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Background: Heparin is a high-risk medication with significant variability across patients. Systematic data analysis can help hospitals improve heparin management, ensuring safe and effective anticoagulation. An opportunity exists to create a more efficient data collection process, allowing hospitals to streamline quality assurance programs. Objective: To assess the agreement between manual and electronic data abstraction for heparin quality assurance. Methods: This is a single-center, observational cohort study that evaluated patients who received therapeutic unfractionated heparin from September to November 20, 2023. Patients treated for less than 24 hours were excluded. Data were collected manually from pharmacist monitoring forms and the electronic medical record; electronic data abstraction was queried from an institutional data warehouse. The primary outcome was agreement in percentage of patients achieving a therapeutic aPTT within 24 hours. Secondary outcomes included agreement on time to therapeutic aPTT, agreement on time to therapeutic or supratherapeutic aPTT, and clinical outcomes. Results: The study included 288 patients. Manual data collection indicated 44.1% of patients were therapeutic within 24 hours, whereas electronic data collection showed 46.9% (kappa = 0.86). The kappa value for agreement of therapeutic or supratherapeutic aPTT within 24 hours was substantial (kappa = 0.69), with manual data showing 61.5% of patients therapeutic within 24 hours compared with 73.3% in electronic data. However, poor agreement was found when identifying subsequent heparin boluses (kappa = 0.13) and new venous thromboembolism cases (kappa = -0.01). Conclusions and Relevance: The metrics from the 2 data collection methods varied in reliability, ranging from highly consistent to poorly aligned. A hybrid approach, integrating manual and reliable electronic methods, has been implemented at our institution to improve efficiency. Further studies are needed to assess generalizability, and enhance electronic data capture for clinical outcomes., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Audio-visual media possesses a remarkable ability to synchronise audiences' neural, behavioural, and physiological responses. This synchronisation is considered to reflect some dimension of collective attention or engagement with the stimulus. But what is it about these stimuli that drives such strong engagement? There are several properties of media stimuli which may lead to synchronous audience response: from low-level audio-visual features, to the story itself. Here, we present a study which separates low-level features from narrative by presenting participants with the same content but in separate modalities. In this way, the presentations shared no low-level features, but participants experienced the same narrative. We show that synchrony in participants' heart rate can be driven by the narrative information alone. We computed both visual and auditory perceptual saliency for the content and found that narrative was approximately 10 times as predictive of heart rate as low-level saliency, but that low-level audio-visual saliency has a small additive effect towards heart rate. Further, heart rate synchrony was related to a separate cohorts' continuous ratings of immersion, and that synchrony is likely to be higher at moments of increased narrative importance. Our findings demonstrate that high-level narrative dominates in the alignment of physiology across viewers., (© 2024. The Author(s).)

Background: Since 2010, all non-VA hospitals performing cardiac surgeries and percutaneous interventions in Washington State have participated in the Cardiac Care Outcomes Assessment Program (COAP), a data-driven, physician-led collaborative quality improvement (QI) collaborative. Prior literature has demonstrated QI programs such as COAP can avert avoidable utilization such as hospital readmissions. However, it is unknown whether such improvements translate into economic benefits., Hypothesis: This study compared downstream healthcare costs between patients undergoing cardiac interventions for coronary artery disease (CAD) at hospitals that were and were not participating in COAP., Methods: Post hoc analysis of Medicare administrative and claims data examined 2.5 million randomly selected deidentified beneficiaries receiving a percutaneous coronary intervention or coronary artery bypass grafting between 2013 and 2020. Total costs were defined as all reimbursements paid by Medicare for up to 5 years following cardiac intervention. Because all non-VA hospitals in Washington State participated in COAP, we compared respective groups of patients receiving intervention in Washington State with all non-Washington states, adjusting for patient demographics and comorbidity. To model costs, we applied a multipart estimator, which distinguishes the impact of QI program participation due to survival and utilization while accounting for censoring., Results: Total 5-year downstream costs were $3861 lower (95% confidence interval [CI] = $1794 to $5741) among patients receiving cardiac intervention at COAP-exposed hospitals. Lower costs were largely driven by lower utilization during calendar quarters where death was not observed., Conclusions: Participation in this state-wide cardiac quality improvement program was associated with economic benefits in patients receiving intervention for CAD., (©2024 Noridian Healthcare Solutions and The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival., Methods: Patients who had cT2-4aN0-3M0 esophageal cancer treated with nCRT were identified from a trial database. Metastases detected up to 14 weeks after nCRT on 18 F-FDG-PET/CT or during surgery were categorized as oligometastases (≤3 lesions located in one single organ or one extra-regional lymph node station) or as non-oligometastases. The primary outcome was the proportion of patients with metastases after nCRT. The secondary outcomes were overall survival (OS) and the site and treatment of metastases., Results: Between 2013 and 2021, 973 patients received nCRT, and 10.3% had interval metastases. Of 100 patients, 30 (30%) had oligometastases, located mostly in non-regional lymph nodes (33.3%) or bones (26.7%). The median OS of this group was 13.8 months (95% confidence interval [CI] 9.2-27.1 months). Of 30 patients, 12 (40%) with oligometastases underwent potentially curative treatment, with a median OS of 22.8 months (95% CI 10.4-NA). The patients with non-oligometastases underwent mostly systemic therapy or BSC and had a median OS of 9 months (95% CI 7.4-10.9 months)., Conclusions: Interval metastases were detected in about 10% of patients after nCRT, underscoring the importance of re-staging with 18 F-FDG-PET/CT for those who proceed to surgery. A favorable survival might be accomplished for a subgroup of patients with oligometastases., (© 2024. The Author(s).)

Background: Home telehealth (HT) services have rapidly expanded in the Veterans Health Administration (VHA), but little is known about the real-world impact of the expansion of these services on utilization., Objective: To evaluate the impact of expanding HT diabetes services in VHA on high-cost utilization., Design: This cohort study used cross-temporal propensity score matching to identify patients with diabetes who would receive HT services (treatment group) with program expansion (treatment group) with a comparison group of patients with diabetes who did not receive HT services (control group) between 2010 and 2018. A difference-in-differences design was used to compare pre-post changes in high-cost utilization between propensity-matched groups. Data used was from the VHA's Corporate Data Warehouse., Participants: VHA patients with diabetes, n=7214 in the treatment group who received HT services, and n=1,067,138 in the control group who did not receive HT services., Main Measure(s): Emergency department (ED) visits, all-cause hospitalization, and hospitalizations for ambulatory care sensitive conditions (ACSCs)., Key Results: In the baseline period, patients in our sample had a mean age of 67 years old (SD=11 years), were 97% male, and 78% had a hemoglobin A1c (HbA1c) < 8%. The increase in HT use was associated with a net increase of ED visits per patient (0.215 95% CI [0.152, 0.279]), all-cause hospitalization (0.053 95% CI [0.032, 0.074]), and ACSC hospitalization (0.032 95% CI [0.019, 0.045])., Conclusions: Expanding HT or remote monitoring services may lead to additional needs being identified for patients, including increased access to in-person care, such as ED or hospital services., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Importance: The Medicare Competitive Bidding Program (CBP), a policy that reduced durable medical equipment prices, was implemented starting in 2011. Legislation introduced in 2024 aims to remove supplemental oxygen from the CBP because of concerns that recent decreases in oxygen prescribing are due to lower prices set by the CBP, which may have decreased supply and, in turn, limited oxygen access for patients with chronic lung diseases. However, low-value prescribing of oxygen is also prevalent in practice, and decreased oxygen prescription rates may not have necessarily caused harm. Little is known about the association of the CBP with patient use, outcomes, or spending., Objective: To examine the association between the 2011 and 2013 implementation of the CBP and supplemental oxygen use, clinical outcomes, and supplemental oxygen spending among patients with chronic obstructive pulmonary disease (COPD)., Design, Setting, and Participants: This cohort study used a difference-in-differences (DID) method to evaluate the association between implementation of the CBP and the outcomes of interest. Patients aged 65 to 100 years with COPD living in CBP areas were compared with those living in areas where the CBP was not yet or never implemented. The study included 100% fee-for-service Medicare data of beneficiaries enrolled between July 1, 2009, and December 31, 2015. The data analysis was performed between June 6, 2023, and August 16, 2024., Exposure: The 2011 and 2013 implementation cycles of the Medicare CBP., Main Outcomes and Measures: The primary outcomes were new prescriptions of oxygen during a 6-month period among beneficiaries with COPD and discontinuation of oxygen during a 6-month period among beneficiaries with COPD previously prescribed oxygen. Secondary outcomes included switches between oxygen types (gas, liquid, or concentrator), all-cause mortality, all-cause unplanned hospitalizations, COPD hospitalizations, and mean monthly allowed charges (total spending) over a 6-month period. The analysis was performed using the Callaway-Sant'Anna method, a dynamic DID model for policies with staggered implementation., Results: Among 5 753 308 Medicare beneficiaries with COPD (mean [SD] age, 79.2 [8.4] years; 55.1% female), 25.9% received supplemental oxygen for at least one 6-month period during the study. The CBP was not associated with differential changes in new oxygen prescribing (DID estimate, -0.19 percentage points; 95% CI, -2.45 to 2.08 percentage points) or oxygen discontinuations (DID estimate, -0.77 percentage points; 95% CI, -8.15 to 6.60 percentage points). Similarly, differential changes were not observed in the secondary outcomes of oxygen switches (DID estimate, -0.04 percentage points; 95% CI, -0.44 to 0.37 percentage points), all-cause mortality (DID estimate, 0.16 percentage points; 95% CI, -7.52 to 7.84 percentage points), all-cause unplanned hospitalizations (DID estimate, -0.20 percentage points; 95% CI, -10.94 to 10.53 percentage points), or COPD hospitalizations (DID estimate, -0.04 percentage points; 95% CI, -2.57 to 2.48 percentage points). Differential changes were observed for mean monthly allowed charges (DID estimate, -$326.22; 95% CI, -$434.76 to -$217.68)., Conclusions and Relevance: In this study, among beneficiaries with COPD, the Medicare CBP was associated with differentially lower spending but not differential changes in oxygen use or clinical outcomes. This study did not find evidence supporting ongoing policy efforts to remove supplemental oxygen from the CBP.

