VAMP2 chaperones α-synuclein in synaptic vesicle co-condensates.

α-Synuclein (α-Syn) aggregation is closely associated with Parkinson's disease neuropathology. Physiologically, α-Syn promotes synaptic vesicle (SV) clustering and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly. However, the underlying structural and molecular mechanisms are uncertain and it is not known whether this function affects the pathological aggregation of α-Syn. Here we show that the juxtamembrane region of vesicle-associated membrane protein 2 (VAMP2)-a component of the SNARE complex that resides on SVs-directly interacts with the carboxy-terminal region of α-Syn through charged residues to regulate α-Syn's function in clustering SVs and promoting SNARE complex assembly by inducing a multi-component condensed phase of SVs, α-Syn and other components. Moreover, VAMP2 binding protects α-Syn against forming aggregation-prone oligomers and fibrils in these condensates. Our results suggest a molecular mechanism that maintains α-Syn's function and prevents its pathological amyloid aggregation, the failure of which may lead to Parkinson's disease.

Male Rejuvenation: Injectables.

The use of injectables can effectively treat the areas of greatest facial esthetic concern in males. Due to significant differences in the facial anatomy of men compared to women, treatment strategy, dosage, and technique differs. This article will review the pharmacology, preparation, pertinent anatomy, technique, risks, and adverse events associated with injectable agents emphasizing unique differences in male anatomy and esthetics.

An exploration into the relationship between insomnia and repetitive negative thinking among cancer survivors.

OBJECTIVE: Insomnia and repetitive negative thinking (RNT) are both prevalent among cancer survivors, yet little work has investigated their interrelationship. To explore the hypothesis that RNT and insomnia are related, we conducted secondary analyses on data from a pilot clinical trial of cognitive behavioral therapy for insomnia (CBT-I) for cancer survivors. METHODS: This study analyzed survey data from 40 cancer survivors with insomnia who participated in a pilot randomized trial of CBT-I. Correlations and linear regression models were used to determine associations between aspects of RNT and related constructs (fear of cancer recurrence [FCR], cancer-specific rumination, worry, and intolerance of uncertainty) and sleep (insomnia and sleep quality), while accounting for psychiatric symptoms such as anxiety and depression. Treatment-related change in RNT was examined using a series of linear mixed models. RESULTS: Evidence for an association between RNT and insomnia among cancer survivors emerged. Higher levels of FCR and cancer-related rumination were correlated with more severe insomnia symptoms and worse sleep quality. Notably, FCR levels predicted insomnia, even after controlling for anxiety and depression. Results identified potential benefits and limitations of CBT-I in addressing RNT that should be examined more thoroughly in future research. CONCLUSIONS: RNT is a potential target to consider in insomnia treatment for cancer survivors.

Care Fragmentation, Social Determinants of Health, and Postoperative Mortality in Older Veterans.

INTRODUCTION: Veterans Affairs Surgical Quality Improvement Program (VASQIP) benchmarking algorithms helped the Veterans Health Administration (VHA) reduce postoperative mortality. Despite calls to consider social risk factors, these algorithms do not adjust for social determinants of health (SDoH) or account for services fragmented between the VHA and the private sector. This investigation examines how the addition of SDoH change model performance and quantifies associations between SDoH and 30-d postoperative mortality. METHODS: VASQIP (2013-2019) cohort study in patients ≥65 y old with 2-30-d inpatient stays. VASQIP was linked to other VHA and Medicare/Medicaid data. 30-d postoperative mortality was examined using multivariable logistic regression models, adjusting first for clinical variables, then adding SDoH. RESULTS: In adjusted analyses of 93,644 inpatient cases (97.7% male, 79.7% non-Hispanic White), higher proportions of non-veterans affairs care (adjusted odds ratio [aOR] = 1.02, 95% CI = 1.01-1.04) and living in highly deprived areas (aOR = 1.15, 95% CI = 1.02-1.29) were associated with increased postoperative mortality. Black race (aOR = 0.77, CI = 0.68-0.88) and rurality (aOR = 0.87, CI = 0.79-0.96) were associated with lower postoperative mortality. Adding SDoH to models with only clinical variables did not improve discrimination (c = 0.836 versus c = 0.835). CONCLUSIONS: Postoperative mortality is worse among Veterans receiving more health care outside the VA and living in highly deprived neighborhoods. However, adjusting for SDoH is unlikely to improve existing mortality-benchmarking models. Reduction efforts for postoperative mortality could focus on alleviating care fragmentation and designing care pathways that consider area deprivation. The adjusted survival advantage for rural and Black Veterans may be of interest to private sector hospitals as they attempt to alleviate enduring health-care disparities.

