Bayesian Sparse Regression Analysis Documents the Diversity of Spinal Inhibitory Interneurons.

Documenting the extent of cellular diversity is a critical step in defining the functional organization of tissues and organs. To infer cell-type diversity from partial or incomplete transcription factor expression data, we devised a sparse Bayesian framework that is able to handle estimation uncertainty and can incorporate diverse cellular characteristics to optimize experimental design. Focusing on spinal V1 inhibitory interneurons, for which the spatial expression of 19 transcription factors has been mapped, we infer the existence of ~50 candidate V1 neuronal types, many of which localize in compact spatial domains in the ventral spinal cord. We have validated the existence of inferred cell types by direct experimental measurement, establishing this Bayesian framework as an effective platform for cell-type characterization in the nervous system and elsewhere.

Spinal Inhibitory Interneuron Diversity Delineates Variant Motor Microcircuits.

Animals generate movement by engaging spinal circuits that direct precise sequences of muscle contraction, but the identity and organizational logic of local interneurons that lie at the core of these circuits remain unresolved. Here, we show that V1 interneurons, a major inhibitory population that controls motor output, fractionate into highly diverse subsets on the basis of the expression of 19 transcription factors. Transcriptionally defined V1 subsets exhibit distinct physiological signatures and highly structured spatial distributions with mediolateral and dorsoventral positional biases. These positional distinctions constrain patterns of input from sensory and motor neurons and, as such, suggest that interneuron position is a determinant of microcircuit organization. Moreover, V1 diversity indicates that different inhibitory microcircuits exist for motor pools controlling hip, ankle, and foot muscles, revealing a variable circuit architecture for interneurons that control limb movement.

Paramutation at the maize pl1 locus is associated with RdDM activity at distal tandem repeats.

Exceptions to Mendelian inheritance often highlight novel chromosomal behaviors. The maize Pl1-Rhoades allele conferring plant pigmentation can display inheritance patterns deviating from Mendelian expectations in a behavior known as paramutation. However, the chromosome features mediating such exceptions remain unknown. Here we show that small RNA production reflecting RNA polymerase IV function within a distal downstream set of five tandem repeats is coincident with meiotically-heritable repression of the Pl1-Rhoades transcription unit. A related pl1 haplotype with three, but not one with two, repeat units also displays the trans-homolog silencing typifying paramutations. 4C interactions, CHD3a-dependent small RNA profiles, nuclease sensitivity, and polyadenylated RNA levels highlight a repeat subregion having regulatory potential. Our comparative and mutant analyses show that transcriptional repression of Pl1-Rhoades correlates with 24-nucleotide RNA production and cytosine methylation at this subregion indicating the action of a specific DNA-dependent RNA polymerase complex. These findings support a working model in which pl1 paramutation depends on trans-chromosomal RNA-directed DNA methylation operating at a discrete cis-linked and copy-number-dependent transcriptional regulatory element.

EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation.

The mechanisms that promote excitatory synapse formation and maturation have been extensively studied. However, the molecular events that limit excitatory synapse development so that synapses form at the right time and place and in the correct numbers are less well understood. We have identified a RhoA guanine nucleotide exchange factor, Ephexin5, which negatively regulates excitatory synapse development until EphrinB binding to the EphB receptor tyrosine kinase triggers Ephexin5 phosphorylation, ubiquitination, and degradation. The degradation of Ephexin5 promotes EphB-dependent excitatory synapse development and is mediated by Ube3A, a ubiquitin ligase that is mutated in the human cognitive disorder Angelman syndrome and duplicated in some forms of Autism Spectrum Disorders (ASDs). These findings suggest that aberrant EphB/Ephexin5 signaling during the development of synapses may contribute to the abnormal cognitive function that occurs in Angelman syndrome and, possibly, ASDs.

Hypoxia evokes a sequence of raphe-pontomedullary network operations for inspiratory drive amplification and gasping.