Carbonate minerals are of particular interest in paleoenvironmental research as they are an integral part of the carbon and water cycles, both of which are relevant to habitability. Given that these cycles are less constrained on Mars than they are on Earth, the identification of carbonates has been a point of emphasis for rover missions. Here, we present carbon (δ 13 C) and oxygen (δ 18 O) isotope data from four carbonates encountered by the Curiosity rover within the Gale crater. The carbon isotope values range from 72 ± 2‰ to 110 ± 3‰ Vienna Pee Dee Belemnite while the oxygen isotope values span from 59 ± 4‰ to 91 ± 4‰ Vienna Standard Mean Ocean Water (1 SE uncertainties). Notably, these values are isotopically heavy ( 13 C- and 18 O-enriched) relative to nearly every other Martian material. The extreme isotopic difference between the carbonates and other carbon- and oxygen-rich reservoirs on Mars cannot be reconciled by standard equilibrium carbonate-CO 2 fractionation, thus requiring an alternative process during or prior to carbonate formation. This paper explores two processes capable of contributing to the isotopic enrichments: 1) evaporative-driven Rayleigh distillation and 2) kinetic isotope effects related to cryogenic precipitation. In isolation, each process cannot reproduce the observed carbonate isotope values; however, a combination of these processes represents the most likely source for the extreme isotopic enrichments., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Neighborhood disadvantage has been associated with potentially preventable acute care utilization among Medicare beneficiaries, but this association has not been studied in a Medicaid population, which is important for informing more equitable care and policies for this population., Objective: To describe the association between Area Deprivation Index (ADI) and acute care utilization (including potentially preventable utilization) among Medicaid beneficiaries in Washington State., Design: Retrospective cohort study of 100% Medicaid claims. Mixed effects logistic regression was applied to estimate the association between state-level ADI decile and acute care utilization, adjusting for age, sex, self-identified race and ethnicity, Charlson Comorbidity Index, primary spoken language, individual Federal Poverty Level, homelessness, and rurality. Standard errors were clustered at the Census block group level., Participants: 1.5 million unique adult Medicaid beneficiaries enrolled for at least 11 months of a calendar year during the period 2017-2021., Main Measures: Binary measures denoting receipt of ED visits, low-acuity ED visits, hospitalizations in a calendar year., Key Results: Increasing levels of neighborhood socioeconomic disadvantage (by ADI decile) were associated with greater odds of any ED visits (adjusted odds ratio (aOR) 1.07, 95% confidence interval (CI) 1.06-1.07), low-acuity ED visits (aOR 1.08, CI 1.08-1.08), and any hospitalizations (aOR 1.02, CI 1.02-1.02)., Conclusions: Among Medicaid beneficiaries, greater neighborhood socioeconomic disadvantage was associated with increased acute care utilization, including potentially preventable utilization. These findings signal potential barriers to outpatient care access that could be amenable to future intervention by health systems and payers., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transitions to endemicity and respiratory syncytial virus (RSV) and influenza reestablish their seasonal circulation patterns, understanding their comparative burden on infants and children can guide health system responses and funding priorities., Methods: This was a population-based cohort study of children aged <5 years in Ontario, Canada, from September 2018 to August 2023 using linked health administrative databases., Results: Seasonal cohorts comprised 731 838 to 763 660 children. RSV- and influenza-related hospital admission rates immediately decreased in March 2020. In 2021-2022, RSV-related admissions rebounded but remained 8%-11% lower than prepandemic seasons, whereas 2022-2023 RSV-related admissions increased 105%-113% versus prepandemic seasons and peak admissions occurred in November versus December. Influenza did not rebound until 2022-2023, when admissions were 28%-37% higher than prepandemic seasons. Coronavirus disease 2019 (COVID-19)-related admissions remained low until 2021-2022 and were lower than RSV-related admissions across all age groups during prepandemic and pandemic seasons. By contrast, 2021-2022 COVID-19-related admissions exceeded prepandemic influenza-related admissions by 30%-40% but decreased by 45% in 2022-2023 and were lower than prepandemic influenza-related admissions, except among infants aged <12 months who remained at highest risk. There was no distinct seasonal pattern for COVID-19-related admissions during the study., Conclusions: RSV remains a major cause of childhood hospitalization. Although COVID-19 appears to be receding, its disease burden as it transitions to endemicity remains to be established. The unprecedented peaks in RSV-related hospital admissions during 2022-2023, together with the return of influenza and ongoing SARS-CoV-2 transmission, underscore the need to strengthen systems for real-time surveillance and to proactively prepare for critical healthcare scenarios., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

