Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Racial Discrimination, Neural Connectivity, and Epigenetic Aging Among Black Women.

Importance: Racial discrimination increases the risk of adverse brain health outcomes, potentially via neuroplastic changes in emotion processing networks. The involvement of deep brain regions (brainstem and midbrain) in these responses is unknown. Potential associations of racial discrimination with alterations in deep brain functional connectivity and accelerated epigenetic aging, a process that substantially increases vulnerability to health problems, are also unknown. Objective: To examine associations of racial discrimination with brainstem and midbrain resting-state functional connectivity (RSFC) and DNA methylation age acceleration (DMAA) among Black women in the US. Design, Setting, and Participants: This cohort study was conducted between January 1, 2012, and February 28, 2015, and included a community-based sample of Black women (aged ≥18 years) recruited as part of the Grady Trauma Project. Self-reported racial discrimination was examined in association with seed-to-voxel brain connectivity, including the locus coeruleus (LC), periaqueductal gray (PAG), and superior colliculus (SC); an index of DMAA (Horvath clock) was also evaluated. Posttraumatic stress disorder (PTSD), trauma exposure, and age were used as covariates in statistical models to isolate racial discrimination-related variance. Data analysis was conducted between January 10 and October 30, 2023. Exposure: Varying levels of racial discrimination exposure, other trauma exposure, and posttraumatic stress disorder (PTSD). Main Outcomes and Measures: Racial discrimination frequency was assessed with the Experiences of Discrimination Scale, other trauma exposure was evaluated with the Traumatic Events Inventory, and current PTSD was evaluated with the PTSD Symptom Scale. Seed-to-voxel functional connectivity analyses were conducted with LC, PAG, and SC seeds. To assess DMAA, the Methylation EPIC BeadChip assay (Illumina) was conducted with whole-blood samples from a subset of 49 participants. Results: This study included 90 Black women, with a mean (SD) age of 38.5 (11.3) years. Greater racial discrimination was associated with greater left LC RSFC to the bilateral precuneus (a region within the default mode network implicated in rumination and reliving of past events; cluster size k = 228; t85 = 4.78; P < .001, false discovery rate-corrected). Significant indirect effects were observed for the left LC-precuneus RSFC on the association between racial discrimination and DMAA (ß [SE] = 0.45 [0.16]; 95% CI, 0.12-0.77). Conclusions and Relevance: In this study, more frequent racial discrimination was associated with proportionately greater RSFC of the LC to the precuneus, and these connectivity alterations were associated with DMAA. These findings suggest that racial discrimination contributes to accelerated biological aging via altered connectivity between the LC and default mode network, increasing vulnerability for brain health problems.

Intravenous Opioid Administration During Mechanical Ventilation and Use After Hospital Discharge.