Hypoxia can trigger a sequence of breathing-related behaviors, from augmentation to apneusis to apnea and gasping. Gasping is an autoresuscitative behavior that, via large tidal volumes and altered intrathoracic pressure, can enhance coronary perfusion, carotid blood flow, and sympathetic activity, and thereby coordinate cardiac and respiratory functions. We tested the hypotheses that hypoxia-evoked gasps are amplified through a disinhibitory microcircuit within the inspiratory neuron chain, and that this drive is distributed via an efference copy mechanism. This generates coordinated gasp-like discharges concurrently in other circuits of the raphe-pontomedullary respiratory network. Data were obtained from 6 decerebrate, vagotomized, neuromuscularly-blocked, and artificially ventilated adult cats. Arterial blood pressure, phrenic nerve activity, end-tidal CO2, and other parameters were monitored. Hypoxia was produced by ventilation with a gas mixture of 5% O2 in nitrogen. Neuron spike trains were recorded at multiple pontomedullary sites simultaneously and evaluated for firing rate modulations and short-time scale correlations indicative of functional connectivity. Experimental perturbations evoked reconfiguration of raphe-pontomedullary circuits during initial augmentation, apneusis and augmented bursts, apnea, and gasping. Functional connectivity, altered firing rates, efference copy of gasp drive, and coordinated incremental blood pressure increases support a distributed brain stem network model for amplification and broadcasting of inspiratory drive during autoresuscitative gasping. Gasping begins with a reduction in inhibition by expiratory neurons and an initial loss of inspiratory drive during hypoxic apnea, and culminates in autoresuscitative efforts.

Cardiovascular event reduction among a US population eligible for semaglutide per the SELECT trial.

BACKGROUND: Our objective was to determine the number of major cardiovascular events (MACE, nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and deaths from any cause that could be prevented across varying nationwide uptake of semaglutide 2.4 mg SC weekly for the secondary prevention of cardiovascular disease. METHODS: Using a nationally representative cross-sectional study of participants in the 2017-2018 and 2019-March 2020 cycles of the National Health and Nutrition Examination Survey in the U.S. (NHANES), we estimated the number of MACE and deaths from any cause potentially prevented over a four-year period among participants meeting SELECT trial inclusion criteria. RESULTS: In a sample of n = 216 individuals (corresponding to 4,473,681 adults in the U.S. population) potentially eligible for this therapy, a total of 356,329 MACE and 232,808 all-cause mortality events were expected without semaglutide over 4 years and 35,633 MACE and 22,117 all-cause mortality events would be prevented with 50% uptake of semaglutide. CONCLUSIONS: Approximately 4.5 million adults in the U.S. are forecasted to be eligible for semaglutide 2.4mg SC weekly therapy, with substantial impact on CVD and mortality if accessible and broadly used.

Neuropsychiatric Comorbidities and Psychotropic Medication Use in Medicare Beneficiaries With Dementia by Sex and Race.

BACKGROUND: Neuropsychiatric symptoms affect the majority of dementia patients. Past studies report high rates of potentially inappropriate prescribing of psychotropic medications in this population. We investigate differences in neuropsychiatric diagnoses and psychotropic medication prescribing in a local US cohort by sex and race. METHODS: We utilize Medicare claims and prescription fill records in a cohort of 100% Medicare North and South Carolina beneficiaries ages 50 and above for the year 2017 with a dementia diagnosis. We identify dementia and quantify diagnosis of anxiety, depression and psychosis using validated coding algorithms. We search Medicare claims for antianxiety, antidepressant and antipsychotic medications to determine prescriptions filled. RESULTS: Anxiety and depression were diagnosed at higher rates in White patients; psychosis at higher rates in Black patients. (P < .001) Females were diagnosed with anxiety, depression and psychosis at higher rates than males (P < .001) and filled more antianxiety and antidepressant medications than males. (P < .001) Black and Other race patients filled more antipsychotic medications for anxiety, depression and psychosis than White patients. (P < .001) Antidepressants were prescribed at higher rates than antianxiety or antipsychotic medications across all patients and diagnoses. Of patients with no neuropsychiatric diagnosis, 11.4% were prescribed an antianxiety medication, 22.8% prescribed an antidepressant and 7.6% prescribed an antipsychotic. CONCLUSIONS: The high fill rate of antianxiety (benzodiazepine) medications in dementia patients, especially females is a concern. Patients are prescribed psychotropic medications at high rates. This practice may represent potentially inappropriate prescribing. Patient/caregiver education with innovative community outreach and care delivery models may help decrease medication use.