Issues in Distinguishing Sex and Gender in Surgical Registries: A NSQIP and VASQIP Analysis.

BACKGROUND: Surgical registries do not have separate sex (the biological construct) and gender identity variables. We examined procedures specific to sexually dimorphic anatomy, such as ovaries, testes, and other reproductive organs, to identify "discrepancies" between recorded sex and the anatomy of a procedure. These "discrepancies" would represent a structural limitation of surgical registries, one that may unintentionally perpetuate health inequities. STUDY DESIGN: Retrospective cohort study using 2015-2019 NSQIP and 2016-2019 VASQIP. Surgeries were limited to procedures pertaining to anatomy that is either specifically male (CPT codes 54000-55899) or female (56405-59899). The sex recorded in the surgical registries, often automatically retrieved from electronic health record data, was compared to the specified anatomy of each procedure to quantify discrepancies. RESULTS: 575,956 procedures were identified specific to sexually dimorphic anatomy (549,411 NSQIP; 26,545 VASQIP). Of those, 2,137 recorded a sex discordant with the anatomy specified by the surgical procedure (rates 0.4% in NSQIP; 0.2% in VASQIP). Procedures specific to female anatomy with recorded male sex were more frequent (82.6% in NSQIP; 98.4% in VASQIP) than procedures specific to male anatomy with recorded female sex. CONCLUSIONS: Discrepancies between recorded sex and the anatomy of a surgical procedure were limited. However, because sex in surgical registries is often directly acquired from electronic health record data, these cases likely represent transgender, gender diverse, or living with a difference of sex development (intersex) patients. As these populations increase and continue to seek healthcare, precise measurement of sex, gender identity, and legal sex is necessary for adequate risk adjustment, risk prediction, and surgical outcome benchmarking for optimal care.

Videoconference-delivered group Cognitive Behavioral Stress Management for ME/CFS patients who present with severe PEM: A randomized controlled trial.

Background: In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), post-exertional malaise (PEM) is associated with greater distress and symptoms. Cognitive Behavioral Stress Management (CBSM) has demonstrated beneficial effects for ME/CFS and may mitigate stress-related triggers of PEM. We tested a virtual CBSM intervention to increase access, and we report on its effects on stress and symptoms in ME/CFS patients with severe PEM. Methods: Data were from a randomized controlled trial (NCT01650636) comparing 10-week videoconference-delivered group CBSM (V-CBSM, n=75) to a 10-week Health Information active control (V-HI, n=75) in Fukuda criteria ME/CFS patients (71 classified as highPEM, 79 lowPEM). Linear regression explored PEM-by-Treatment interactions on overall symptom frequency and intensity, perceived stress, and fatigue-specific interference and intensity, at 5-month follow-up. Logistic regression tested V-CBSM effects on 5-month PEM status. Analyses controlled for age, gender, race/ethnicity, mode of symptom onset, and time since diagnosis. Results: The sample was middle-aged (47.96±10.89 years), mostly women (87%) and non-Hispanic White (65%), with no group differences on these variables or baseline PEM. For highPEM patients, V-CBSM (versus V-HI) demonstrated medium to large effects on follow-up symptom frequency, symptom intensity, fatigue interference, and fatigue intensity (p's < .05) and trending to significant reductions in perceived stress (p =.07). Differences were not evident for lowPEM patients. Treatment predicted follow-up PEM status at a trend (p = .058), with patients receiving V-CBSM demonstrating half the risk of highPEM classification versus V-HI. Conclusions: V-CBSM demonstrates benefits for ME/CFS patients presenting with severe PEM and may reduce the expression of PEM over time.

Adaptation of the Risk Analysis Index for Frailty Assessment Using Diagnostic Codes.