We hypothesized that increased cardiorespiratory fitness (CRF) slows down a person's aging, particularly in individuals with chronic airflow limitation (CAL). Participants aged ≥40 years ( n  = 78) had baseline blood DNA methylation profiled and underwent cardiopulmonary cycle exercise testing at baseline and at three years. Epigenetic clocks were calculated and tested for their association with CRF using linear regression. Differentially methylated genes associated with CRF were identified using a robust linear model. Higher CRF at baseline was associated with lower age acceleration in the epigenetic clocks DNAmAgeSkinBlood ( p = 0.016 ), DNAmGrimAge ( p = 0.012 ), and DNAmGrimAge2 ( p = 0.011 ). These effects were consistent in individuals with CAL (DNAmGrimAge p = 0.009 and DNAmGrimAge2 p = 0.007 ). CRF at three years was associated with baseline DNAmGrimAge ( p = 0.015 ) and DNAmGrimAge2 ( p = 0.011 ). Differentially methylated genes associated with CRF enriched multiple aging-related pathways, including cellular senescence. Enhancing CRF may be one intervention that can slow biological aging and improve health outcomes in chronic respiratory diseases., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Disgust is a vital emotion in the avoidance of illness. Human adults across cultures show disgust towards sources of potential contamination or pathogens, and elect to avoid their ingestion or even to look at them. Stomach rhythms appear to play an important role: disgust reduces normogastric power, and the pharmacological normalisation of gastric state reduces disgust avoidance. Human children are remarkably slow to develop disgust as measured by self-report and facial expressions. Here, we investigate whether disgust-induced avoidance (measured using eye tracking) and changes in gastric rhythm (measured using electrogastrography) exist in children aged 5 to 13 years ( N  = 45). We found that children in this bracket showed oculomotor avoidance of disgusting stimuli in a preferential-looking task, similar to adult samples in previous research. However, in contrast to adult samples in previous research, children did not show an attenuation in normogastric power. These findings could suggest that avoidance behaviour precedes gastric involvement during disgust. This would support the idea that children initially respond to parental modelling: parents set (and enforce) the social norm of disgust avoidance, and children initially conform and only later do they internalise disgust as an interoceptive signal. Alternatively, the employed stimuli could have been potent enough to induce oculomotor avoidance, but not a gastric response. Research is slim in this area, and future work should focus on elucidating the role of the stomach in disgust, and on longitudinal studies of disgust development from childhood to adolescence., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Delivering prescription digital therapeutics (ie, evidence-based interventions designed to treat, manage, or prevent disorders via websites or smartphone apps) in primary care could increase patient access to substance use disorder (SUD) treatments. However, the optimal approach to implementing prescription digital therapeutics in primary care remains unknown., Objective: This pilot study is a precursor to a larger trial designed to test whether implementation strategies (practice facilitation [PF] and health coaching [HC]) improve the delivery of prescription digital therapeutics for SUDs in primary care. This mixed methods study describes outcomes among patients in the 2 pilot clinics and presents qualitative findings on implementation., Methods: From February 10 to August 6, 2021, a total of 3 mental health specialists embedded in 2 primary care practices of the same integrated health system were tasked with offering app-based prescription digital therapeutics to patients with SUD. In the first half of the pilot, implementation activities included training and supportive tools. PF (at 1 clinic) and HC (at 2 clinics) were added in the second half. All study analyses relied on secondary data, including electronic health records and digital therapeutic vendor data. Primary outcomes were the proportion of patients reached by the prescription digital therapeutics and fidelity related to ideal use. We used qualitative methods to assess the adherence to planned activities and the barriers and facilitators to implementing prescription digital therapeutics., Results: Of all 18 patients prescribed the apps, 10 (56%) downloaded the app and activated their prescription, and 8 (44%) completed at least 1 module of content. Patients who activated the app completed 1 module per week on average. Ideal use (fidelity) was defined as completing 4 modules per week and having a monthly SUD-related visit; 1 (6%) patient met these criteria for 10 weeks (of the 12-week prescription period). A total of 5 (28%) patients had prescriptions while HC was available, 2 (11%) were successfully contacted, and both declined coaching. Clinicians reported competing clinical priorities, technical challenges, and logistically complex workflows in part because the apps required a prescription. Some pilot activities were impacted by staff turnover that coincided with the COVID-19 pandemic. The facilitators to implementation were high engagement and the perception that the apps could meet patient needs., Conclusions: The pilot study encountered the barriers to implementing prescription digital therapeutics in a real-world primary care setting, especially staffing shortages, turnover, and competing priorities for clinic teams. The larger randomized trial will clarify the extent to which PF and HC improve the implementation of digital therapeutics., Trial Registration: ClinicalTrials.gov NCT04907045; https://clinicaltrials.gov/study/NCT04907045., (©Jessica Mogk, Abisola E Idu, Jennifer F Bobb, Dustin Key, Edwin S Wong, Lorella Palazzo, Kelsey Stefanik-Guizlo, Deborah King, Tara Beatty, Caitlin N Dorsey, Ryan M Caldeiro, Angela Garza McWethy, Joseph E Glass. Originally published in JMIR Formative Research (https://formative.jmir.org), 02.09.2024.)

Background: The Veterans Health Administration increased synchronous telemedicine (video and telephone visits) in primary care in response to the COVID-19 pandemic., Objective: Our objective was to determine veteran use patterns of in-person and telemedicine primary care when all modalities were available., Design: A retrospective cohort analysis. We performed a latent class analysis of primary care visits over a 1-year period to identify veteran subgroup (i.e., class) membership based on amount of primary care use and modality used. Then, we used multinomial logistic regression with a categorical outcome to identify patient characteristics associated with class identification., Participants: A random national sample consisting of 564,580 primary care empaneled veterans in June 2021., Main Measures: Latent class membership., Key Results: We identified three latent classes: those with few primary care visits that were predominantly telephone-based (45%), intermediate number of visits of all modalities (50%), and many visits of all modalities (5%). In an adjusted model, characteristics associated with the "few" visits class, compared to the intermediate class, were older age, male sex, White race, further driving distance to primary care, higher Gagne, optimal internet speed, and unmarried status (OR 1.002, 1.52, 1.13, 1.004, 1.04, 1.05, 1.06, respectively; p < .05). Characteristics associated with membership in the "many" visits class, compared to the intermediate class, were Hispanic race, higher JEN Frailty Index and Gagne (OR 1.12, 1.11, 1.02, respectively; p < .05), and higher comorbidity by Care Assessment Need score quartile (Q2 1.73, Q3 2.80, Q4 4.12; p < 0.05)., Conclusions: Veterans accessing primary care in-person or via telemedicine do so primarily in three ways: (1) few visits, predominantly telephone; (2) intermediate visits, all modalities, (3) many visits, all modalities. We found no groups of veterans receiving a majority of primary care through video., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The menstrual cycle is a critical indicator of women's health. Early prolonged secondary amenorrhea increases risks for morbidity and mortality. Menstrual cycle research in women with HIV is inconsistent and often lacks an adequate comparison sample. We aimed to determine whether women with HIV have a higher lifetime prevalence of amenorrhea and whether this is independently associated with HIV and/or other biopsychosocial variables., Methods: With data from 2 established HIV cohorts, participants assigned female at birth were eligible if aged ≥16 years, not pregnant/lactating, and without anorexia/bulimia nervosa history. Amenorrhea was defined by self-reported history of (1) no menstrual flow for ≥12 months postmenarche not due to pregnancy/lactation, medications, or surgery or (2) early menopause or premature ovarian insufficiency. Multivariable logistic regression models explored biopsychosocial covariates of amenorrhea., Results: Overall, 317 women with HIV (median age, 47.5 years [IQR, 39.2-56.4]) and 420 women without HIV (46.2 [32.6-57.2]) were included. Lifetime amenorrhea was significantly more prevalent among women with HIV than women without HIV (24.0% vs 13.3%). In the multivariable analysis, independent covariates of amenorrhea included HIV (adjusted odds ratio, 1.70 [95% CI, 1.10-2.64]), older age (1.01 [1.00-1.04]), White ethnicity (1.92 [1.24-3.03]), substance use history (6.41 [3.75-11.1]), and current food insecurity (2.03 [1.13-3.61])., Conclusions: Nearly one-quarter of women with HIV have experienced amenorrhea, and this is associated with modifiable risk factors, including substance use and food insecurity. Care providers should regularly assess women's menstrual health and advocate for actionable sociostructural change to mitigate risks., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Caloric restriction (CR) slows biological aging and prolongs healthy lifespan in model organisms. Findings from CALERIE-2 ™ - the first ever randomized, controlled trial of long-term CR in healthy, non-obese humans - broadly supports a similar pattern of effects in humans. To expand our understanding of the molecular pathways and biological processes underpinning CR effects in humans, we generated a series of genomic datasets from stored biospecimens collected from n=218 participants during the trial. These data constitute the first publicly-accessible genomic data resource for a randomized controlled trial of an intervention targeting the biology of aging. Datasets include whole-genome SNP genotypes, and three-timepoint-longitudinal DNA methylation, mRNA, and small RNA datasets generated from blood, skeletal muscle, and adipose tissue samples (total sample n=2327). The CALERIE Genomic Data Resource described in this article is available from the Aging Research Biobank. This mult-itissue, multi-omic, longitudinal data resource has great potential to advance translational geroscience., Competing Interests: Conflict of Interest. DWB and DLC are listed as inventors of the Duke University and University of Otago invention DunedinPACE, which is licensed to TruDiagnostic. DWB is consulting CSO and SAB chair of BellSant and serves on the SAB of the Hooke Clinic.