Paramutation and development.

Paramutation describes a heritable change of gene expression that is brought about through interactions between homologous chromosomes. Genetic analyses in plants and, more recently, in mouse indicate that genomic sequences related to transcriptional control and molecules related to small RNA biology are necessary for specific examples of paramutation. Some of the molecules identified in maize are also required for normal plant development. These observations indicate a functional relationship between the nuclear mechanisms responsible for paramutation and modes of developmental gene control.

Association between characteristics of employing healthcare facilities and healthcare worker infection rates and psychosocial experiences during the COVID-19 pandemic.

BACKGROUND: Healthcare facility characteristics, such as ownership, size, and location, have been associated with patient outcomes. However, it is not known whether the outcomes of healthcare workers are associated with the characteristics of their employing healthcare facilities, particularly during the COVID-19 pandemic. METHODS: This was an analysis of a nationwide registry of healthcare workers (the Healthcare Worker Exposure Response and Outcomes (HERO) registry). Participants were surveyed on their personal, employment, and medical characteristics, as well as our primary study outcomes of COVID-19 infection, access to personal protective equipment, and burnout. Participants from healthcare sites with at least ten respondents were included, and these sites were linked to American Hospital Association data to extract information about sites, including number of beds, teaching status, urban/rural location, and for-profit status. Generalized estimating equations were used to estimate linear regression models for the unadjusted and adjusted associations between healthcare facility characteristics and outcomes. RESULTS: A total of 8,941 healthcare workers from 97 clinical sites were included in the study. After adjustment for participant demographics, healthcare role, and medical comorbidities, facility for-profit status was associated with greater odds of COVID-19 diagnosis (aOR 1.76, 95% CI 1.02-3.03, p = .042). Micropolitan location was associated with decreased odds of COVID-19 infection after adjustment (aOR = 0.42, 95% CI 0.24, 0.71, p = .002. For-profit facility status was associated with decreased odds of burnout after adjustment (aOR = 0.53, 95% CI 0.29-0.98), p = .044). CONCLUSIONS: For-profit status of employing healthcare facilities was associated with greater odds of COVID-19 diagnosis but decreased odds of burnout after adjustment for demographics, healthcare role, and medical comorbidities. Future research to understand the relationship between facility ownership status and healthcare outcomes is needed to promote wellbeing in the healthcare workforce. TRIAL REGISTRATION: The registry was prospectively registered: ClinicalTrials.gov Identifier (trial registration number) NCT04342806, submitted April 8, 2020.

When the first try fails: re-implementation of SIMPL in a general surgery residency.

BACKGROUND: Workplace-based assessment (WBA) can facilitate evaluation of operative performance; however, implementation of WBA is sometimes unsuccessful. The American Board of Surgery Entrustable Professional Activities WBA project was launched in July 2023. Some programs will face the challenge of re-implementation of a WBA following previous failures. It is unknown what interventions are most effective for WBA re-implementation. Our goal is to identify barriers and facilitators to re-implementing SIMPL, an operative performance WBA. METHODS: The System for Improving and Measuring Procedural Learning (SIMPL) was implemented at our residency in 2018, but usage rates were low. We interviewed residents and faculty to identify barriers to usage and opportunities for improvement. Residents reported that SIMPL usage declined because of several factors, including a low faculty response rate, while some faculty reported not responding because they were unable to login to the app and because usage was not mandated. We then re-implemented SIMPL using a plan based on Kotter's Model of Change. To evaluate impact, we analyzed rates of SIMPL usage when it was first implemented, as well as before and after the date of re-implementation. RESULTS: In September 2022, we re-implemented SIMPL at our program with measures addressing the identified barriers. We found that, in the six months after re-implementation, an average of 145.8 evaluations were submitted by residents per month, compared with 47 evaluations per month at the start of the original implementation and 5.8 evaluations per month just prior to re-implementation. Faculty completed 60.6% of evaluations and dictated feedback for 59.1% of these evaluations, compared with 69.1% at implementation (44% dictated) and 43% prior to re-implementation (53% dictated). CONCLUSIONS: After identifying barriers to implementation of a WBA, we re-implemented it with significantly higher usage by faculty and residents. Future opportunities exist to implement or re-implement assessment tools within general surgery programs. These opportunities may have a significant impact in the setting of national standardization of workplace-based assessment among general surgery residencies.