Importance: Guidelines recommend an analgesia-first strategy for sedation during mechanical ventilation, but associations between opioids provided during mechanical ventilation and posthospitalization opioid-related outcomes are unclear. Objective: To evaluate associations between an intravenous opioid dose received during mechanical ventilation and postdischarge opioid-related outcomes in medical (nonsurgical) patients. Design, Setting, and Participants: This retrospective cohort study evaluated adults receiving mechanical ventilation lasting 24 hours or more for acute respiratory failure and surviving hospitalization. Participants from 21 Kaiser Permanente Northern California hospitals from January 1, 2012, to December 31, 2019, were included. Data were analyzed from October 1, 2020, to October 31, 2023. Exposures: Terciles of median daily intravenous fentanyl equivalents during mechanical ventilation. Main Outcomes and Measures: The primary outcome was the first filled opioid prescription in 1 year after discharge. Secondary outcomes included persistent opioid use and opioid-associated complications. Secondary analyses tested for interaction between opioid doses during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Estimates were based on multivariable-adjusted time-to-event analyses, with death as a competing risk, and censored for hospice or palliative care referral, rehospitalization with receipt of opioid, or loss of Kaiser Permanente plan membership. Results: The study included 6746 patients across 21 hospitals (median age, 67 years [IQR, 57-76 years]; 53.0% male). Of the participants, 3114 (46.2%) filled an opioid prescription in the year prior to admission. The median daily fentanyl equivalent during mechanical ventilation was 200 µg (IQR, 40-1000 µg), with terciles of 0 to 67 µg, more than 67 to 700 µg, and more than 700 µg. Compared with patients who did not receive opioids during mechanical ventilation (n = 1013), a higher daily opioid dose was associated with opioid prescriptions in the year after discharge (n = 2942 outcomes; tercile 1: adjusted hazard ratio [AHR], 1.00 [95% CI, 0.85-1.17], tercile 2: AHR, 1.20 [95% CI, 1.03-1.40], and tercile 3: AHR, 1.25 [95% CI, 1.07-1.47]). Higher doses of opioids during mechanical ventilation were also associated with persistent opioid use after hospitalization (n = 1410 outcomes; tercile 3 vs no opioids: odds ratio, 1.44 [95% CI, 1.14-1.83]). No interaction was observed between opioid dose during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Conclusions and Relevance: In this retrospective cohort study of patients receiving mechanical ventilation, opioids administered during mechanical ventilation were associated with opioid prescriptions following hospital discharge. Additional studies to evaluate risks and benefits of strategies using lower opioid doses are warranted.

Challenges and opportunities of English as the medium of instruction in diploma midwifery programs in Bangladesh: a mixed-methods study.

BACKGROUND: English is generally recognized as the international language of science and most research on evidence-based medicine is produced in English. While Bangla is the dominant language in Bangladesh, public midwifery degree programs use English as the medium of instruction (EMI). This enables faculty and student access to the latest evidence-based midwifery content, which is essential for provision of quality care later. Yet, it also poses a barrier, as limited English mastery among students and faculty limits both teaching and learning. METHODS: This mixed-methods study investigates the challenges and opportunities associated with the implementation of EMI in the context of diploma midwifery education in Bangladesh. Surveys were sent to principals at 38 public midwifery education institutions, and 14 English instructors at those schools. Additionally, ten key informant interviews were held with select knowledgeable stakeholders with key themes identified. RESULTS: Surveys found that English instructors are primarily guest lecturers, trained in general or business English, without a standardized curriculum or functional English language laboratories. Three themes were identified in the key informant interviews. First, in addition to students' challenges with English, faculty mastery of English presented challenges as well. Second, language labs were poorly maintained, often non-functional, and lacked faculty. Third, an alternative education model, such as the English for Specific Purposes (ESP) curriculum,  has potential to strengthen English competencies within midwifery schools. CONCLUSIONS: ESP, which teaches English for application in a specific discipline, is one option available in Bangladesh for midwifery education. Native language instruction and the middle ground of multilingualism are also useful options. Although a major undertaking, investing in an ESP model and translation of technical midwifery content into relevant mother tongues may provide faster and more complete learning. In addition, a tiered system of requirements for English competencies tied to higher levels of midwifery education could build bridges to students to help them access global evidence-based care resources. Higher levels might emphasize English more heavily, while the diploma level would follow a multilingualism approach, teach using an ESP curriculum, and have complementary emphasis on the mother tongue.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Associations of Internal Medicine Residency Milestone Ratings and Certification Examination Scores With Patient Outcomes.