Mesial temporal lobe epilepsy (MTLE) is a common cause of seizures, and hippocampal sclerosis (HS) is the predominant subtype. BRAFV600E mutations in MTLE-HS have only been reported infrequently. Herein, we illustrate the neurologic, radiological, and histopathological details of a patient with MTLE-HS and BRAFV600E mutant neurons. A 31-year-old male with medically refractory epilepsy presented with magnetic resonance imaging (MRI) and electroencephalography (EEG) findings typical of mesial temporal sclerosis without a mass lesion. The surgical specimens showed ILAE Type 1 HS with neurons immunopositive for BRAFV600E mutant protein distributed along the Cornu Ammonis (CA) curvature. Instead of the normal mostly perpendicular orientation of pyramidal neurons relative to the hippocampal surface, the BRAF mutant neurons were often oriented in a parallel manner. On CD34 immunostaining, sparse clusters or nodules of CD34+ stellate cells and single immunopositive stellate cells were identified. BRAFV600E or CD34 immunopositive cells were less than 1 % of total cells. The patient responded well to surgery with no further seizures after 2 years and occasional auras. Hippocampal BRAF mutant non-expansive lesion (HBNL) has been used to describe such lesions with preserved cytoarchitecture and without overt tumor mass. Others may argue for the dual pathology of HS with early ganglioglioma. Whether pre-neoplastic lesions or early tumors, these cases are important for understanding early glioneuronal tumorigenesis and suggest that BRAFV600E studies should be routinely performed on MTLE-HS cases in the setting of clinical trials. With next-generation sequencing, a FANCL deletion was detected in almost half of the alleles in our case, suggesting that many of the histologically normal-appearing cells of the hippocampus contain this alteration. FANCL mutations can result in cytogenetic anomalies and defective DNA repair and therefore may underlie the development of a low frequency BRAF alteration., Competing Interests: The authors have no conflicts of interest to report.

Background and Objectives: A proposed strategy for attenuating the return of fear is conducting exposure therapy in multiple contexts (e.g., different locations), which is believed to enhance the generalizability of safety learning. Although conducting exposure in multiple contexts can be differentiated from conducting exposure with multiple stimuli, the two strategies are often conflated. Furthermore, researchers have not yet determined whether one of these strategies, or a combination thereof, is most effective in attenuating fear renewal., Methods: Accordingly, the present treatment-analogue study examined the unique and combined effects of multiple-context and multiple-stimulus imagery-based exposure manipulations on threat expectancy, behavioral approach/anxiety, and attentional bias for threat over Zoom. Community adults (N = 134) who met diagnostic criteria for snake phobia were randomized to exposure to a single snake in multiple environmental contexts (MC), exposure to multiple snakes in a single environmental context (MS), or exposure to multiple snakes in multiple environmental contexts (MS/MC)., Results: Results revealed significant reductions in threat expectancy and behavioral anxiety, but not attentional bias for threat in all three groups. However, behavioral approach declined over the course of exposure in the MS/MC condition but remained stable in the MC and MS conditions. There were no significant group differences in behavioral approach/anxiety or attentional bias at a one-week follow-up. However, participants in the MC condition reported lower threat expectancy at a one-week follow-up than the other groups and this group difference was partially mediated by lower mean distress during exposure., Conclusions: Implications of these findings for the inhibitory retrieval theory are discussed., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

One-third of Mars' surface has shallow-buried H 2 O, but it is currently too cold for use by life. Proposals to warm Mars using greenhouse gases require a large mass of ingredients that are rare on Mars' surface. However, we show here that artificial aerosols made from materials that are readily available at Mars-for example, conductive nanorods that are ~9 micrometers long-could warm Mars >5 × 10 3 time smore effectively than the best gases. Such nanoparticles forward-scatter sunlight and efficiently block upwelling thermal infrared. Like the natural dust of Mars, they are swept high into Mars' atmosphere, allowing delivery from the near-surface. For a 10-year particle lifetime, two climate models indicate that sustained release at 30 liters per second would globally warm Mars by ≳30 kelvin and start to melt the ice. Therefore, if nanoparticles can be made at scale on (or delivered to) Mars, then the barrier to warming of Mars appears to be less high than previously thought.

Objective: The authors sought to assess workplace characteristics associated with perceived reasonable workload among behavioral health care providers in the Veterans Health Administration., Methods: The authors evaluated perceived reasonable workload and workplace characteristics from the 2019 All Employee Survey (AES; N=14,824) and 2019 Mental Health Provider Survey (MHPS; N=10,490) and facility-level staffing ratios from Mental Health Onboard Clinical Dashboard data. Nine AES and 15 MHPS workplace predictors of perceived reasonable workload, 11 AES and six MHPS demographic predictors, and facility-level staffing ratios were included in mixed-effects logistic regression models., Results: In total, 8,874 (59.9%) AES respondents and 5,915 (56.4%) MHPS respondents reported having a reasonable workload. The characteristics most strongly associated with perceived reasonable workload were having attainable performance goals (average marginal effect [AME]=0.10) in the AES and ability to schedule patients as frequently as indicated (AME=0.09) in the MHPS. Other AES characteristics significantly associated with reasonable workload included having appropriate resources, support for personal life, skill building, performance recognition, concerns being addressed, and no supervisor favoritism. MHPS characteristics included not having collateral duties that reduce care time, staffing levels not affecting care, support staff taking over some responsibilities, having spirit of teamwork, primary care-mental health integration, participation in performance discussions, well-coordinated mental health care, effective veteran programs, working at the top of licensure, and feeling involved in improving access. Facility-level staffing ratios were not significantly associated with perceived reasonable workload., Conclusions: Leadership may consider focusing resources on initiatives that support behavioral health providers' autonomy to schedule patients as clinically indicated and develop attainable performance goals., Competing Interests: The authors report no financial relationships with commercial interests.

Objective: To evaluate whether the Preventive Health Inventory (PHI)-a virtual care management intervention addressing hypertension and diabetes management implemented nationally in the Veterans Health Administration (VHA)-was delivered equitably among racial/ethnic groups and if existing inequities in hypertension and diabetes outcomes changed following PHI receipt., Data Sources and Study Setting: We used data from the VHA Corporate Data Warehouse among Veterans enrolled in primary care nationally from February 28, 2021 to March 31, 2022., Study Design: We used logistic regression to evaluate PHI receipt and hypertension and diabetes outcomes after PHI implementation among Veterans with hypertension and/or diabetes. We conducted unadjusted analyses and analyses adjusting for clinic fixed effects using dummy variables., Data Collection/extraction Methods: We identified Veterans engaged in primary care with documented race/ethnicity and hypertension and/or diabetes diagnoses in all months during the study period., Principle Findings: Prior to PHI, Non-Hispanic Black (NHB) (42.2%) and Hispanic (39.5%) Veterans were less likely to have controlled hypertension vs. Non-Hispanic White (NHW) Veterans (47.5%); NHB Veterans (32.9%) were more likely to have uncontrolled diabetes vs. NHW Veterans (25.1%). Among 1,805,658 Veterans, 5.7% NHW (N = 68,744), 5.6% NHB (N = 22,580), 10.2% Hispanic (N = 13,313), 6.2% Asian/Pacific Islander/Native Hawaiian (N = 1868), 5.1% American Indian/Native Alaskan (N = 744), and 5.6% multiple races or other race (N = 1647) Veterans received PHI. We found no significant racial inequities in PHI receipt in unadjusted and adjusted models. Hypertension and diabetes measures improved more in the intervention group compared with the group who did not receive the intervention. There were no new or worsened inequities after PHI, and in pre-/post-intervention analysis, among NHB Veterans, the inequity in uncontrolled diabetes improved by 1.9 percentage points (95% CI 0.2, 3.6)., Conclusions: Our findings suggest the PHI intervention was equitably deployed across race/ethnicity groups without significantly impacting most existing inequities in diabetes and hypertension., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Bioengineering & Translational Medicine published by American Institute of Chemical Engineers and Hoboken, USA.)

Huntingtin protein, mutated in Huntington's disease, is implicated in nucleic acid-mediated processes, yet the evidence for direct huntingtin-nucleic acid interaction is limited. Here, we show wild-type and mutant huntingtin copurify with nucleic acids, primarily RNA, and interact directly with G-rich RNAs in in vitro assays. Huntingtin RNA-immunoprecipitation sequencing from patient-derived fibroblasts and neuronal progenitor cells expressing wild-type and mutant huntingtin revealed long noncoding RNA NEAT1 as a significantly enriched transcript. Altered NEAT1 levels were evident in Huntington's disease cells and postmortem brain tissues, and huntingtin knockdown decreased NEAT1 levels. Huntingtin colocalized with NEAT1 in paraspeckles, and we identified a high-affinity RNA motif preferred by huntingtin. This study highlights NEAT1 as a huntingtin interactor, demonstrating huntingtin's involvement in RNA-mediated functions and paraspeckle regulation.