Metformin Prevents Tumor Cell Growth and Invasion of Human Hormone Receptor-Positive Breast Cancer (HR+ BC) Cells via FOXA1 Inhibition.

Women with type 2 diabetes (T2D) have a higher risk of being diagnosed with breast cancer and have worse survival than non-diabetic women if they do develop breast cancer. However, more research is needed to elucidate the biological underpinnings of these relationships. Here, we found that forkhead box A1 (FOXA1), a forkhead family transcription factor, and metformin (1,1-dimethylbiguanide hydrochloride), a medication used to treat T2D, may impact hormone-receptor-positive (HR+) breast cancer (BC) tumor cell growth and metastasis. Indeed, fourteen diabetes-associated genes are highly expressed in only three HR+ breast cancer cell lines but not the other subtypes utilizing a 53,805 gene database obtained from NCBI GEO. Among the diabetes-related genes, FOXA1, MTA3, PAK4, FGFR3, and KIF22 were highly expressed in HR+ breast cancer from 4032 breast cancer patient tissue samples using the Breast Cancer Gene Expression Omnibus. Notably, elevated FOXA1 expression correlated with poorer overall survival in patients with estrogen-receptor-positive/progesterone-receptor-positive (ER+/PR+) breast cancer. Furthermore, experiments demonstrated that loss of the FOXA1 gene inhibited tumor proliferation and invasion in vitro using MCF-7 and T47D HR+ breast cancer cell lines. Metformin, an anti-diabetic medication, significantly suppressed tumor cell growth in MCF-7 cells. Additionally, either metformin treatment or FOXA1 gene deletion enhanced tamoxifen-induced tumor growth inhibition in HR+ breast cancer cell lines within an ex vivo three-dimensional (3D) organoid model. Therefore, the diabetes-related medicine metformin and FOXA1 gene inhibition might be a new treatment for patients with HR+ breast cancer when combined with tamoxifen, an endocrine therapy.

Frailty is a predictor of immediate postoperative complications following surgical management of knee dislocations.

PURPOSE: To assess the utility of frailty in predicting outcomes following surgical intervention for KDs. METHODS: The NIS database was queried for non-congenital knee dislocations from 2015 to 2019 that underwent ligament repair or surgical reduction. Patients were assigned frailty scores using the mFI-11, and outcomes were compared. Multivariate regression and ROC curve analysis were used to assess the independent association of obesity, frailty, VI, and age with adverse outcomes. RESULTS: A total of 3797 patients who underwent surgical management were included. Frailty was associated with extended LOS (OR 1.353, 95% CI 1.212-1.510, p < 0.001), adverse discharge (OR 1.716, 95% CI 1.515-1.946, p < 0.001), and complications (OR 1.449, 95% CI 1.352-1.553, p < 0.001). Severely frailty was associated with extended LOS (OR 1.838, 95% CI 1.611-2.097, p < 0.001), adverse discharge (OR 2.756, 95% CI 2.394-3.171, p < 0.001), and complications (OR 1.603, 95% CI 1.453-1.768, p < 0.001). Additionally, VI was a risk factor for extended LOS (OR 7.647 (6.442-9.076) p < 0.001), complications (OR 2.065 (1.810-2.341) p < 0.001), and adverse discharge (OR 1.825 (1.606-2.075), p < 0.001). Obesity was a risk factor for extended LOS (OR 1.599 (1.470-1.739), p < 0.001) and complications (OR 1.235 (1.108-1.377), p < 0.001). AUC analysis showed that frailty was the most accurate predictor of all outcomes when compared to VI, obesity, and age. CONCLUSIONS: Frailty is superior to age and obesity, and comparable to VI, at predicting adverse outcomes following surgical management of KDs. These findings suggest that frailty assessment might play a role in risk stratification and preoperative planning for KD patients that require surgical intervention.

