Housing instability increases for stimulant-involved overdose deaths after linking surveillance data to electronic health records in Kentucky.

BACKGROUND: According to the U.S. Centers for Disease Control and Prevention, approximately 10.2 % of fatal overdoses in 2022 were among people experiencing homelessness or housing instability. In the United States, the majority of all drug overdoses now involve stimulants. METHODS: We linked stimulant-involved fatal overdose records occurring between 2017 and 2021 from Kentucky's Drug Overdose Fatality Surveillance System to the electronic health records (EHR) of the state's largest safety-net hospital network. We used State Unintentional Drug Overdose Reporting System (SUDORS) definitions of homelessness or housing instability to establish baseline estimates before linking decedents to medical records. After linkage, we augmented SUDORS data with structured administrative billing codes, semi-structured address data, and unstructured clinical notes identifying homelessness from the EHR. RESULTS: There were 313 individuals with stimulant-involved fatal overdoses linked to at least one medical encounter in the EHR (2017-2021). Thirty-three individuals (10.5 %) were identified as having unstable housing according to SUDORS. After linkage, 130 individuals (41.5 %) had evidence of housing instability. For this period, these 313 individuals represent 8.0 % of stimulant-involved overdoses in KY or 38.5 % of stimulant-involved overdoses from residents of the primary and secondary catchment area of our healthcare network. CONCLUSIONS: The single-site increase in observed housing instability in stimulant-involved fatal overdoses suggests that increased data linkage between state medicolegal death investigation system and EHRs would significantly improve the public health surveillance of overdoses.

Health equity in COVID-19 testing among patients of a large national pharmacy chain.

Background: Several social determinants of health and other structural factors drive racial and ethnic disparities in COVID-19 risk, morbidity, and mortality. Public-private collaborations with community pharmacies have been successful in expanding access to COVID-19 testing and reaching historically underserved communities. The objectives of this study were to describe individuals who sought testing for COVID-19 at a national community pharmacy chain and to understand potential racial and ethnic inequities in testing access, positivity, and infection with emerging variants of concern. Methods: We conducted a cross-sectional study of individuals aged ≥18 who were tested for COVID-19 (SARS-CoV-2) at a Walgreens pharmacy or Walgreen-affiliated mass testing site between May 1, 2021 and February 28, 2022. Positivity was defined as the proportion of positive tests among all administered tests. A geographically balanced random subset of positive tests underwent whole genome sequencing to identify specific viral variants (alpha, delta, and omicron). Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) to compare the likelihood of testing positive and testing positive with an emerging variant of concern across race and ethnicity groups. Results: A total of 18,576,360 tests were analyzed (16.0% tests were positive for COVID-19; 59.5% of tests were from White individuals and 13.1% were from Black individuals). American Indian or Alaska Native (OR = 1.12; 95%CI = 1.10-1.13), Hispanic or Latino (1.20; 95%CI = 1.120, 1.21), and Black (1.12; 95%CI = 1.12, 1.13) individuals were more likely to test positive for COVID-19 compared to White individuals. Non-White individuals were also more likely to test positive for emerging variants of concern (e.g., Black individuals were 3.34 (95%CI = 3.14-3.56) times more likely to test positive for omicron compared to White individuals during the transition period from delta to omicron). Discussion: Using a national database of testing data, we found racial and ethnic differences in the likelihood of testing positive for COVID-19 and testing positive for emerging viral strains. These results demonstrate the feasibility of public-private collaborations with local pharmacies and pharmacy chains to support pandemic response and reach harder to reach populations with important health services.

Lessons Learned From Developing Dashboards to Support Decision-Making for Community Opioid Response by Community Stakeholders: Mixed Methods and Multisite Study.