Introduction: Health systems like the Veterans Health Administration (VA) face challenges in recruiting and retaining a primary care physician workforce. This cross-sectional study of recent or current VA medical residents sought to identify determinants of intent to pursue primary care practice in VA after residency training., Methods: Residents were identified from administrative data between 2020 and 2021 and recruited via an emailed self-administered survey. Multivariable logistic regression, accounting for survey non-response, was applied to examine the association between intent to pursue VA practice and two sets of measures: VA training experiences and individual preferences for work conditions., Results: Of 268 responses received, 141 (56%) of the sample reported inclination to consider VA employment post-residency. Experiences with training in VA were rated more positively in the VA-inclined group compared to the not-inclined group. In the multivariable model, intent to practice primary care was the strongest predictor (OR 4.04, p  < 0001). Preceptors' modeling of work-life balance (OR 3.23, p  = 0.009) and perceptions of quality of clinical staff and services (OR 2.64, p  = 0.004), ability to get patients the care they need (OR 2.51, p  = 0.017), and quality of patient care (OR 2.30, p  = 0.075) were independent predictors of being in the VA inclined group., Conclusion: Overall, we found that intent to practice primary care and the quality of VA training experiences are important determinants of inclination to consider VA for employment. These results provide an important perspective relevant to medical education, the hiring and retention of the United States (U.S). primary care workforce., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Henrikson, Moldestad, Maynard, Kaboli, Reddy, Rinne, Sanders, Sterling and Wong.)

Point-of-care ultrasound (POCUS) involves the acquisition, interpretation, and immediate clinical integration of ultrasonographic imaging performed by a treating clinician. The current state of cardiac POCUS terminology is heterogeneous and ambiguous, in part because it evolved through siloed specialty practices. In particular, the medical literature and colloquial medical conversation contain a wide variety of terms that equate to cardiac POCUS. While diverse terminology aided in the development and dissemination of cardiac POCUS throughout multiple specialties, it also contributes to confusion and raises patient safety concerns. This statement is the product of a diverse and inclusive Writing Group from multiple specialties, including medical linguistics, that employed an iterative process to contextualize and standardize a nomenclature for cardiac POCUS. We sought to establish a deliberate vocabulary that is sufficiently unrelated to any specialty, ultrasound equipment, or clinical setting to enhance consistency throughout the academic literature and patient care settings. This statement (1) reviews the evolution of cardiac POCUS-related terms; (2) outlines specific recommendations, distinguishing between intrinsic and practical differences in terminology; (3) addresses the implications of these recommendations for current practice; and (4) discusses the implications for novel technologies and future research., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To quantify the association between primary care team workload satisfaction and primary care physician (PCP) turnover and examine potential mediation of workplace climate factors using survey and administrative data., Study Design: Longitudinal observational study using data from 2008 to 2016., Methods: The outcome variable was PCP turnover. The main explanatory variable was satisfaction with amount of workload. We included 7 additional workplace climate measures (eg, satisfaction with direct supervision) as mediators. We included characteristics of PCPs (eg, PCP years of experience, gender), salary, and clinic factors (eg, urban vs rural geography, community vs hospital based) as covariates., Results: US Department of Veterans Affairs (VA) PCPs working at 787 VA primary care clinics nationally were recruited for this study. Over the 9-year study period, 8362 unique PCPs were employed in the VA. The unadjusted mean quarterly turnover rate was 1.83%, and the mean (SD) workload satisfaction score was 3.58 ( 0.24) on a 5-point Likert scale over the study period. In adjusted analysis, a 1-point increase in workload satisfaction was associated with a decrease of 0.73 (95% CI, 0.36-1.10) percentage points in the probability of turnover in a calendar quarter. In the mediation analysis, we found that workload satisfaction impacted turnover through only 1 of the 7 workplace climate measures: satisfaction with direction by senior managers., Conclusions: Our study findings highlight the key role that achieving primary care workload satisfaction can play in reducing PCP turnover. Identification of direction by senior managers as an underlying mechanism is an important finding for strategic planning to mitigate PCP turnover.

Patterned morphologies, such as segments, spirals, stripes, and spots, frequently emerge during embryogenesis through self-organized coordination between cells. Yet, complex patterns also emerge in adults, suggesting that the capacity for spontaneous self-organization is a ubiquitous property of biological tissues. We review current knowledge on the principles and mechanisms of self-organized patterning in embryonic tissues and explore how these principles and mechanisms apply to adult tissues that exhibit features of patterning. We discuss how and why spontaneous pattern generation is integral to homeostasis and healing of tissues, illustrating it with examples from regenerative biology. We examine how aberrant self-organization underlies diverse pathological states, including inflammatory skin disorders and tumors. Lastly, we posit that based on such blueprints, targeted engineering of pattern-driving molecular circuits can be leveraged for synthetic biology and the generation of organoids with intricate patterns., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To describe the mental health trajectories of caregivers of children with medical complexity (CMC) and explore child characteristics associated with below-average caregiver mental health., Design: A secondary analysis of prospectively collected data from 123 caregivers of children aged <16 years with medical complexity from a multicentre randomised trial conducted from December 2016 to June 2021., Main Outcome Measure: The Patient-Reported Outcomes Measurement Information System Global Mental Health Scale was used to measure caregivers' self-reported mental health well-being. Group-based trajectory analysis was used to identify clusters of caregivers with similar changes in mental health across 24 months. Logistic regression was used to identify child-related predictors of mental health among caregivers., Results: A final model with three distinct groups was selected, corresponding to caregivers with average (n=39), moderately below-average (n=65) and severely below-average (n=19) mental health scores, all with stable trajectories and high posterior probabilities (>90%). Moderately and severely below-average caregiver mental health groups, merged into one group, were associated with a greater number of child medical technology devices (adjusted OR (aOR) 1.44, 95% CI 1.01 to 2.04), gross motor difficulties (aOR 3.51, 95% CI 1.02 to 12.05) and worse child emotional (aOR 0.93, 95% CI 0.87 to 0.99) and psychological well-being (aOR 0.93, 95% CI 0.88 to 0.99)., Conclusion: Most caregivers of CMC reported persistently below-average mental health. The intensity of caregiving, as indicated by medical technology and child functional needs, is a potential risk factor for below-average caregiver mental health. Future design and evaluation of interventions focused on support for caregivers of CMC are warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite the major roles of choroid plexus epithelial cells (CPECs) in brain homeostasis and repair, their developmental lineage and diversity remain undefined. In simplified differentiations from human pluripotent stem cells, derived CPECs (dCPECs) displayed canonical properties and dynamic multiciliated phenotypes that interacted with Aβ uptake. Single dCPEC transcriptomes over time correlated well with human organoid and fetal CPECs, while pseudotemporal and cell cycle analyses highlighted the direct CPEC origin from neuroepithelial cells. In addition, time series analyses defined metabolic (type 1) and ciliogenic dCPECs (type 2) at early timepoints, followed by type 1 diversification into anabolic-secretory (type 1a) and catabolic-absorptive subtypes (type 1b) as type 2 cells contracted. These temporal patterns were then confirmed in independent derivations and mapped to prenatal stages using human tissues. In addition to defining the prenatal lineage of human CPECs, these findings suggest new dynamic models of ChP support for the developing human brain.

Drosophila sLNv clock neurons release the neuropeptide PDF to control circadian rhythms. Strikingly, PDF content in sLNv terminals is rhythmic with a peak in the morning hours prior to the onset of activity-dependent release. Because synaptic PDF accumulation, rather than synaptic release, aligns with the late-night elevations in both sLNv neuron excitability and Ca 2+ , we explored the dependence of presynaptic neuropeptide accumulation on neuropeptide vesicle transport, electrical activity and the circadian clock. Live imaging reveals that anterograde axonal transport is constant throughout the day and capture of circulating neuropeptide vesicles rhythmically boosts presynaptic neuropeptide content hours prior to release. The late-night surge in vesicle capture, like release, requires electrical activity and results in a large releasable pool of presynaptic vesicles to support the later burst of neuropeptide release. The circadian clock is also required suggesting that it controls the switch from vesicle capture to exocytosis, which are normally coupled activity-dependent processes. This toggling of activity transduction maximizes rhythmic synaptic neuropeptide release needed for robust circadian behavior and resolves the previously puzzling delay in timing of synaptic neuropeptide release relative to changes in sLNv clock neuron physiology., Competing Interests: The authors declare no competing interests.