Importance: Frailty is associated with adverse outcomes after even minor physiologic stressors. The validated Risk Analysis Index (RAI) quantifies frailty; however, existing methods limit application to in-person interview (clinical RAI) and quality improvement datasets (administrative RAI). Objective: To expand the utility of the RAI utility to available International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) administrative data, using the National Inpatient Sample (NIS). Design, Setting, and Participants: RAI parameters were systematically adapted to ICD-10-CM codes (RAI-ICD) and were derived (NIS 2019) and validated (NIS 2020). The primary analysis included survey-weighed discharge data among adults undergoing major surgical procedures. Additional external validation occurred by including all operative and nonoperative hospitalizations in the NIS (2020) and in a multihospital health care system (UPMC, 2021-2022). Data analysis was conducted from January to May 2023. Exposures: RAI parameters and in-hospital mortality. Main Outcomes and Measures: The association of RAI parameters with in-hospital mortality was calculated and weighted using logistic regression, generating an integerized RAI-ICD score. After initial validation, thresholds defining categories of frailty were selected by a full complement of test statistics. Rates of elective admission, length of stay, hospital charges, and in-hospital mortality were compared across frailty categories. C statistics estimated model discrimination. Results: RAI-ICD parameters were weighted in the 9 548 206 patients who were hospitalized (mean [SE] age, 55.4 (0.1) years; 3 742 330 male [weighted percentage, 39.2%] and 5 804 431 female [weighted percentage, 60.8%]), modeling in-hospital mortality (2.1%; 95% CI, 2.1%-2.2%) with excellent derivation discrimination (C statistic, 0.810; 95% CI, 0.808-0.813). The 11 RAI-ICD parameters were adapted to 323 ICD-10-CM codes. The operative validation population of 8 113 950 patients (mean [SE] age, 54.4 (0.1) years; 3 148 273 male [weighted percentage, 38.8%] and 4 965 737 female [weighted percentage, 61.2%]; in-hospital mortality, 2.5% [95% CI, 2.4%-2.5%]) mirrored the derivation population. In validation, the weighted and integerized RAI-ICD yielded good to excellent discrimination in the NIS operative sample (C statistic, 0.784; 95% CI, 0.782-0.786), NIS operative and nonoperative sample (C statistic, 0.778; 95% CI, 0.777-0.779), and the UPMC operative and nonoperative sample (C statistic, 0.860; 95% CI, 0.857-0.862). Thresholds defining robust (RAI-ICD <27), normal (RAI-ICD, 27-35), frail (RAI-ICD, 36-45), and very frail (RAI-ICD >45) strata of frailty maximized precision (F1 = 0.33) and sensitivity and specificity (Matthews correlation coefficient = 0.26). Adverse outcomes increased with increasing frailty. Conclusion and Relevance: In this cohort study of hospitalized adults, the RAI-ICD was rigorously adapted, derived, and validated. These findings suggest that the RAI-ICD can extend the quantification of frailty to inpatient adult ICD-10-CM-coded patient care datasets.

Preclinical development of EXT608, an investigational parathyroid hormone derivative with extended half-life for the treatment of hypoparathyroidism.

Hypoparathyroidism, a deficiency of parathyroid hormone (PTH), results in hypocalcemia, hyperphosphatemia, and hypercalciuria. The disease is poorly controlled by calcium and vitamin D supplements or native PTH(1-84) replacement therapy. A version of PTH is being developed using D-VITylation technology, whereby vitamin D is conjugated to a therapeutic peptide, which confers a long plasma half-life by virtue of binding to the abundant vitamin D binding protein (DBP). D-VITylation of PTH caused no reduction in activity at the PTHR1 receptor, and resulted in a plasma elimination half-life of 7-15 h in rats and 24-32 h in cynomolgus monkeys. Analysis of steady-state pharmacokinetics as a function of dose showed flat profiles with smaller peak:trough ratios at low doses, indicative of slower subcutaneous absorption. In thyroparathyroidectomized (TPTx) rats, PTH(1-34)-vitamin D conjugates restored serum calcium and phosphate levels into the normal range over the 24 h dosing period, and increased bone turnover markers and reduced bone mineral density. Urinary calcium was initially elevated, but normalized by the end of treatment on day 27. In healthy monkeys, a single dose of PTH(1-34)-vitamin D conjugates elevated serum calcium levels above the normal range for a period of 24-48 h while simultaneously reducing urinary calcium. Therefore, the lead compound, EXT608, is a promising candidate as a therapeutic that can truly mimic the endogenous activity of PTH and warrants further study in patients with hypoparathyroidism.