Importance: Despite its importance to medical education and competency assessment for internal medicine trainees, evidence about the relationship between physicians' milestone residency ratings or the American Board of Internal Medicine's initial certification examination and their hospitalized patients' outcomes is sparse. Objective: To examine the association between physicians' milestone ratings and certification examination scores and hospital outcomes for their patients. Design, Setting, and Participants: Retrospective cohort analyses of 6898 hospitalists completing training in 2016 to 2018 and caring for Medicare fee-for-service beneficiaries during hospitalizations in 2017 to 2019 at US hospitals. Main Outcomes and Measures: Primary outcome measures included 7-day mortality and readmission rates. Thirty-day mortality and readmission rates, length of stay, and subspecialist consultation frequency were also assessed. Analyses accounted for hospital fixed effects and adjusted for patient characteristics, physician years of experience, and year. Exposures: Certification examination score quartile and milestone ratings, including an overall core competency rating measure equaling the mean of the end of residency milestone subcompetency ratings categorized as low, medium, or high, and a knowledge core competency measure categorized similarly. Results: Among 455 120 hospitalizations, median patient age was 79 years (IQR, 73-86 years), 56.5% of patients were female, 1.9% were Asian, 9.8% were Black, 4.6% were Hispanic, and 81.9% were White. The 7-day mortality and readmission rates were 3.5% (95% CI, 3.4%-3.6%) and 5.6% (95% CI, 5.5%-5.6%), respectively, and were 8.8% (95% CI, 8.7%-8.9%) and 16.6% (95% CI, 16.5%-16.7%) for mortality and readmission at 30 days. Mean length of stay and number of specialty consultations were 3.6 days (95% CI, 3.6-3.6 days) and 1.01 (95% CI, 1.00-1.03), respectively. A high vs low overall or knowledge milestone core competency rating was associated with none of the outcome measures assessed. For example, a high vs low overall core competency rating was associated with a nonsignificant 2.7% increase in 7-day mortality rates (95% CI, -5.2% to 10.6%; P = .51). In contrast, top vs bottom examination score quartile was associated with a significant 8.0% reduction in 7-day mortality rates (95% CI, -13.0% to -3.1%; P = .002) and a 9.3% reduction in 7-day readmission rates (95% CI, -13.0% to -5.7%; P < .001). For 30-day mortality, this association was -3.5% (95% CI, -6.7% to -0.4%; P = .03). Top vs bottom examination score quartile was associated with 2.4% more consultations (95% CI, 0.8%-3.9%; P < .003) but was not associated with length of stay or 30-day readmission rates. Conclusions and Relevance: Among newly trained hospitalists, certification examination score, but not residency milestone ratings, was associated with improved outcomes among hospitalized Medicare beneficiaries.

Associations Between Organizational Communication and Patients' Experience of Prolonged Emotional Impact Following Medical Errors.

BACKGROUND: The emotional impact of medical errors on patients may be long-lasting. Factors associated with prolonged emotional impacts are poorly understood. METHODS: The authors conducted a subanalysis of a 2017 survey (response rate 36.8% [2,536/6,891]) of US adults to assess emotional impact of medical error. Patients reporting a medical error were included if the error occurred ≥ 1 year prior. Duration of emotional impact was categorized into no/short-term impact (impact lasting < 1 month), prolonged impact (> 1 month), and especially prolonged impact (> 1 year). Based on their reported experience with communication about the error, patients' experience was categorized as consistent with national disclosure guidelines, contrary to guidelines, mixed, or neither. Multinomial regression was used to examine associations between patient factors, event characteristics, and organizational communication with prolonged emotional impact (> 1 month, > 1 year). RESULTS: Of all survey respondents, 17.8% (451/2,536) reported an error occurring ≥ 1 year prior. Of these, 51.2% (231/451) reported prolonged/especially prolonged emotional impact (30.8% prolonged, 20.4% especially prolonged). Factors associated with prolonged emotional impact included female gender (adjusted odds ratio 2.1 [95% confidence interval 1.5-2.9]); low socioeconomic status (SES; 1.7 [1.1-2.7]); physical impact (7.3 [4.3-12.3]); no organizational disclosure and no patient/family error reporting (1.5 [1.03-2.3]); communication contrary to guidelines (4.0 [2.1-7.5]); and mixed communication (2.2 [1.3-3.7]). The same factors were significantly associated with especially prolonged emotional impact (female, 1.7 [1.2-2.5]; low SES, 2.2 [1.3-3.6]; physical impact, 6.8 [3.8-12.5]; no disclosure/reporting, 1.9 [1.2-3.2]; communication contrary to guidelines, 4.6 [2.2-9.4]; mixed communication, 2.1 [1.1-3.9]). CONCLUSION: Prolonged emotional impact affected more than half of Americans self-reporting a medical error. Organizational failure to communicate according to disclosure guidelines after patient-perceived errors may exacerbate harm, particularly for patients at risk of health care disparities.