Recent promotion of new reactor technologies appears to disregard decades-old concerns about nuclear proliferation.

Background: DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging., Methods: BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10)., Results: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV., Conclusions: We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.

Homing pigeons (Columba livia) navigate by solar and magnetic compass, and fly home in idiosyncratic but stable routes when repeatedly released from the same location. However, when experienced pigeons fly alongside naive counterparts, their path is altered. Over several generations of turnover (pairs in which the most experienced individual is replaced with a naive one), pigeons show cumulative improvements in efficiency. Here, I show that such cumulative route improvements can occur in a much simpler system by using agent-based simulation. Artificial agents are in silico entities that navigate with a minimal cognitive architecture of goal-direction (they know roughly where the goal is), social proximity (they seek proximity to others and align headings), route memory (they recall landmarks with increasing precision), and continuity (they avoid erratic turns). Agents' behaviour qualitatively matched that of pigeons, and quantitatively fitted to pigeon data. My results indicate that naive agents benefitted from being paired with experienced agents by following their previously established route. Importantly, experienced agents also benefitted from being paired with naive agents due to regression to the goal: naive agents were more likely to err towards the goal from the perspective of experienced agents' memorised paths. This subtly biased pairs in the goal direction, resulting in intergenerational improvements of route efficiency. No cumulative improvements were evident in control studies in which agents' goal-direction, social proximity, or memory were lesioned. These 3 factors are thus necessary and sufficient for cumulative route improvements to emerge, even in the absence of sophisticated communication or thought., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Edwin S. Dalmaijer. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Respiratory syncytial virus (RSV) transmission was disrupted worldwide following the COVID-19 pandemic, and further study is required to better understand these changes., Objective: To compare observed and expected RSV hospital and intensive care unit (ICU) admission rates and characteristics of admitted children during the 2021-2022 and 2022-2023 seasons., Design, Setting, and Participants: A population-based cohort study of all children aged younger than 5 years in Ontario, Canada, July 1, 2017, through March 31, 2023, was conducted., Exposures: Individual and neighborhood-level sociodemographic and clinical characteristics were identified from administrative data, including age, palivizumab eligibility, complex medical conditions, rurality, and living in a marginalized neighborhood., Main Outcomes and Measures: The main outcome was RSV-associated hospitalization. Secondary outcomes included ICU admissions, mechanical ventilation, extracorporeal membrane oxygenation, and in-hospital death. Poisson generalized estimating equations were used to model weekly age- and sex-specific hospitalization rates and estimate expected rates in the postpandemic era; adjusted rate ratios (RRs) and 95% CIs are reported., Results: This cohort study included approximately 700 000 children per study year. Compared with prepandemic years (2017-2018, 2018-2019, and 2019-2020), the 2021-2022 RSV season peaked slightly earlier, but overall admission rates were comparable (289.1 vs 281.4-334.6 per 100 000, or approximately 2000 admissions). The 2022-2023 season peaked a month earlier and resulted in more than twice as many hospitalizations (770.0 per 100 000; n = 4977 admissions). The proportion of children admitted to an ICU in 2022-2023 (13.9%) was slightly higher than prepandemic (9.6%-11.4%); however, the population-based rate was triple the prepandemic levels (106.9 vs 27.6-36.6 per 100 000 children in Ontario). With the exception of palivizumab-eligible children, all sociodemographic and health status characteristics were associated with lower-than-expected RSV hospitalization rates in 2021-2022. In contrast, older age of patients was associated with higher-than-expected rates in 2022-2023 (ie, 24-59 months: RR, 1.90; 95% CI, 1.35-2.66)., Conclusions and Relevance: There were notable differences in RSV epidemiologic characteristics in Ontario following the COVID-19 pandemic. It is not yet clear whether and how long atypical RSV epidemics may persist. Clinicians and program planners should consider the potential for ongoing impacts to health care capacity and RSV immunization programs.

Although sex, genetics, and exposures can individually influence risk for sporadic Parkinson's disease (PD), the joint contributions of these factors to the epigenetic etiology of PD have not been comprehensively assessed. Here, we profiled sex-stratified genome-wide blood DNAm patterns, SNP genotype, and pesticide exposure in agricultural workers (71 early-stage PD cases, 147 controls) and explored replication in three independent samples of varying demographics (n = 218, 222, and 872). Using a region-based approach, we found more associations of blood DNAm with PD in females (69 regions) than in males (2 regions, Δβ adj | ≥0.03, p adj  ≤ 0.05). For 48 regions in females, models including genotype or genotype and pesticide exposure substantially improved in explaining interindividual variation in DNAm (p adj  ≤ 0.05), and accounting for these variables decreased the estimated effect of PD on DNAm. The results suggested that genotype, and to a lesser degree, genotype-exposure interactions contributed to variation in PD-associated DNAm. Our findings should be further explored in larger study populations and in experimental systems, preferably with precise measures of exposure., (© 2024. The Author(s).)

States have implemented policy changes to increase access to telemedicine services for individuals receiving Medicaid benefits. Native Hawaiian and Pacific Islander (NHPI) individuals experienced disproportionate harms from COVID-19 and have long experienced disparities in health care access compared with other racial and ethnic groups, making the issue of telemedicine access particularly salient for NHPI individuals on Medicaid. Utilizing 100% 2020-2021 Medicaid claims, we compared trends in telemedicine use between NHPI and non-Hispanic White individuals on Medicaid in Washington State and conducted a decomposition analysis to identify drivers of underlying disparities. In both years, NHPI individuals were 38%-39% less likely to use any telemedicine than White individuals after adjusting for patient- and area-level characteristics. Decomposition analysis revealed that most of this difference was due to differential effects of characteristics, rather than group differences in characteristics. Namely, several characteristics that were associated with increased telemedicine use had more muted associations for NHPI vs White individuals, such as English as the primary spoken language and female sex. These findings suggest the presence of limited acceptability of or group-specific barriers to telemedicine for NHPI individuals, including potential discrimination in being offered telemedicine visits. These issues should be understood and mitigated through close collaboration between health care leaders and NHPI communities., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Context: Home-based deaths are increasing, yet, how wealth influences where people die in the presence of disability remains unknown., Objective: To examine place of death by help with (instrumental) activities of daily living (I/ADLs) at the end of life (EOL) and the modifying role of wealth., Methods: Retrospective study of decedents from the Health and Retirement Study (n = 13,210). The exposure was intensity of help with I/ADLs at the EOL (no help/ lower intensity/higher intensity). The outcome was place of death (hospital/nursing home/home). Household wealth was an effect modifier with six categories: ≤$0, first-fifth quintile. Covariates included age, gender, race, marital status at the EOL, last place of residence, and receipt of hospice care. We used multinomial logit regression models with estimates reported as average marginal effects (AMEs)., Results: Mean age was 79.8 years; 53.2% were female. In the adjusted models, compared to not receiving help at EOL, receiving higher-intensity help was associated with a lower probability of dying in a hospital (AME = -3.8 percentage points (pp), 95% CI = -6.3 to -1.3) and a higher probability of dying at home (AME = 3.6 pp, 95% CI = 1.4-5.7). Associations were most pronounced among decedents in the top two wealth quintiles; older adults who received higher-intensity help had a lower probability of dying in a hospital (AME = -9.0 pp, 95% CI = -14.8 to -3.1), and a higher probability of dying at home (AME = 8.4 pp, 95% CI = 3.8-13.0)., Conclusion: Receiving higher intensity of help with I/ADLs was associated with lower likelihood of dying in a hospital, and higher likelihood of dying at home, particularly among older adults with greater wealth., Competing Interests: Disclosure This research used data from the HRS, which is sponsored by the National Institute on Aging (Grant U01AG009740) and is conducted by the University of Michigan. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the sponsors. The authors report there are no competing interests to declare., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Purpose: The emergence of large real-world clinical databases and tools to mine electronic medical records has allowed for an unprecedented look at large data sets with clinical and epidemiologic correlates. In clinical cancer genetics, real-world databases allow for the investigation of prevalence and effectiveness of prevention strategies and targeted treatments and for the identification of barriers to better outcomes. However, real-world data sets have inherent biases and problems (eg, selection bias, incomplete data, measurement error) that may hamper adequate analysis and affect statistical power., Methods: Here, we leverage a real-world clinical data set from a large health network for patients with breast cancer tested for variants in BRCA1 and BRCA2 (N = 12,423). We conducted data cleaning and harmonization, cross-referenced with publicly available databases, performed variant reassessment and functional assays, and used functional data to inform a variant's clinical significance applying American College of Medical Geneticists and the Association of Molecular Pathology guidelines., Results: In the cohort, White and Black patients were over-represented, whereas non-White Hispanic and Asian patients were under-represented. Incorrect or missing variant designations were the most significant contributor to data loss. While manual curation corrected many incorrect designations, a sizable fraction of patient carriers remained with incorrect or missing variant designations. Despite the large number of patients with clinical significance not reported, original reported clinical significance assessments were accurate. Reassessment of variants in which clinical significance was not reported led to a marked improvement in data quality., Conclusion: We identify the most common issues with BRCA1 and BRCA2 testing data entry and suggest approaches to minimize data loss and keep interpretation of clinical significance of variants up to date.