The Association Between Type of Insurance Plan, Out-of-Pocket Cost, and Adherence to Antihypertensive Medications in Medicare Supplement Insurance Enrollees.

BACKGROUND: Medicare supplement insurance, or Medigap, covers 21% of Medicare beneficiaries. Despite offsetting some out-of-pocket (OOP) expenses, remaining OOP costs may pose a barrier to medication adherence. This study aims to evaluate how OOP costs and insurance plan types influence medication adherence among beneficiaries covered by Medicare supplement plans. METHODS: We conducted a retrospective analysis of the Merative MarketScan Medicare Supplement Database (2017-2019) in Medigap enrollees (≥65 years) with hypertension. The proportion of days covered (PDC) was a continuous measure of medication adherence and was also dichotomized (PDC ≥0.8) to quantify adequate adherence. Beta-binomial and logistic regression models were used to estimate associations between these outcomes and insurance plan type and log-transformed OOP costs, adjusting for patient characteristics. RESULTS: Among 27,407 patients with hypertension, the average PDC was 0.68 ±â€…0.31; 47.5% achieved adequate adherence. A mean $1 higher in 30-day OOP costs were associated with a 0.06 (95% confidence intervals [CIs]: -0.09 to -0.03) lower probability of adequate adherence, or a 5% (95% CI: 4%-7%) decrease in PDC. Compared with comprehensive plan enrollees, the odds of adequate adherence were lower among those with point-of-service plans (odds ratio [OR]: 0.69, 95% CI: 0.62-0.77), but higher among those with preferred provider organization (PPO) plans (OR: 1.08, 95% CI: 1.01-1.15). Moreover, the association between OOP costs and PDC was significantly greater for PPO enrollees. CONCLUSIONS: While Medicare supplement insurance alleviates some OOP costs, different insurance plans and remaining OOP costs influence medication adherence. Reducing patient cost-sharing may improve medication adherence.

Social Determinants of Long-Term Opioid Use Following Total Knee Arthroplasty.

Total knee arthroplasty (TKA) risks persistent pain and long-term opioid use (LTO). The role of social determinants of health (SDoH) in LTO is not well established. We hypothesized that SDoH would be associated with postsurgical LTO after controlling for relevant demographic and clinical variables. This study utilized data from the Veterans Affairs Surgical Quality Improvement Program, VA Corporate Data Warehouse, and Centers for Medicare and Medicaid Services, including Veterans aged ≥ 65 who underwent elective TKA between 2013 and 2019 with no postsurgical complications or history of significant opioid use. LTO was defined as > 90 days of opioid use beginning within 90 days postsurgery. SDoH variables included the Area Deprivation Index, rurality, and housing instability in the last 12 months identified via medical record screener or International Classification of Diseases, Tenth Revision codes. Multivariable risk adjustment models controlled for demographic and clinical characteristics. Of the 9,064 Veterans, 97% were male, 84.2% white, mean age was 70.6 years, 46.3% rural, 11.2% living in highly deprived areas, and 0.9% with a history of homelessness/housing instability. Only 3.7% (n = 336) developed LTO following TKA. In a logistic regression model of only SDoH variables, housing instability (odds ratio [OR] = 2.38, 95% confidence interval [CI]: 1.09-5.22) and rurality conferred significant risk for LTO. After adjusting for demographic and clinical variables, LTO was only associated with increasing days of opioid supply in the year prior to surgery (OR = 1.52, 95% CI: 1.43-1.63 per 30 days) and the initial opioid fill (OR = 1.07; 95% CI: 1.06-1.08 per day). Our primary hypothesis was not supported; however, our findings do suggest that patients with housing instability may present unique challenges for postoperative pain management and be at higher risk for LTO.

Novel Skin Prep Technique Reduces OR Preparation Times in a Randomized Trial for Podiatric and Orthopedic Procedures.