BACKGROUND: Data dashboards are published tools that present visualizations; they are increasingly used to display data about behavioral health, social determinants of health, and chronic and infectious disease risks to inform or support public health endeavors. Dashboards can be an evidence-based approach used by communities to influence decision-making in health care for specific populations. Despite widespread use, evidence on how to best design and use dashboards in the public health realm is limited. There is also a notable dearth of studies that examine and document the complexity and heterogeneity of dashboards in community settings. OBJECTIVE: Community stakeholders engaged in the community response to the opioid overdose crisis could benefit from the use of data dashboards for decision-making. As part of the Communities That HEAL (CTH) intervention, community data dashboards were created for stakeholders to support decision-making. We assessed stakeholders' perceptions of the usability and use of the CTH dashboards for decision-making. METHODS: We conducted a mixed methods assessment between June and July 2021 on the use of CTH dashboards. We administered the System Usability Scale (SUS) and conducted semistructured group interviews with users in 33 communities across 4 states of the United States. The SUS comprises 10 five-point Likert-scale questions measuring usability, each scored from 0 to 4. The interview guides were informed by the technology adoption model (TAM) and focused on perceived usefulness, perceived ease of use, intention to use, and contextual factors. RESULTS: Overall, 62 users of the CTH dashboards completed the SUS and interviews. SUS scores (grand mean 73, SD 4.6) indicated that CTH dashboards were within the acceptable range for usability. From the qualitative interview data, we inductively created subthemes within the 4 dimensions of the TAM to contextualize stakeholders' perceptions of the dashboard's usefulness and ease of use, their intention to use, and contextual factors. These data also highlighted gaps in knowledge, design, and use, which could help focus efforts to improve the use and comprehension of dashboards by stakeholders. CONCLUSIONS: We present a set of prioritized gaps identified by our national group and list a set of lessons learned for improved data dashboard design and use for community stakeholders. Findings from our novel application of both the SUS and TAM provide insights and highlight important gaps and lessons learned to inform the design of data dashboards for use by decision-making community stakeholders. TRIAL REGISTRATION: ClinicalTrials.gov NCT04111939; https://clinicaltrials.gov/study/NCT04111939.

A Case Demonstration of the Open Health Natural Language Processing Toolkit From the National COVID-19 Cohort Collaborative and the Researching COVID to Enhance Recovery Programs for a Natural Language Processing System for COVID-19 or Postacute Sequelae of SARS CoV-2 Infection: Algorithm Development and Validation.

BACKGROUND: A wealth of clinically relevant information is only obtainable within unstructured clinical narratives, leading to great interest in clinical natural language processing (NLP). While a multitude of approaches to NLP exist, current algorithm development approaches have limitations that can slow the development process. These limitations are exacerbated when the task is emergent, as is the case currently for NLP extraction of signs and symptoms of COVID-19 and postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: This study aims to highlight the current limitations of existing NLP algorithm development approaches that are exacerbated by NLP tasks surrounding emergent clinical concepts and to illustrate our approach to addressing these issues through the use case of developing an NLP system for the signs and symptoms of COVID-19 and PASC. METHODS: We used 2 preexisting studies on PASC as a baseline to determine a set of concepts that should be extracted by NLP. This concept list was then used in conjunction with the Unified Medical Language System to autonomously generate an expanded lexicon to weakly annotate a training set, which was then reviewed by a human expert to generate a fine-tuned NLP algorithm. The annotations from a fully human-annotated test set were then compared with NLP results from the fine-tuned algorithm. The NLP algorithm was then deployed to 10 additional sites that were also running our NLP infrastructure. Of these 10 sites, 5 were used to conduct a federated evaluation of the NLP algorithm. RESULTS: An NLP algorithm consisting of 12,234 unique normalized text strings corresponding to 2366 unique concepts was developed to extract COVID-19 or PASC signs and symptoms. An unweighted mean dictionary coverage of 77.8% was found for the 5 sites. CONCLUSIONS: The evolutionary and time-critical nature of the PASC NLP task significantly complicates existing approaches to NLP algorithm development. In this work, we present a hybrid approach using the Open Health Natural Language Processing Toolkit aimed at addressing these needs with a dictionary-based weak labeling step that minimizes the need for additional expert annotation while still preserving the fine-tuning capabilities of expert involvement.

Trends in Atherosclerotic Cardiovascular Disease and lipid management. A population-level observational cohort study in Wales.