Genetics in Drosophila have revealed the role of neuropeptides in development and behavior. However, determining when and where neuropeptides are released has been challenging. Furthermore, the cell biology underlying neuropeptide release has largely been unexplored. Thus, it has not been possible to determine whether changes in neuropeptide immunofluorescence reflect traffic and/or release, and in neurons where such changes are not detectable, conclusions about neuropeptide release have been formulated based on the assumption that electrical and Ca 2+ recordings are accurate and quantitative predictors of release. Recently, the advent of optical detection of neuropeptides tagged with fluorescent proteins and fluorogen-activating proteins (FAPs) has made it feasible to directly image vesicle traffic and exocytosis that mediates neuropeptide release in peripheral synapses and in the brain. In fact, these approaches have led to the discovery of unexpected insights concerning neuropeptide release. Here procedures are presented for optimizing fluorescence imaging of neuropeptides tagged with green fluorescent protein or a FAP., (© 2024 Cold Spring Harbor Laboratory Press.)

Countless workers handle bodily effluvia and body envelope violations every working day, and consequentially face deeply unpleasant levels of disgust. Understanding if and how they adapt can help inform policies to improve worker satisfaction and reduce staff turnover. So far, limited evidence exist that self-reported disgust is reduced (or lower to begin with) among those employed in high-disgust environments. However, it is unclear if this is due to demand effects or translates into real behavioural changes. Here, we tested healthcare assistants (N = 32) employed in UK care homes and a control sample (N = 50). We replicated reduced self-reported pathogen disgust sensitivity in healthcare workers compared to controls. We also found it negatively correlated with career duration, suggesting long-term habituation. Furthermore, we found that healthcare assistants showed no behavioural disgust avoidance on a web-based preferential looking task (equivalent to eye tracking). Surprisingly, this extended to disgust elicitors found outside care homes, suggesting generalisation of disgust habituation. While we found no difference between bodily effluvia (core disgust) and body envelope violations (gore disgust), generalisation did not extend to other domains: self-reported sexual and moral disgust sensitivity were not different between healthcare assistants and the control group, nor was there a correlation with career duration. In sum, our work confirms that people in high-frequency disgust employment are less sensitive to pathogen disgust. Crucially, we provide preliminary evidence that this is due to a process of long-term habituation with generalisation to disgust-elicitors within the pathogen domain, but not beyond it., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Edgar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Electrophysiological studies of synaptic function do not robustly report release of neuropeptides and neurotrophins. These limitations have been overcome with the presynaptic expression of optical release reporters based on green fluorescent protein and fluorogen-activating protein. Here we describe how to image neuropeptide release in Drosophila at the neuromuscular junction and in the adult brain., (© 2024 Cold Spring Harbor Laboratory Press.)

Objective: The association between participation in a behavioral weight intervention and health expenditures has not been well characterized. We compared Veterans Affairs (VA) expenditures of individuals participating in MOVE!, a VA behavioral weight loss program, and matched comparators 2 years before and 2 years after MOVE! initiation., Methods: Retrospective cohort study of Veterans who had one or more MOVE! visits in 2008-2017 who were matched contemporaneously to up to 3 comparators with overweight or obesity through sequential stratification on an array of patient characteristics, including sex. Baseline patient characteristics were compared between the two cohorts through standardized mean differences. VA expenditures in the 2 years before MOVE! initiation and 2 years after initiation were modeled using generalized estimating equations with a log link and distribution with variance proportional to the standard deviation (gamma)., Results: MOVE! participants (n=499,696) and comparators (n=1,336,172) were well-matched, with an average age of 56, average body mass index of 35, and similar total VA expenditures in the fiscal year before MOVE! initiation ($9662 for MOVE! participants and $10,072 for comparators, standardized mean difference=-0.019). MOVE! participants had total expenditures that were statistically lower than matched comparators in the 6 months after initiation but modestly higher in the 6 months to 2 years after initiation, though differences were small in magnitude (1.0%-1.6% differences)., Conclusions: The VA's system-wide behavioral weight intervention did not realize meaningful short-term health care cost savings for participants., Competing Interests: M.L.M. reports research grants from NIH and VA HSR&D and ownership of Amgen stock due to his spouse’s employment. Also, he was supported by a Senior Research Career Scientist award (RCS 10-391), all from VA HSR&D. V.A.S. reports research grants from NIH and VA HSR&D. A.H. reports research grants from NIH and VA HSR&D. Also, she was supported by a Career Development Award (IK2 HX003359). The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The Veterans Choice Program (VCP) of the Veterans Health Administration (VHA) allowed eligible veterans to use their benefits with participating providers outside the VHA. The authors aimed to identify characteristics of veterans with depression who used or did not use mental health care through the VCP., Methods: In this cross-sectional study, the authors analyzed secondary data from the national VHA Corporate Data Warehouse. VHA administrative data were linked with VCP claims to examine characteristics of VCP-eligible veterans with depression. The study sample included 595,943 unique veterans who were enrolled in the VHA before 2013, were eligible for the VCP in 2016, were alive in 2018, and had an assessed Patient Health Questionnaire-9 (PHQ-9) score or depressive disorder diagnosis documented in the VHA between 2016 and 2018., Results: Veterans who used the VCP had lower medical comorbidity scores and lived in less socioeconomically disadvantaged counties, compared with veterans who received only VHA care. VCP veterans were also more likely to have a PHQ-9 score assessment and to have higher mean depression scores. Mean counts of annual mental health visits per 1,000 veterans were markedly higher for direct VHA care than for care provided via the VCP. As a percentage of the total counts of visits per 1,000 veterans across the VCP and VHA, residential programs and outpatient procedures were the services that were most frequently delivered through the VCP., Conclusions: Between 2016 and 2018, the VCP was used primarily to augment mental health care provided by the VHA, rather than to fill a gap in care., Competing Interests: Dr. Carlo reports receiving consulting fees from Otsuka Pharmaceutical. The other authors report no financial relationships with commercial interests.