The primary objectives of any high-volume surgery department should be patient safety, block time utilization and operating room efficiency. Reducing preparation time in the OR prior to actual surgery can improve operating room efficiency and utilization, but only if patient safety can be maintained. With this goal, this study evaluated a novel skin preparation technique using a device named ULTRAPREP™, a sterile, medical-grade plastic bag that is applied to the upper or lower extremity in the pre-operative holding area which allows for skin disinfection outside the OR (referred to as "disinfection bag"). The study compared preparation times required in the OR and antiseptic efficiency (through Colony Forming Units (CFU) counts) for traditional methods versus using the disinfection bag on a total of 115 patients undergoing podiatric or orthopedic surgeries (upper and lower extremities) in one hospital. The disinfection bag reduced skin preparation time in the OR from 16.8±3.5min to 10.9±2.7min, which was a 35.2% reduction, and was statistically significant (p<0.01). Skin antisepsis met safety standards of <15 CFUs for all cases regardless of preparation type at 48h and 72h. There was no statistical difference in CFU levels between the traditional and disinfection bag methods at 48h or 72h (p>0.11). Therefore, ULTRAPREP™ has shown the ability to decrease operating room time while keeping surgical site infection rates to a minimum. Minimizing activities in the OR optimizes use of this costly resource and brings overall savings to the surgery department.

The association between frailty and outcomes following ruptured abdominal aortic aneurysm repair.

OBJECTIVE: Endovascular aortic repair (EVAR) is a less invasive method than the more physiologically stressful open surgical repair (OSR) for patients with anatomically appropriate abdominal aortic aneurysms (AAAs). Early postoperative outcomes are associated with both patients; physiologic reserve and the physiologic stresses of the surgical intervention. Among frail patients with reduced physiologic reserve, the stress of an aortic rupture in combination with the stress of an operative repair are less well tolerated, raising the risk of complications and mortality. This study aims to evaluate the difference in association between frailty and outcomes among patients undergoing minimally invasive EVAR and the physiologically more stressful OSR for ruptured AAAs (rAAAs). METHODS: Our retrospective cohort study included adults undergoing rAAA repair in the Vascular Quality Initiative from 2010 to 2022. The validated Risk Analysis Index (RAI) (robust, ≤20; normal, 21-29; frail, 30-39; very frail, ≥40) quantified frailty. The association between the primary outcome of 1-year mortality and frailty status as well as repair type were compared using multivariable Cox models generating adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Interaction terms evaluated the association's moderation. RESULTS: We identified 5806 patients (age, 72 ± 9 years; 77% male; EVAR, 65%; robust, 6%; normal, 48%; frail, 36%; very, frail 10%) with a 53% observed 1-year mortality rate following rAAA repair. OSR (aHR, 1.43; 95% CI, 1.19-1.73) was associated with increased 1-year mortality when compared with EVAR. Increasing frailty status (frail aHR, 1.26; 95% CI, 1.00-1.59; very frail aHR, 1.64; 95% CI, 1.26-2.13) was associated with increased 1-year mortality, which was moderated by repair type (P-interaction < .05). OSR was associated with increased 1-year mortality in normal (aHR, 1.49; 95% CI, 1.20-1.87) and frail (aHR, 1.51; 95% CI, 1.20-1.89), but not among robust (aHR, 0.88; 95% CI, 0.59-1.32) and very frail (aHR, 1.29; 95% CI, 0.97-1.72) patients. CONCLUSIONS: Frailty and OSR were associated with increased adjusted risk of 1-year mortality following rAAA repair. Among normal and frail patients, OSR was associated with an increased adjusted risk of 1-year mortality when compared with EVAR. However, there was no difference between OSR and EVAR among robust patients who can well tolerate the stress of OSR and among very frail patients who are unable to withstand the surgical stress from rAAA regardless of repair type.

Development and feasibility of a virtual, synchronous mind-body resiliency intervention for fathers of children and youth with special healthcare needs.