Association Between Hospital-Documented Atrial Fibrillation and Central Retinal Artery Occlusion.

BACKGROUND: Carotid stenosis is thought to be the primary risk factor for central retinal artery occlusion (CRAO); however, it is not known whether atrial fibrillation (AF)-a cardiac arrhythmia that underlies over 25% of cerebral ischemic strokes-predisposes patients to CRAO. METHODS: A retrospective, observational, cohort study was performed using data from the State Inpatient Databases and State Emergency Department Databases from New York (2006-2015), California (2003-2011), and Florida (2005-2015) to determine the association between AF and CRAO. The primary exposure was hospital-documented AF. The primary end point was hospital-documented CRAO, defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification, code 362.31 in the primary diagnosis position. Cause-specific hazard models were used to model CRAO-free survival among patients according to hospital-documented AF status. RESULTS: Of 39 834 885 patients included in the study, 2 723 842 (median age, 72.7 years; 48.5% women) had AF documented during the exposure window. The median follow-up duration was 6 years and 1 month. Patients with AF were older, more likely to be of non-Hispanic White race/ethnicity, and had a higher burden of cardiovascular comorbidities compared with patients without AF. The cumulative incidence of CRAO determined prospectively after exclusions was 8.69 per 100 000 at risk in those with AF and 2.39 per 100 000 at risk in those without AF over the study period. Before adjustment, AF was associated with higher risk of CRAO (hazard ratio, 2.55 [95% CI, 2.15-3.03]). However, after adjustment for demographics, state, and cardiovascular comorbidities, there was an inverse association between AF and risk of CRAO (adjusted hazard ratio, 0.72 [95% CI, 0.60-0.87]). These findings were robust in our prespecified sensitivity analyses. By contrast, positive control outcomes of embolic and ischemic stroke showed an expected strong relationship between AF and risk of stroke. CONCLUSIONS: We found an inverse association between AF and CRAO in a large, representative study of hospitalized patients; however, this cohort did not ascertain AF or CRAO occurring outside of hospital or emergency department settings.

Public reporting of black participation in anti-hypertensive drug clinical trials.

BACKGROUND: Non-Hispanic Black people in the United States have the highest prevalence of essential hypertension. Unfortunately, clinical trials often underrepresent Black patients. We aim to understand whether trial sponsorship type is associated with representation of Black participants in anti-hypertensive drug clinical trials. Then, we contextualize our findings amongst current efforts to improve diversity in clinical research populations. METHODS: We searched ClinicalTrials.gov in May 2022 for antihypertensive drug trials. Of n = 408 trials in our initial search, n = 97 (23.77%) met inclusion criteria and were stratified by sponsorship type (industry vs non-industry). Standardized tests of difference were employed to compare characteristics of these trials, and linear regression was used to model change over time. RESULTS: Of 97 trials reporting results from 2010 to 2020, there were minimal differences in the percent of Black patients enrolled in anti-hypertensive clinical trials by sponsorship type. Both industry and non-industry sponsored studies had high rates of non-reporting, with slightly more non-reporting for industry (73.2%) vs non-industry (66.67%) studies. Industry funded studies reported results to ClinicalTrials.gov within 23.3 ± 15.0 months from completing studies, while non-industry funded trials reported within 18.9 ± 10.8 months. CONCLUSIONS: Despite Black Americans carrying the highest burden of disease for essential hypertension, they are underrepresented in anti-hypertension clinical trials and their overall participation has decreased between 2010 and 2020. In addition, there is major underreporting of trial participant race. We implore researchers and funders to establish clear, meaningful targets for anti-hypertensive drug trial diversity, and improve transparency in reporting of study characteristics.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Association between macrophage-like cell density and ischemia metrics in diabetic eyes.

