMRI high spatial frequency.

Brain imaging with a high-spatiotemporal resolution is crucial for accurate brain-function mapping. Electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI) are two popular neuroimaging modalities with complementary features that record brain function with high temporal and spatial resolution, respectively. One popular non-invasive way to obtain data with both high spatial and temporal resolutions is to combine the fMRI activation map and EEG data to improve the spatial resolution of the EEG source localization. However, using the whole fMRI map may cause spurious results for the EEG source localization, especially for deep brain regions. Considering the head's conductivity, deep regions' sources with low activity are unlikely to be detected by the EEG electrodes at the scalp. In this study, we use fMRI's high spatial-frequency component to identify the local high-intensity activations that are most likely to be captured by the EEG. The 3D Empirical Mode Decomposition (3D-EMD), a data-driven method, is used to decompose the fMRI map into its spatial-frequency components. Different validation measurements for EEG source localization show improved performance for the EEG inverse-modeling informed by the fMRI's high-frequency spatial component compared to the fMRI-informed EEG source-localization methods. The level of improvement varies depending on the voxels' intensity and their distribution. Our experimental results also support this conclusion.