Background: Fathers of children and youth with special healthcare needs (FCYSHCN) are an overlooked population at risk for chronic stress. Mind-body practices offer a patient-centered approach to foster coping and resiliency, yet low engagement from fathers in existing programs suggests adaptation is needed. This multiphase study examines the feasibility of a synchronous, virtual mind-body intervention adapted for FCYSHCN. Methods: 31 FCYSHCN were recruited online via community partners and recruitment portals in an academic medical center in Boston, MA. Phase 1 consisted of individual interviews (N = 17) to determine fathers' stressors, coping strategies, program needs, and suggested adaptations to the intervention protocol. The Phase 2 single arm pilot feasibility trial (N = 14) consisted of eight weekly 60-minute group sessions delivered virtually. Primary feasibility metrics were attendance (benchmark: mean=6 sessions) and electronic survey completion at baseline and post-intervention. Acceptability was assessed using post-session ratings of program satisfaction (4-point Likert scale; scores ≥3 coded as helpful) and helpfulness (e.g., group structure). Exploratory outcomes included validated measures of stress coping, resiliency, parental stress, depression, anxiety, which were analyzed using paired-samples t-tests (alpha=.05) to generate effect sizes (η2). Results: In Phase 1, FCYSHCN discussed primary stressors (e.g., perceived inadequacy as a father) and multifaceted impacts of these stressors on physical, cognitive, emotional, and social wellbeing. Fathers also described coping strategies deemed helpful (e.g., humor) and unhelpful (e.g., "shutting down" from others). Qualitative findings informed intervention modifications. In Phase 2, most FCYSHCN (79%) attended ≥ 6 intervention sessions (mean=7). Follow-up survey completion was high (86%). Session satisfaction was high, with 7/8 sessions rated as helpful by most fathers. Program components deemed most helpful were the group structure, virtual delivery, exposure to a variety of relaxation and meditation skills, and the length of sessions. Although we were not powered to observe pre-post change, stress coping improved (p = .02, η2 = 0.42) and confidence increased in applying relaxation (p = .04, η2 = 0.34) and assertiveness techniques (p = .05, η2 = 0.31). Conclusions: The first mind-body resiliency program for FCYSHCN is feasible and acceptable. Further testing is warranted in randomized trials with diverse samples of fathers, an appropriate comparison arm, and longitudinal assessments of psychosocial and biobehavioral outcomes.

Outcomes of Women Undergoing Noncardiac Surgery in Veterans Affairs Compared With Non-Veterans Affairs Care Settings.

Importance: Recent legislation facilitates veterans' ability to receive non-Veterans Affairs (VA) surgical care. Although veterans are predominantly male, the number of women receiving care within the VA has nearly doubled to 10% over the past decade and recent data comparing the surgical care of women in VA and non-VA care settings are lacking. Objective: To compare postoperative outcomes among women treated in VA hospitals vs private-sector hospitals. Design, Setting, and Participants: This coarsened exact-matched cohort study across 9 noncardiac specialties in the Veterans Affairs Surgical Quality Improvement Program (VASQIP) and American College of Surgeons National Surgical Quality Improvement Program (NSQIP) took place from January 1, 2016, to December 31, 2019. Multivariable Poisson models with robust standard errors were used to evaluate the association between VA vs private-sector care settings and 30-day mortality. Hospitals participating in American College of Surgeons NSQIP and VASQIP were included. Data analysis was performed in January 2023. Participants included female patients 18 years old or older. Exposures: Surgical care in VA or private-sector hospitals. Main Outcomes and Measures: Postoperative 30-day mortality and failure to rescue (FTR). Results: Among 1 913 033 procedures analyzed, patients in VASQIP were younger (VASQIP: mean age, 49.8 [SD, 13.0] years; NSQIP: mean age, 55.9 [SD, 16.9] years; P < .001) and although most patients in both groups identified as White, there were significantly more Black women in VASQIP compared with NSQIP (29.6% vs 12.7%; P < .001). The mean risk analysis index score was lower in VASQIP (13.9 [SD, 6.4]) compared with NSQIP (16.3 [SD, 7.8]) (P < .001 for both). Patients in the VA were more likely to have a preoperative acute serious condition (2.4% vs 1.8%: P < .001), but cases in NSQIP were more frequently emergent (6.9% vs 2.6%; P < .001). The 30-day mortality, complications, and FTR were 0.2%, 3.2%, and 0.1% in VASQIP (n = 36 762 procedures) as compared with 0.8%, 5.0%, and 0.5% in NSQIP (n = 1 876 271 procedures), respectively (all P < .001). Among 1 763 540 matched women (n = 36 478 procedures in VASQIP; n = 1 727 062 procedures in NSQIP), these rates were 0.3%, 3.7%, and 0.2% in NSQIP and 0.1%, 3.4%, and 0.1% in VASQIP (all P < .01). Relative to private-sector care, VA surgical care was associated with a lower risk of death (adjusted risk ratio [aRR], 0.41; 95% CI, 0.23-0.76). This finding was robust among women undergoing gynecologic surgery, inpatient surgery, and low-physiologic stress procedures. VA surgical care was also associated with lower risk of FTR (aRR, 0.41; 95% CI, 0.18-0.92) for frail or Black women and inpatient and low-physiologic stress procedures. Conclusions and Relevance: Although women comprise the minority of veterans receiving care within the VA, in this study, VA surgical care for women was associated with half the risk of postoperative death and FTR. The VA appears better equipped to meet the unique surgical needs and risk profiles of veterans, regardless of sex and health policy decisions, including funding, should reflect these important outcome differences.