AIMS: European clinical guidelines recommend that patients with atherosclerotic cardiovascular disease (ASCVD), including ischaemic heart disease (IHD), stroke and peripheral arterial disease (PAD), are prescribed lipid lowering treatment (LLT) and treated to target low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to document trends in ASCVD including treatment, monitoring, and achievement of target LDL-C. METHOD: A retrospective observational population study using linked health-care data (2010-22). RESULTS: Over the study period the number of patients with ASCVD increased from 181,153 to 207,747 (8882 to 9398 per 100,000). The proportion of patients prescribed LLT decreased from 75.3% in 2010 to 67.1% in 2022; high-intensity statin therapy increased from 9.4% to 25.2% and non-high-intensity statin therapy decreased from 59.6% to 38.2%. The prescribing of high-intensity statin therapy was consistently higher amongst patients with IHD (10.9% in 2010 increasing to 28.0% in 2022) than in patients with stroke (4.7% to 21.6%) or PAD (3.9% to 10.6%).The proportion of cases with documented LDL-C decreased from 58.0% in 2010 to 49.3% in 2022. Of those with documented LDL-C in 2022, 44.0% achieved LDL-C <1.8 mmol/L, including 45.2% of those with IHD, 42.0% of those with stroke and only 32.8% of those with PAD. CONCLUSION: Prescribing of LLT, including HI-statin therapy, documentation of LDL-C and achievement of target LDL-C levels was relatively low, especially in PAD patients. Although target achievement in "tested patients" increased over time, the proportion of patients undergoing lipid testing declined. More rigorous lipid management requires prioritisation, especially for PAD and stroke patients.

We analysed trends in the presentation of atherosclerotic cardiovascular disease and lipid management in a population between 2010 to 2022 The number of patients with atherosclerotic cardiovascular disease increased by 14% but the proportion receiving lipid lowering therapy decreased.Patients with ischaemic heart disease were more effectively managed than patients with stroke and patients with peripheral arterial disease were the least effectively managed.

Antipsychotic Discontinuation and New Trazodone Use in Ontario Nursing Homes: Evidence of Medication Substitution.

OBJECTIVES: An unintended consequence of efforts to reduce antipsychotic medications in nursing homes is the increase in use of other psychotropic medications; however, evidence of substitution remains limited. Our objective was to measure individual-level prescribing patterns consistent with substitution of trazodone for antipsychotics. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Residents of Ontario nursing homes aged 66-105 years with an admission assessment between April 1, 2010, and March 31, 2019, who were receiving an antipsychotic and had no antidepressant medication use at admission to the nursing home. METHODS: We used linked health administrative data to examine changes in medication use over three quarterly assessments following admission. Antipsychotic and trazodone use were measured at each assessment. The rate of trazodone initiation was compared between residents no longer dispensed an antipsychotic (discontinued) and those with an ongoing antipsychotic (continued) using discrete time survival analysis, controlling for baseline resident characteristics. RESULTS: We identified 13,306 residents dispensed an antipsychotic with no antidepressant use at admission (mean age 84 years, 61.5% women, 82.8% with dementia). As of the first quarterly assessment, nearly 20% of residents no longer received an antipsychotic and 9% received a new trazodone medication. Over time, residents who discontinued antipsychotics had a rate of trazodone initiation that was 82% higher compared to residents who continued (adjusted hazard ratio 1.82, 95% CI 1.66-2.00). CONCLUSIONS AND IMPLICATIONS: Residents admitted to a nursing home with antipsychotic use had a higher rate of trazodone initiation if they discontinued (vs continued) an antipsychotic. These findings suggest antipsychotic substitution with trazodone after entering a nursing home.

Interactions and pattern formation in a macroscopic magnetocapillary SALR system of mermaid cereal.

When particles are deposited at a fluid interface they tend to aggregate by capillary attraction to minimize the overall potential energy of the system. In this work, we embed floating millimetric disks with permanent magnets to introduce a competing repulsion effect and study their pattern formation in equilibrium. The pairwise energy landscape of two disks is described by a short-range attraction and long-range repulsion (SALR) interaction potential, previously documented in a number of microscopic condensed matter systems. Such competing interactions enable a variety of pairwise equilibrium states, including the possibility of a local minimum energy corresponding to a finite disk spacing. Two-dimensional (2D) experiments and simulations in confined geometries demonstrate that as the areal packing fraction is increased, the dilute repulsion-dominated lattice state becomes unstable to the spontaneous formation of localized clusters, which eventually merge into a system-spanning striped pattern. Finally, we demonstrate that the equilibrium pattern can be externally manipulated by the application of a supplemental vertical magnetic force that remotely enhances the effective capillary attraction.