We previously showed that macrophage-like cells (MLCs) are increased in eyes with advanced diabetic retinopathy (DR). Here, we hypothesized that MLC density was correlated with ischemia using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography (UWF-FA). Treatment-naïve diabetic eyes were prospectively imaged with repeated OCTA (average 5.3 scans per eye) and UWF-FA imaging. OCTA images were registered and averaged to generate a superficial capillary plexus (SCP), deep capillary plexus (DCP), and MLC slab. We calculated geometric perfusion deficit (GPD), vessel length density, and vessel density for the SCP and DCP. MLC density was quantified by two masked graders and averaged. Ischemia on UWF-FA was measured to generate a non-perfusion area (NPA) and index (NPI). Since MLC density was non-parametrically distributed, MLC density was correlated with ischemia metrics using Spearman correlations. Forty-five treatment-naïve eyes of 45 patients (59 ± 12 years of age; 56% female) were imaged. We included 6 eyes with no DR, 7 eyes with mild non-proliferative DR (NPDR), 22 moderate NPDR, 4 severe NPDR, and 6 PDR eyes. MLC density between graders was highly correlated (r = 0.9592, p < 0.0001). MLC density was correlated with DCP GPD (r = 0.296, p = 0.049), but no other OCTA ischemia metrics. MLC density was also correlated with UWF-FA NPA (r = 0.330, p = 0.035) and NPI (r = 0.332, p = 0.034). MLC density was correlated with total ischemia on UWF-FA and local DCP GPD. Since both UWF-FA and DCP non-perfusion are associated with higher risk for DR progression, MLC density could be another potential biomarker for DR progression.

Paramutation and related phenomena in diverse species.

Paramutation describes a process that results in heritable epigenetic changes of gene regulation and trans-homologue interactions. Recent discoveries in model organisms have highlighted roles for the respective nuclear systems that regulate transposons via small RNA molecules both for paramutation and for defining transgenerational inheritance. Differences between plants and animals may influence specific transmission behaviours but the involvement of small RNA-based mechanisms identifies a unifying eukaryotic theme. These mechanisms that specify heritable epigenetic information represent genetic systems adjunct to DNA sequences that contribute to phenotypic diversity.

Dementia and Parkinson's disease diagnoses in electronic health records vs. Medicare claims data: a study of 101,980 linked patients.

BACKGROUND: Medicare claims and electronic health record data are both commonly used for research and clinical practice improvement; however, it is not known how concordant diagnoses of neurodegenerative diseases (NDD, comprising dementia and Parkinson's disease) are in these data types. Therefore, our objective was to determine the sensitivity and specificity of neurodegenerative disease (NDD) diagnoses contained in structured electronic health record (EHR) data compared to Medicare claims data. METHODS: This was a retrospective cohort study of 101,980 unique patients seen at a large North Carolina health system between 2013-2017, which were linked to 100% North and South Carolina Medicare claims data, to evaluate the accuracy of diagnoses of neurodegenerative diseases in EHRs compared to Medicare claims data. Patients age > 50 who were enrolled in fee-for-service Medicare were included in the study. Patients were classified as having or not having NDD based on the presence of validated ICD-CM-9 or ICD-CM-10 codes associated with NDD or claims for prescription drugs used to treat NDD. EHR diagnoses were compared to Medicare claims diagnoses. RESULTS: The specificity of any EHR diagnosis of NDD was 99.0%; sensitivity was 61.3%. Positive predictive value and negative predictive value were 90.8% and 94.1% respectively. Specificity of an EHR diagnosis of dementia was 99.0%, and sensitivity was 56.1%. Specificity of an EHR diagnosis of PD was 99.7%, while sensitivity was 76.1%. CONCLUSIONS: More research is needed to investigate under-documentation of NDD in electronic health records relative to Medicare claims data, which has major implications for clinical practice (particularly patient safety) and research using real-world data.