Development and validity evidence for the resident-led large group teaching assessment instrument in the United States: a methodological study.

PURPOSE: Despite educational mandates to assess resident teaching competence, limited instruments with validity evidence exist for this purpose. Existing instruments do not allow faculty to assess resident-led teaching in a large group format or whether teaching was interactive. This study gathers validity evidence on the use of the Resident-led Large Group Teaching Assessment Instrument (Relate), an instrument used by faculty to assess resident teaching competency. Relate comprises 23 behaviors divided into six elements: learning environment, goals and objectives, content of talk, promotion of understanding and retention, session management, and closure. METHODS: Messick's unified validity framework was used for this study. Investigators used video recordings of resident-led teaching from three pediatric residency programs to develop Relate and a rater guidebook. Faculty were trained on instrument use through frame-of-reference training. Resident teaching at all sites was video-recorded during 2018-2019. Two trained faculty raters assessed each video. Descriptive statistics on performance were obtained. Validity evidence sources include: rater training effect (response process), reliability and variability (internal structure), and impact on Milestones assessment (relations to other variables). RESULTS: Forty-eight videos, from 16 residents, were analyzed. Rater training improved inter-rater reliability from 0.04 to 0.64. The Φ-coefficient reliability was 0.50. There was a significant correlation between overall Relate performance and the pediatric teaching Milestone, r = 0.34, P = .019. CONCLUSION: Relate provides validity evidence with sufficient reliability to measure resident-led large-group teaching competence.

Presentation Acuity and Surgical Outcomes for Patients With Health Insurance Living in Highly Deprived Neighborhoods.

Importance: Insurance coverage expansion has been proposed as a solution to improving health disparities, but insurance expansion alone may be insufficient to alleviate care access barriers. Objective: To assess the association of Area Deprivation Index (ADI) with postsurgical textbook outcomes (TO) and presentation acuity for individuals with private insurance or Medicare. Design, Setting, and Participants: This cohort study used data from the National Surgical Quality Improvement Program (2013-2019) merged with electronic health record data from 3 academic health care systems. Data were analyzed from June 2022 to August 2023. Exposure: Living in a neighborhood with an ADI greater than 85. Main Outcomes and Measures: TO, defined as absence of unplanned reoperations, Clavien-Dindo grade 4 complications, mortality, emergency department visits/observation stays, and readmissions, and presentation acuity, defined as having preoperative acute serious conditions (PASC) and urgent or emergent cases. Results: Among a cohort of 29 924 patients, the mean (SD) age was 60.6 (15.6) years; 16 424 (54.9%) were female, and 13 500 (45.1) were male. A total of 14 306 patients had private insurance and 15 618 had Medicare. Patients in highly deprived neighborhoods (5536 patients [18.5%]), with an ADI greater than 85, had lower/worse odds of TO in both the private insurance group (adjusted odds ratio [aOR], 0.87; 95% CI, 0.76-0.99; P = .04) and Medicare group (aOR, 0.90; 95% CI, 0.82-1.00; P = .04) and higher odds of PASC and urgent or emergent cases. The association of ADIs greater than 85 with TO lost significance after adjusting for PASC and urgent/emergent cases. Differences in the probability of TO between the lowest-risk (ADI ≤85, no PASC, and elective surgery) and highest-risk (ADI >85, PASC, and urgent/emergent surgery) scenarios stratified by frailty were highest for very frail patients (Risk Analysis Index ≥40) with differences of 40.2% and 43.1% for those with private insurance and Medicare, respectively. Conclusions and Relevance: This study found that patients living in highly deprived neighborhoods had lower/worse odds of TO and higher presentation acuity despite having private insurance or Medicare. These findings suggest that insurance coverage expansion alone is insufficient to overcome health care disparities, possibly due to persistent barriers to preventive care and other complex causes of health inequities.