Importance: The COVID-19 pandemic caused significant declines in the quality of preventive and chronic disease care. The Veterans Health Administration (VHA) used the Preventive Health Inventory (PHI), a multicomponent care management intervention, to catch up on care disrupted by the pandemic., Objective: To identify key factors associated with PHI use., Design, Setting, and Participants: This cohort study of veterans receiving primary care used administrative data from national VHA primary care clinics for February 1, 2021, through February 1, 2022., Exposure: Patient PHI receipt., Main Outcomes and Measures: The main outcomes were patient, practitioner, and clinic factors associated with PHI receipt. Binomial generalized linear models with fixed effects for clinic were used to analyze factors associated with receipt of PHI. Least absolute shrinkage and selection operator procedures were used for variable selection., Results: A total of 4 358 038 veterans (mean [SD] age, 63.7 [16.0] years; 90% male; 76% non-Hispanic White) formed the study cohort, of whom 389 757 (9%) received the PHI. Veterans who received the PHI had higher mean Care Assessment Need (CAN) scores, which indicate the likelihood of hospitalization or death within 1 year (mean [SD], 51.9 [28.6] vs 47.2 [28.6]; standardized mean difference [SMD], -0.16). They were also more likely to live in urban areas (77% vs 64%; SMD, 0.28) and have a shorter drive distance to primary care (mean [SD], 13.2 [12.4] vs 15.7 [14.6] miles; SMD, 0.19). The mean outpatient use was higher among PHI recipients compared with non-PHI recipients (mean [SD], 18.4 [27.8] vs 15.1 [24.1] visits; SMD, -0.13). In addition, veterans with primary care practitioners with higher caseloads were more likely to receive the PHI (mean [SD], 778 [231] vs 744 [249] patients; SMD, -0.14), and they were more likely to be seen at larger clinics (mean [SD], 9670 [6876] vs 8786 [6892] patients; SMD, -0.13). Prior outpatient use and CAN score were associated with PHI receipt in the final model., Conclusions and Relevance: In this cohort study of the VHA's PHI, patients with higher CAN scores and more outpatient use in the previous year were more likely to receive the PHI. This study identifies potential intervention points to improve care coordination for veterans.

Importance: Unintentional injury, suicide, and homicide are leading causes of death among young females. Teen pregnancy may be a marker of adverse life experiences., Objective: To evaluate the risk of premature mortality from 12 years of age onward in association with number of teen pregnancies and age at pregnancy., Design, Setting, and Participants: This population-based cohort study was conducted among all females alive at 12 years of age from April 1, 1991, to March 31, 2021, in Ontario, Canada (the most populous province, which has universal health care and data collection). The study period ended March 31, 2022., Exposures: The main exposure was number of teen pregnancies between 12 and 19 years of age (0, 1, or ≥2). Secondary exposures included how the teen pregnancy ended (birth or miscarriage vs induced abortion) and age at first teen pregnancy., Main Outcomes and Measures: The main outcome was all-cause mortality starting at 12 years of age. Hazard ratios (HRs) were adjusted for year of birth, comorbidities at 9 to 11 years of age, and area-level education, income level, and rurality., Results: Of 2 242 929 teenagers, 163 124 (7.3%) experienced a pregnancy at a median age of 18 years (IQR, 17-19 years). Of those with a teen pregnancy, 60 037 (36.8%) ended in a birth (of which 59 485 [99.1%] were live births), and 106 135 (65.1%) ended in induced abortion. The median age at the end of follow-up was 25 years (IQR, 18-32 years) for those without a teen pregnancy and 31 years (IQR, 25-36 years) for those with a teen pregnancy. There were 6030 deaths (1.9 per 10 000 person-years [95% CI, 1.9-2.0 per 10 000 person-years]) among those without a teen pregnancy, 701 deaths (4.1 per 10 000 person-years [95% CI, 3.8-4.5 per 10 000 person-years]) among those with 1 teen pregnancy, and 345 deaths (6.1 per 10 000 person-years [95% CI, 5.5-6.8 per 10 000 person-years]) among those with 2 or more teen pregnancies; adjusted HRs (AHRs) were 1.51 (95% CI, 1.39-1.63) for those with 1 pregnancy and 2.14 (95% CI, 1.92-2.39) for those with 2 or more pregnancies. Comparing those with vs without a teen pregnancy, the AHR for premature death was 1.25 (95% CI, 1.12-1.40) from noninjury, 2.06 (95% CI, 1.75-2.43) from unintentional injury, and 2.02 (95% CI, 1.54-2.65) from intentional injury., Conclusions and Relevance: In this population-based cohort study of 2.2 million female teenagers, teen pregnancy was associated with future premature mortality. It should be assessed whether supports for female teenagers who experience a pregnancy can enhance the prevention of subsequent premature mortality in young and middle adulthood.

Background: Anti-obesity medications (AOMs) can be initiated in conjunction with participation in the VA national behavioral weight management program, MOVE!, to help achieve clinically meaningful weight loss., Objective: To compare weight change between Veterans who used AOM + MOVE! versus MOVE! alone and examine AOM use, duration, and characteristics associated with longer duration of use., Design: Retrospective cohort study using VA electronic health records., Participants: Veterans with overweight or obesity who participated in MOVE! from 2008-2017., Main Measures: Weight change from baseline was estimated using marginal structural models up to 24 months after MOVE! initiation. The probability of longer duration of AOM use (≥ 180 days) was estimated via a generalized linear mixed model., Results: Among MOVE! participants, 8,517 (1.6%) used an AOM within 24 months after MOVE! initiation with a median of 90 days of cumulative supply. AOM + MOVE! users achieved greater weight loss than MOVE! alone users at 6 (3.2% vs. 1.6%, p < 0.001), 12 (3.4% vs. 1.4%, p < 0.001), and 24 months (2.7% vs. 1.5%, p < 0.001), and had a greater probability of achieving ≥ 5% weight loss at 6 (38.8% vs. 26.0%, p < 0.001), 12 (43.1% vs. 28.4%, p < 0.001), and 24 months (40.4% vs. 33.3%, p < 0.001). Veterans were more likely to have ≥ 180 days of supply if they were older, exempt from medication copays, used other medications with significant weight-gain, significant weight-loss, or modest weight-loss side effects, or resided in the West North Central or Pacific regions. Veterans were less likely to have ≥ 180 days of AOM supply if they had diabetes or initiated MOVE! later in the study period., Conclusions: AOM use following MOVE! initiation was uncommon, and exposure was time-limited. AOM + MOVE! was associated with a higher probability of achieving clinically significant weight loss than MOVE! alone., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Virtual care, including synchronous and asynchronous telehealth, remote patient monitoring, and the collection and interpretation of patient-generated health data (PGHD), has the potential to transform healthcare delivery and increase access to care. The Veterans Health Administration (VHA) Office of Health Services Research and Development (HSR&D) convened a State-of-the-Art (SOTA) Conference on Virtual Care to identify future virtual care research priorities. Participants were divided into three workgroups focused on virtual care access, engagement, and outcomes. In this article, we report the findings of the Outcomes Workgroup. The group identified virtual care outcome areas with sufficient evidence, areas in need of additional research, and areas that are particularly well-suited to be studied within VHA. Following a rigorous process of literature review and consensus, the group focused on four questions: (1) What outcomes of virtual care should we be measuring and how should we measure them?; (2) how do we choose the "right" care modality for the "right" patient?; (3) what are potential consequences of virtual care on patient safety?; and (4) how can PGHD be used to benefit provider decision-making and patient self-management?. The current article outlines key conclusions that emerged following discussion of these questions, including recommendations for future research., (© 2023. The Author(s).)

Rationale: Prescription formularies specify which medications are available to patients. Formularies change frequently, potentially forcing patients to switch medications for nonclinical indications (nonmedical switching). Nonmedical switching is known to impact disease control and adherence. The consequences of nonmedical switching have not been rigorously studied in COPD., Methods: We conducted a cohort study of Veterans with COPD on inhaler therapy in January 2016 when formoterol was removed from the Department of Veterans Affairs (VA) national formulary. A 2-point difference-in-differences analysis using multivariable negative binomial and generalized linear models was performed to estimate the association of the formulary change with patient outcomes in the 6 months before and after the change. Our primary outcome was the number of COPD exacerbations in 6 months, with secondary outcomes of total health care encounters and encounter-related costs in 6 months., Results: We identified 10,606 Veterans who met our inclusion criteria, of which 409 (3.9%) experienced nonmedical switching off formoterol. We did not identify a change in COPD exacerbations (-0.04 exacerbations; 95% confidence interval [CI] -0.12, 0.03) associated with the formulary change. In secondary outcome analysis, we did not observe a change in the number of health care encounters (-0.12 visits; 95% CI -1.00, 0.77) or encounter-related costs ($369; 95% CI -$1141, $1878)., Conclusions: Among COPD patients on single inhaler therapy, nonmedical inhaler switches due to formulary discontinuation of formoterol were not associated with changes in COPD exacerbations, encounters, or encounter-related costs. Additional research is needed to confirm our findings in more severe disease and other settings., (JCOPDF © 2024.)