COVID-19 Vaccines: Moderna And Pfizer-BioNTech Use Varied By Urban, Rural Counties.

We investigated county-level variation in mRNA COVID-19 vaccine use among Medicare beneficiaries throughout the United States. There was greater use of Pfizer-BioNTech vaccines than Moderna vaccines in urban areas for first and booster doses.

Geospatial Imprecision With Constraints for Precision Public Health: Algorithm Development and Validation.

BACKGROUND: Location and environmental social determinants of health are increasingly important factors in both an individual's health and the monitoring of community-level public health issues. OBJECTIVE: We aimed to measure the extent to which location obfuscation techniques, designed to protect an individual's privacy, can unintentionally shift geographical coordinates into neighborhoods with significantly different socioeconomic demographics, which limits the precision of findings for public health stakeholders. METHODS: Point obfuscation techniques intentionally blur geographic coordinates to conceal the original location. The pinwheel obfuscation method is an existing technique in which a point is moved along a pinwheel-like path given a randomly chosen angle and a maximum radius; we evaluate the impact of this technique using 2 data sets by comparing the demographics of the original point and the resulting shifted point by cross-referencing data from the United States Census Bureau. RESULTS: Using poverty measures showed that points from regions of low poverty may be shifted to regions of high poverty; similarly, points in regions with high poverty may be shifted into regions of low poverty. We varied the maximum allowable obfuscation radius; the mean difference in poverty rate before and after obfuscation ranged from 6.5% to 11.7%. Additionally, obfuscation inadvertently caused false hot spots for deaths by suicide in Cook County, Illinois. CONCLUSIONS: Privacy concerns require patient locations to be imprecise to protect against risk of identification; precision public health requires accuracy. We propose a modified obfuscation technique that is constrained to generate a new point within a specified census-designated region to preserve both privacy and analytical accuracy by avoiding demographic shifts.

Altered mechanisms of adaptation in social anxiety: differences in adapting to positive versus negative emotional faces.

Social anxiety is characterised by fear of negative evaluation and negative perceptual biases; however, the cognitive mechanisms underlying these negative biases are not well understood. We investigated a possible mechanism which could maintain negative biases: altered adaptation to emotional faces. Heightened sensitivity to negative emotions could result from weakened adaptation to negative emotions, strengthened adaptation to positive emotions, or both mechanisms. We measured adaptation from repeated exposure to either positive or negative emotional faces, in individuals high versus low in social anxiety. We quantified adaptation strength by calculating the point of subjective equality (PSE) before and after adaptation for each participant. We hypothesised: (1) weaker adaptation to angry vs happy faces in individuals high in social anxiety, (2) no difference in adaptation to angry vs happy faces in individuals low in social anxiety, and (3) no difference in adaptation to sad vs happy faces in individuals high in social anxiety. Our results revealed a weaker adaptation to angry compared to happy faces in individuals high in social anxiety (Experiment 1), with no such difference in individuals low in social anxiety (Experiment 1), and no difference in adaptation strength to sad vs happy faces in individuals high in social anxiety (Experiment 2).

Adherence to the Atrial fibrillation Better Care pathway and the risk of adverse health outcomes in older care home residents with atrial fibrillation: a retrospective data linkage study 2003-18.

BACKGROUND: The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown. OBJECTIVE: To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents. METHODS: A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence. RESULTS: From 14,493 residents (median [interquartile range] age 87.0 [82.6-91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97-1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50-0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06-2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined. CONCLUSION: An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended.

Impact of the Communities That HEAL Intervention on Buprenorphine-Waivered Practitioners and Buprenorphine Prescribing: A Prespecified Secondary Analysis of the HCS Randomized Clinical Trial.