Sex Differences in Response Inhibition-Related Neural Predictors of Posttraumatic Stress Disorder in Civilians With Recent Trauma.

BACKGROUND: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma. METHODS: Participants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months. RESULTS: Lower response inhibition-related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition-related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus. CONCLUSIONS: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions.

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

This study examines the association between brain dynamic functional network connectivity (dFNC) and current/future posttraumatic stress (PTS) symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.179, pcorrected= 0.021) and future (r=-0.166, pcorrected= 0.029) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.192, pcorrected = 0.021). We additionally observed that the association between the network dynamics of the inter-network brain state with symptom severity is more pronounced in females (r=-0.244, pcorrected = 0.014). Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger protective effect of inter-network brain states against symptom severity in females, underscoring the importance of sex differences.

Association of Major Adverse Financial Events and Later-Stage Cancer Diagnosis in the United States.

PURPOSE: This study assessed the prevalence of specific major adverse financial events (AFEs)-bankruptcies, liens, and evictions-before a cancer diagnosis and their association with later-stage cancer at diagnosis. METHODS: Patients age 20-69 years diagnosed with cancer during 2014-2015 were identified from the Seattle, Louisiana, and Georgia SEER population-based cancer registries. Registry data were linked with LexisNexis consumer data to identify patients with a history of court-documented AFEs before cancer diagnosis. The association of AFEs and later-stage cancer diagnoses (stages III/IV) was assessed using separate sex-specific multivariable logistic regression. RESULTS: Among 101,649 patients with cancer linked to LexisNexis data, 36,791 (36.2%) had a major AFE reported before diagnosis. The mean and median timing of the AFE closest to diagnosis were 93 and 77 months, respectively. AFEs were most common among non-Hispanic Black, unmarried, and low-income patients. Individuals with previous AFEs were more likely to be diagnosed with later-stage cancer than individuals with no AFE (males-odds ratio [OR], 1.09 [95% CI, 1.03 to 1.14]; P < .001; females-OR, 1.18 [95% CI, 1.13 to 1.24]; P < .0001) after adjusting for age, race, marital status, income, registry, and cancer type. Associations between AFEs prediagnosis and later-stage disease did not vary by AFE timing. CONCLUSION: One third of newly diagnosed patients with cancer had a major AFE before their diagnosis. Patients with AFEs were more likely to have later-stage diagnosis, even accounting for traditional measures of socioeconomic status that influence the stage at diagnosis. The prevalence of prediagnosis AFEs underscores financial vulnerability of patients with cancer before their diagnosis, before any subsequent financial burden associated with cancer treatment.

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Differences in Primary Care Follow-up After Acute Care Discharge Within and Across Health Systems: a Retrospective Cohort Study.

BACKGROUND: Timely primary care follow-up after acute care discharge may improve outcomes. OBJECTIVE: To evaluate whether post-discharge follow-up rates differ among patients discharged from hospitals directly affiliated with their primary care clinic (same-site), other hospitals within their health system (same-system), and hospitals outside their health system (outside-system). DESIGN: Retrospective cohort study. PATIENTS: Adult patients of five primary care clinics within a 14-hospital health system who were discharged home after a hospitalization or emergency department (ED) stay. MAIN MEASURES: Primary care visit within 14 days of discharge. A multivariable Poisson regression model was used to estimate adjusted rate ratios (aRRs) and risk differences (aRDs), controlling for sociodemographics, acute visit characteristics, and clinic characteristics. KEY RESULTS: The study included 14,310 discharges (mean age 58.4 [SD 19.0], 59.5% female, 59.5% White, 30.3% Black), of which 57.7% were from the same-site, 14.3% same-system, and 27.9% outside-system. By 14 days, 34.5% of patients discharged from the same-site hospital received primary care follow-up compared to 27.7% of same-system discharges (aRR 0.88, 95% CI 0.79 to 0.98; aRD - 6.5 percentage points (pp), 95% CI - 11.6 to - 1.5) and 20.9% of outside-system discharges (aRR 0.77, 95% CI [0.70 to 0.85]; aRD - 11.9 pp, 95% CI - 16.2 to - 7.7). Differences were greater for hospital discharges than ED discharges (e.g., aRD between same-site and outside-system - 13.5 pp [95% CI, - 20.8 to - 8.3] for hospital discharges and - 10.1 pp [95% CI, - 15.2 to - 5.0] for ED discharges). CONCLUSIONS: Patients discharged from a hospital closely affiliated with their primary care clinic were more likely to receive timely follow-up than those discharged from other hospitals within and outside their health system. Improving care transitions requires coordination across both care settings and health systems.