The acute effects of cannabis, with and without cannabidiol, on attentional bias to cannabis related cues: a randomised, double-blind, placebo-controlled, cross-over study.

RATIONALE: Attentional bias to drug-related stimuli is hypothesised to contribute towards addiction. However, the acute effects of Δ9-tetrahydrocannabinol (THC) on attentional bias to cannabis cues, the differential response in adults and adolescents, and the moderating effect of cannabidiol (CBD) are unknown. OBJECTIVES: Our study investigated (1) the acute effects of vaporised cannabis on attentional bias to cannabis-related images in adults and adolescents and (2) the moderating influences of age and CBD. METHODS: We conducted a randomised, double-blind, placebo-controlled, cross-over study where three weight-adjusted vaporised cannabis preparations: 'THC' (8 mg THC for a 75-kg person), 'THC + CBD' (8 mg THC and 24 mg CBD for a 75-kg person) and PLA (matched placebo). Cannabis was administered on 3 separate days to 48 participants, who used cannabis 0.5-3 days/week: 24 adolescents (12 females, aged 16-17) and 24 adults (12 females, aged 26-29). Participants completed a visual probe task with cannabis cues. Our primary outcome was attentional bias to cannabis stimuli, measured using the differential reaction time to a cannabis vs. neutral probe, on 200-ms trials. RESULTS: In contrast to hypotheses, attention was directed away from cannabis cues on placebo, and there was a main effect of the drug (F(2,92) = 3.865, p = 0.024, η2p = 0.077), indicating THC administration eliminated this bias. There was no significant impact of CBD nor an age-by-drug interaction. CONCLUSIONS: Acute THC intoxication eliminated attentional bias away from cannabis cues. There was no evidence of differential response in adolescents compared to adults and no evidence that a moderate vaporised dose of CBD altered the impact of cannabis on attentional bias. TRIAL REGISTRATION: This study was listed with the US National Library of Medicine and registered on ClinicalTrials.gov, URL: Do Adolescents and Adults Differ in Their Acute Response to Cannabis?-Full Text View-ClinicalTrials.gov, registration number: NCT04851392.

Association of Frailty with Healthcare Utilization for Patients over One Year Following Surgical Evaluation.

OBJECTIVE: Characterize the distribution of healthcare utilization associated with pre-operative frailty in the year following evaluation by a surgeon. SUMMARY BACKGROUND DATA: Frailty is associated with increased morbidity, mortality, and costs for surgical patients. However, the total financial burden for frail patients beyond the index surgery and inpatient stay remains unknown. METHODS: Prospective cohort assembled from February 2016 to December 2020 within a multi-hospital integrated healthcare delivery and finance system (IDFS), from patients evaluated with the Risk Analysis Index (RAI) of frailty. Inclusion criteria: age greater than 18, valid RAI, membership in the IDFS Health Plan. Data were stratified by frailty and surgical status. RESULTS: The mean (SD) age was 54.7 (16.1) and 58.2% female of the cohort (n=86,572). For all patients with reimbursement for surgery (n=53,856), frail and very frail patients incurred respective increases of 8% ( P =0.027) and 29% ( P <0.001) on utilization relative to the normal group. Robust patients saw a 52% ( P <0.001) decrease. This pattern was more pronounced in the cohort without surgery (n=32,716). The increase over normal utilization for frail and very frail patients increased to 23% ( P =0.004) and 68% ( P <0.001), respectively. Utilization among robust patients decreased 62% ( P <0.001). Increases among the frail were primarily due to increased inpatient medical and post-acute care services (all P <0.001). CONCLUSIONS: Patient frailty is associated with increased total healthcare utilization, primarily via increased inpatient medical and post-acute care following surgery. Quantifying these frailty-related financial burdens may inform clinical decision making as well as the design of value-based reimbursement strategies.