Importance: Buprenorphine significantly reduces opioid-related overdose mortality. From 2002 to 2022, the Drug Addiction Treatment Act of 2000 (DATA 2000) required qualified practitioners to receive a waiver from the Drug Enforcement Agency to prescribe buprenorphine for treatment of opioid use disorder. During this period, waiver uptake among practitioners was modest; subsequent changes need to be examined. Objective: To determine whether the Communities That HEAL (CTH) intervention increased the rate of practitioners with DATA 2000 waivers and buprenorphine prescribing. Design, Setting, and Participants: This prespecified secondary analysis of the HEALing Communities Study, a multisite, 2-arm, parallel, community-level, cluster randomized, open, wait-list-controlled comparison clinical trial was designed to assess the effectiveness of the CTH intervention and was conducted between January 1, 2020, to December 31, 2023, in 67 communities in Kentucky, Massachusetts, New York, and Ohio, accounting for approximately 8.2 million adults. The participants in this trial were communities consisting of counties (n = 48) and municipalities (n = 19). Trial arm randomization was conducted using a covariate constrained randomization procedure stratified by state. Each state was balanced by community characteristics including urban/rural classification, fatal opioid overdose rate, and community population. Thirty-four communities were randomized to the intervention and 33 to wait-list control arms. Data analysis was conducted between March 20 and September 29, 2023, with a focus on the comparison period from July 1, 2021, to June 30, 2022. Intervention: Waiver trainings and other educational trainings were offered or supported by the HEALing Communities Study research sites in each state to help build practitioner capacity. Main Outcomes and Measures: The rate of practitioners with a DATA 2000 waiver (overall, and stratified by 30-, 100-, and 275-patient limits) per 100 000 adult residents aged 18 years or older during July 1, 2021, to June 30, 2022, were compared between the intervention and wait-list control communities. The rate of buprenorphine prescribing among those waivered practitioners was also compared between the intervention and wait-list control communities. Intention-to-treat and per-protocol analyses were performed. Results: A total of 8 166 963 individuals aged 18 years or older were residents of the 67 communities studied. There was no evidence of an effect of the CTH intervention on the adjusted rate of practitioners with a DATA 2000 waiver (adjusted relative rate [ARR], 1.04; 95% CI, 0.94-1.14) or the adjusted rate of practitioners with a DATA 2000 waiver who actively prescribed buprenorphine (ARR, 0.97; 95% CI, 0.86-1.10). Conclusions and Relevance: In this randomized clinical trial, the CTH intervention was not associated with increases in the rate of practitioners with a DATA 2000 waiver or buprenorphine prescribing among those waivered practitioners. Supporting practitioners to prescribe buprenorphine remains a critical yet challenging step in the continuum of care to treat opioid use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT04111939.

COVID-19 and Influenza Vaccine Coadministration Among Older U.S. Adults.

INTRODUCTION: Coadministering COVID-19 and influenza vaccines is recommended by public health authorities and intended to improve uptake and convenience; however, the extent of vaccine coadministration is largely unknown. Investigations into COVID-19 and influenza vaccine coadministration are needed to describe compliance with newer recommendations and to identify potential gaps in the implementation of coadministration. METHODS: A descriptive, repeated cross-sectional study between September 1, 2021 to November 30, 2021 (Period 1) and September 1, 2022 to November 30, 2022 (Period 2) was conducted. This study included community-dwelling Medicare beneficiaries ≥ 66 years who received an mRNA COVID-19 booster vaccine in Periods 1 and 2. The outcome was an influenza vaccine administered on the same day as the COVID-19 vaccine. Adjusted ORs and 99% CIs were estimated using logistic regression to describe the association between beneficiaries' characteristics and vaccine coadministration. Statistical analysis was performed in 2023. RESULTS: Among beneficiaries who received a COVID-19 vaccine, 78.8% in Period 1 (N=6,292,777) and 89.1% in Period 2 (N=4,757,501), received an influenza vaccine at some point during the study period (i.e., before, after, or on the same day as their COVID-19 vaccine), though rates were lower in non-White and rural individuals. Vaccine coadministration increased from 11.1% to 36.5% between periods. Beneficiaries with dementia (aORPeriod 2=1.31; 99%CI=1.29-1.32) and in rural counties (aORPeriod 2=1.19; 99%CI=1.17-1.20) were more likely to receive coadministered vaccines, while those with cancer (aORPeriod 2=0.90; 99%CI=0.89-0.91) were less likely. CONCLUSIONS: Among Medicare beneficiaries vaccinated against COVID-19, influenza vaccination was high, but coadministration of the 2 vaccines was low. Future work should explore which factors explain variation in the decision to receive coadministered vaccines.