A Randomized, Sham-Controlled Trial of Cranial Electrical Stimulation for Fibromyalgia Pain and Physical Function, Using Brain Imaging Biomarkers.

Fibromyalgia is a chronic pain syndrome that presents with a constellation of broad symptoms, including decreased physical function, fatigue, cognitive disturbances, and other somatic complaints. Available therapies are often insufficient in treating symptoms, with inadequate pain control commonly leading to opioid usage for attempted management. Cranial electrical stimulation (CES) is a promising non-pharmacologic treatment option for pain conditions that uses pulsed electrical current stimulation to modify brain function via transcutaneous electrodes. These neural mechanisms and the applications of CES in fibromyalgia symptom relief require further exploration. A total of 50 participants from the Atlanta Veterans Affairs Healthcare System (VAHCS) diagnosed with fibromyalgia were enrolled and then block-randomized into either a placebo plus standard therapy or active CES plus standard therapy group. Baseline assessments were obtained prior to the start of treatment. Both interventions occurred over 12 weeks, and participants were assessed at 6 weeks and 12 weeks after treatment initiation. The primary outcome investigated whether pain and functional improvements occur with the application of CES. Additionally, baseline and follow-up resting state functional connectivity magnetic resonance imaging (rs-fcMRI) were obtained at the 6-week and 12-week time points to assess for clinical applications of neural connectivity biomarkers and the underlying neural associations related to treatment effects. This is a randomized, placebo-controlled trial to determine the efficacy of CES for improving pain and function in fibromyalgia and further develop rs-fcMRI as a clinical tool to assess the neural correlates and mechanisms of chronic pain and analgesic response.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Incidence of emergence agitation in children undergoing sevoflurane anesthesia compared to isoflurane anesthesia: An updated systematic review and meta-analysis.

BACKGROUND: Emergence agitation is a complex syndrome of altered consciousness after emergence from anesthesia. It can result in injury to patients and staff and is associated with other postoperative complications. Sevoflurane has been associated with emergence agitation, potentially due to low tissue solubility and therefore speed of emergence. Prior meta-analyses comparing emergence agitation incidence between sevoflurane and isoflurane anesthetics did not demonstrate a statistically significant difference. Given the publication of additional relevant studies not included in prior meta-analyses as well as improved diagnosis of emergence agitation, we aim to perform an updated, comprehensive meta-analysis comparing emergence agitation incidence between sevoflurane and isoflurane anesthetics in children. METHODS: We conducted an updated systematic review and meta-analysis of clinical trials comparing sevoflurane to isoflurane in children <18 years of age, reporting emergence agitation as an outcome, published before July 2023 using databases and registers. Our primary outcome was the incidence of emergence agitation. Secondary outcomes were time to extubation, awakening time, and length of stay in the postanesthetic care unit. We assessed the risk of bias using the Cochrane Risk of Bias tool version 2. We pooled the effect size for the outcomes using the fixed effects model if we had low heterogeneity, otherwise, we used a random-effects model. RESULTS: Eight randomized controlled trials (523 children) were included in the final analysis. The incidence of emergence agitation after isoflurane was significantly lower compared to sevoflurane (risk ratio: 0.62 (95% CI: [0.46-0.83]; I2 = 40.01%, p < .001)). Time to extubation, awakening times, and postanesthetic care unit duration were not significantly different. The protective effect of isoflurane compared to sevoflurane remained significant in subgroups of patients who received premedication or intraoperative systemic analgesics (risk ratios: (0.48 [0.28-0.82]; I2 = 60.78%, p = .01), (0.52 [0.37-0.75]; I2 = 0.00%, p < .001), respectively). CONCLUSION: The risk of emergence agitation in children after maintenance anesthesia with sevoflurane is significantly greater than with isoflurane; we did not find evidence of prolonged emergence or postanesthetic length of stay. When possible, isoflurane should be considered for maintenance anesthesia over sevoflurane in patients at high risk of emergence agitation.