Robotic Optical Coherence Tomography Retinal Imaging for Emergency Department Patients: A Pilot Study for Emergency Physicians' Diagnostic Performance.

STUDY OBJECTIVE: To evaluate the diagnostic performance of emergency physicians' interpretation of robotically acquired retinal optical coherence tomography images for detecting posterior eye abnormalities in patients seen in the emergency department (ED). METHODS: Adult patients presenting to Duke University Hospital emergency department from November 2020 through October 2021 with acute visual changes, headache, or focal neurologic deficit(s) who received an ophthalmology consultation were enrolled in this pilot study. Emergency physicians provided standard clinical care, including direct ophthalmoscopy, at their discretion. Retinal optical coherence tomography images of these patients were obtained with a robotic, semi-autonomous optical coherence tomography system. We compared the detection of abnormalities in optical coherence tomography images by emergency physicians with a reference standard, a combination of ophthalmology consultation diagnosis and retina specialist optical coherence tomography review. RESULTS: Nine emergency physicians reviewed the optical coherence tomography images of 72 eyes from 38 patients. Based on the reference standard, 33 (46%) eyes were normal, 16 (22%) had at least 1 urgent/emergency abnormality, and the remaining 23 (32%) had at least 1 nonurgent abnormality. Emergency physicians' optical coherence tomography interpretation had 69% (95% confidence interval [CI], 49% to 89%) sensitivity for any abnormality, 100% (95% CI, 79% to 100%) sensitivity for urgent/emergency abnormalities, 48% (95% CI, 28% to 68%) sensitivity for nonurgent abnormalities, and 64% (95% CI, 44% to 84%) overall specificity. In contrast, emergency physicians providing standard clinical care did not detect any abnormality with direct ophthalmoscopy. CONCLUSION: Robotic, semi-autonomous optical coherence tomography enabled ocular imaging of emergency department patients with a broad range of posterior eye abnormalities. In addition, emergency provider optical coherence tomography interpretation was more sensitive than direct ophthalmoscopy for any abnormalities, urgent/emergency abnormalities, and nonurgent abnormalities in this pilot study with a small sample of patients and emergency physicians.

Neighborhood socioeconomic deprivation, healthcare access, and 30-day mortality and readmission after sepsis or critical illness: findings from a nationwide study.

BACKGROUND: To determine if neighborhood socioeconomic deprivation independently predicts 30-day mortality and readmission for patients with sepsis or critical illness after adjusting for individual poverty, demographics, comorbidity burden, access to healthcare, and characteristics of treating healthcare facilities. METHODS: We performed a nationwide study of United States Medicare beneficiaries from 2017 to 2019. We identified hospitalized patients with severe sepsis and patients requiring prolonged mechanical ventilation, tracheostomy, or extracorporeal membrane oxygenation (ECMO) through Diagnosis Related Groups (DRGs). We estimated the association between neighborhood socioeconomic deprivation, measured by the Area Deprivation Index (ADI), and 30-day mortality and unplanned readmission using logistic regression models with restricted cubic splines. We sequentially adjusted for demographics, individual poverty, and medical comorbidities, access to healthcare services; and characteristics of treating healthcare facilities. RESULTS: A total of 1,526,405 admissions were included in the mortality analysis and 1,354,548 were included in the readmission analysis. After full adjustment, 30-day mortality for patients was higher for those from most-deprived neighborhoods (ADI 100) compared to least deprived neighborhoods (ADI 1) for patients with severe sepsis (OR 1.35 95% [CI 1.29-1.42]) or with prolonged mechanical ventilation with or without sepsis (OR 1.42 [95% CI 1.31, 1.54]). This association was linear and dose dependent. However, neighborhood socioeconomic deprivation was not associated with 30-day unplanned readmission for patients with severe sepsis and was inversely associated with readmission for patients requiring prolonged mechanical ventilation with or without sepsis. CONCLUSIONS: A strong association between neighborhood socioeconomic deprivation and 30-day mortality for critically ill patients is not explained by differences in individual poverty, demographics, measured baseline medical risk, access to healthcare resources, or characteristics of treating hospitals.