Assessing the prediction of arterial CO2 from end tidal CO2 in adult blunt trauma patients.

BACKGROUND: The control of PaCO2 in ventilated patients is known to be of particular importance in the management and prognosis of trauma patients. Although EtCO2 is often used as a continuous, non-invasive, surrogate marker for PaCO2 in ventilated trauma patients in the emergency department (ED), previous studies suggest a poor correlation in this cohort. However, previous data has predominantly been collected retrospectively, raising the possibility that the elapsed time between PaCO2 sampling and EtCO2 recording may contribute to the poor correlation. As such this study aimed to analyse the correlation of PaCO2 to EtCO2 in the ventilated blunt trauma patient presenting to the ED through contemporaneous sampling. METHODS: This study was conducted as a prospective observational study analysing the near simultaneous recording of EtCO2 and Arterial Blood Gas sampling of ventilated adult trauma patients in the ED of a Level 1 trauma centre over a 12-month period. Data was analysed using linear regression and subgroup analysis by Injury Severity Score (ISS) and Abbreviated Injury Score (AIS) of the Chest. RESULTS: Linear regression of EtCO2 vs PaCO2 demonstrated a moderate correlation with r = 0.54 (p < 0.01, n = 51, 95 % CI 0.31-0.71). Subgroup analysis by ISS, revealed a stronger correlation in those with minor ISS (0-11) (r = 0.76, p < 0.01, n = 13, 95 % CI 0.36-0.92) compared to those more severely injured patients (ISS > 15) (r = 0.44, P < 0.01, n = 38, 95 % CI 0.14-0.67). Analysis by AIS Chest demonstrated similar correlation between patients without chest injuries (AIS 0) (r = 0.55, n = 29, p < 0.01, 95 % CI 0.23-0.76) and those with an AIS >1 (r = 0.51, n = 22, p = 0.02, 95 % CI 0.11-0.77). In patients with traumatic head injuries who had an EtCO2 between 30 and 39 mmHg, only 57 % had a measured PaCO2 within 5 mmHg. CONCLUSIONS: As patients transition from minor to seriously injured, a decreasing strength of PaCO2 to EtCO2 correlation is observed, decreasing the reliability of EtCO2 as a surrogate marker of PaCO2 in this patient group. This inconsistency cannot be accounted for by the presence of chest injuries and worryingly is frequently seen in those with traumatic brain injuries.

Diverse African genomes reveal selection on ancient modern human introgressions in Neanderthals.

Comparisons of Neanderthal genomes to anatomically modern human (AMH) genomes show a history of Neanderthal-to-AMH introgression stemming from interbreeding after the migration of AMHs from Africa to Eurasia. All non-sub-Saharan African AMHs have genomic regions genetically similar to Neanderthals that descend from this introgression. Regions of the genome with Neanderthal similarities have also been identified in sub-Saharan African populations, but their origins have been unclear. To better understand how these regions are distributed across sub-Saharan Africa, the source of their origin, and what their distribution within the genome tells us about early AMH and Neanderthal evolution, we analyzed a dataset of high-coverage, whole-genome sequences from 180 individuals from 12 diverse sub-Saharan African populations. In sub-Saharan African populations with non-sub-Saharan African ancestry, as much as 1% of their genomes can be attributed to Neanderthal sequence introduced by recent migration, and subsequent admixture, of AMH populations originating from the Levant and North Africa. However, most Neanderthal homologous regions in sub-Saharan African populations originate from migration of AMH populations from Africa to Eurasia ∼250 kya, and subsequent admixture with Neanderthals, resulting in ∼6% AMH ancestry in Neanderthals. These results indicate that there have been multiple migration events of AMHs out of Africa and that Neanderthal and AMH gene flow has been bi-directional. Observing that genomic regions where AMHs show a depletion of Neanderthal introgression are also regions where Neanderthal genomes show a depletion of AMH introgression points to deleterious interactions between introgressed variants and background genomes in both groups-a hallmark of incipient speciation.

Evidence of housing instability identified by addresses, clinical notes, and diagnostic codes in a real-world population with substance use disorders.

Introduction: Housing instability is a social determinant of health associated with multiple negative health outcomes including substance use disorders (SUDs). Real-world evidence of housing instability is needed to improve translational research on populations with SUDs. Methods: We identified evidence of housing instability by leveraging structured diagnosis codes and unstructured clinical data from electronic health records of 20,556 patients from 2017 to 2021. We applied natural language processing with named-entity recognition and pattern matching to unstructured clinical notes with free-text documentation. Additionally, we analyzed semi-structured addresses containing explicit or implicit housing-related labels. We assessed agreement on identification methods by having three experts review of 300 records. Results: Diagnostic codes only identified 58.5% of the population identifiable as having housing instability, whereas 41.5% are identifiable from addresses only (7.1%), clinical notes only (30.4%), or both (4.0%). Reviewers unanimously agreed on 79.7% of cases reviewed; a Fleiss' Kappa score of 0.35 suggested fair agreement yet emphasized the difficulty of analyzing patients having ambiguous housing situations. Among those with poisoning episodes related to stimulants or opioids, diagnosis codes were only able to identify 63.9% of those with housing instability. Conclusions: All three data sources yield valid evidence of housing instability; each has their own inherent practical use and limitations. Translational researchers requiring comprehensive real-world evidence of housing instability should optimize and implement use of structured and unstructured data. Understanding the role of housing instability and temporary housing facilities is salient in populations with SUDs.

Comparative Risks of Potential Adverse Events Following COVID-19 mRNA Vaccination Among Older US Adults.

Importance: Head-to-head safety comparisons of the mRNA vaccines for SARS-CoV-2 are needed for decision making; however, current evidence generalizes poorly to older adults, lacks sufficient adjustment, and inadequately captures events shortly after vaccination. Additionally, no studies to date have explored potential variation in comparative vaccine safety across subgroups with frailty or an increased risk of adverse events, information that would be useful for tailoring clinical decisions. Objective: To compare the risk of adverse events between mRNA vaccines for COVID-19 (mRNA-1273 and BNT162b2) overall, by frailty level, and by prior history of the adverse events of interest. Design, Setting, and Participants: This retrospective cohort study was conducted between December 11, 2020, and July 11, 2021, with 28 days of follow-up following the week of vaccination. A novel linked database of community pharmacy and Medicare claims data was used, representing more than 50% of the US Medicare population. Community-dwelling, fee-for-service beneficiaries aged 66 years or older who received mRNA-1273 vs BNT162b2 as their first COVID-19 vaccine were identified. Data analysis began on October 18, 2022. Exposure: Dose 1 of mRNA-1273 vs BNT162b2 vaccine. Main Outcomes and Measures: Twelve potential adverse events (eg, pulmonary embolism, thrombocytopenia purpura, and myocarditis) were assessed individually. Frailty was measured using a claims-based frailty index, with beneficiaries being categorized as nonfrail, prefrail, and frail. The risk of diagnosed COVID-19 was assessed as a secondary outcome. Generalized linear models estimated covariate-adjusted risk ratios (RRs) and risk differences (RDs) with 95% CIs. Results: This study included 6 388 196 eligible individuals who received the mRNA-1273 or BNT162b2 vaccine. Their mean (SD) age was 76.3 (7.5) years, 59.4% were women, and 86.5% were White. A total of 38.1% of individuals were categorized as prefrail and 6.0% as frail. The risk of all outcomes was low in both vaccine groups. In adjusted models, the mRNA-1273 vaccine was associated with a lower risk of pulmonary embolism (RR, 0.96 [95% CI, 0.93-1.00]; RD, 9 [95% CI, 1-16] events per 100 000 persons) and other adverse events in subgroup analyses (eg, 11.0% lower risk of thrombocytopenia purpura among individuals categorized as nonfrail). The mRNA-1273 vaccine was also associated with a lower risk of diagnosed COVID-19 (RR, 0.86 [95% CI, 0.83-0.87]), a benefit that was attenuated by frailty level (frail: RR, 0.94 [95% CI, 0.89-0.99]). Conclusions and Relevance: In this cohort study of older US adults, the mRNA-1273 vaccine was associated with a slightly lower risk of several adverse events compared with BNT162b2, possibly due to greater protection against COVID-19. Future research should seek to formally disentangle differences in vaccine safety and effectiveness and consider the role of frailty in assessments of COVID-19 vaccine performance.

An open natural language processing (NLP) framework for EHR-based clinical research: a case demonstration using the National COVID Cohort Collaborative (N3C).

Despite recent methodology advancements in clinical natural language processing (NLP), the adoption of clinical NLP models within the translational research community remains hindered by process heterogeneity and human factor variations. Concurrently, these factors also dramatically increase the difficulty in developing NLP models in multi-site settings, which is necessary for algorithm robustness and generalizability. Here, we reported on our experience developing an NLP solution for Coronavirus Disease 2019 (COVID-19) signs and symptom extraction in an open NLP framework from a subset of sites participating in the National COVID Cohort (N3C). We then empirically highlight the benefits of multi-site data for both symbolic and statistical methods, as well as highlight the need for federated annotation and evaluation to resolve several pitfalls encountered in the course of these efforts.

Racial and ethnic disparities in COVID-19 booster vaccination among U.S. older adults differ by geographic region and Medicare enrollment.

Introduction: COVID-19 booster vaccines are highly effective at reducing severe illness and death from COVID-19. Research is needed to identify whether racial and ethnic disparities observed for the primary series of the COVID-19 vaccines persist for booster vaccinations and how those disparities may vary by other characteristics. We aimed to measure racial and ethnic differences in booster vaccine receipt among U.S. Medicare beneficiaries and characterize potential variation by demographic characteristics. Methods: We conducted a cohort study using CVS Health and Walgreens pharmacy data linked to Medicare claims. We included community-dwelling Medicare beneficiaries aged ≥66 years who received two mRNA vaccine doses (BNT162b2 and mRNA-1273) as of 8/1/2021. We followed beneficiaries from 8/1/2021 until booster vaccine receipt, death, Medicare disenrollment, or end of follow-up (12/31/2021). Adjusted Poisson regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) comparing vaccine uptake between groups. Results: We identified 11,339,103 eligible beneficiaries (mean age 76 years, 60% female, 78% White). Overall, 67% received a booster vaccine (White = 68.5%; Asian = 67.0%; Black = 57.0%; Hispanic = 53.3%). Compared to White individuals, Black (RR = 0.78 [95%CI = 0.78-0.78]) and Hispanic individuals (RR = 0.72 [95% = CI 0.72-0.72]) had lower rates of booster vaccination. Disparities varied by geographic region, urbanicity, and Medicare plan/Medicaid eligibility. The relative magnitude of disparities was lesser in areas where vaccine uptake was lower in White individuals. Discussion: Racial and ethnic disparities in COVID-19 vaccination have persisted for booster vaccines. These findings highlight that interventions to improve vaccine uptake should be designed at the intersection of race and ethnicity and geographic location.

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset.

Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and tirzepatide) and the phentermine-topiramate combination. To acheieve that aim, we analyzed the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AERs) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AERs involving the selected molecules were submitted to FAERS; most involved dulaglutide (n = 11,858; 37.6%) and semaglutide (n = 8249; 26.1%). In comparing semaglutide vs. the remaining molecules, the respective PRR values of the AERs 'drug abuse', 'drug withdrawal syndrome', 'prescription drug used without a prescription', and 'intentional product use issue' were 4.05, 4.05, 3.60, and 1.80 (all < 0.01). The same comparisons of semaglutide vs. the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misuse/abuse potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. The current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.