Defining the Time-limited Trial for Patients with Critical Illness: An Official American Thoracic Society Workshop Report.

In critical care, the specific, structured approach to patient care known as a "time-limited trial" has been promoted in the literature to help patients, surrogate decision makers, and clinicians navigate consequential decisions about life-sustaining therapy in the face of uncertainty. Despite promotion of the time-limited trial approach, a lack of consensus about its definition and essential elements prevents optimal clinical use and rigorous evaluation of its impact. The objectives of this American Thoracic Society Workshop Committee were to establish a consensus definition of a time-limited trial in critical care, identify the essential elements for conducting a time-limited trial, and prioritize directions for future work. We achieved these objectives through a structured search of the literature, a modified Delphi process with 100 interdisciplinary and interprofessional stakeholders, and iterative committee discussions. We conclude that a time-limited trial for patients with critical illness is a collaborative plan among clinicians and a patient and/or their surrogate decision makers to use life-sustaining therapy for a defined duration, after which the patient's response to therapy informs the decision to continue care directed toward recovery, transition to care focused exclusively on comfort, or extend the trial's duration. The plan's 16 essential elements follow four sequential phases: consider, plan, support, and reassess. We acknowledge considerable gaps in evidence about the impact of time-limited trials and highlight a concern that if inadequately implemented, time-limited trials may perpetuate unintended harm. Future work is needed to better implement this defined, specific approach to care in practice through a person-centered equity lens and to evaluate its impact on patients, surrogates, and clinicians.

Tapentadol Versus Oxycodone for Opioid-Related Adverse Drug Events and Clinical Outcomes After Inpatient Surgery.

Oxycodone is a commonly prescribed opioid for postoperative pain. However, there has been a marked increase in the use of tapentadol over the previous decade due to a perceived superior safety profile of tapentadol compared to oxycodone. There is limited real-world evidence on the safety of tapentadol compared to oxycodone after surgery. The primary objective was to examine the impact of tapentadol compared to oxycodone use on the incidence of opioid-related adverse drug events after surgery. Data for adult surgical patients receiving tapentadol or oxycodone during hospitalization between January 1, 2018, and December 31, 2021, were collected from electronic medical records of 3 tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events. Patients receiving tapentadol or oxycodone were matched using nearest-neighbour propensity score matching. In the matched cohorts (n = 1,530 vs n = 2,775; mean [standard deviation] age 62.3 [17.0] years vs 61.9 [standard deviation 17.9] years; 43% vs 45% male for the tapentadol vs oxycodone groups, respectively), patients given tapentadol experienced a similar incidence of adverse events overall (14.4%, 220/1,530 vs 12.6%, 349/2,775; P = .100; 95% CI -.35% to 3.95%). Secondary outcomes included an increased risk of delirium (2.7%, 41/1,530 vs 1.3%, 37/2,775), arrhythmias (3.4%, 52/1,530 vs 2.2%, 62/2,775), and length of hospital stay (5 [range 1-201] vs 4 [range 1-226] days) compared with oxycodone use. Further real-world studies are warranted to determine the impact of tapentadol use on a broad range of patient outcomes. PERSPECTIVE: This study provides an early signal that tapentadol use may be associated with an increased risk of some adverse events and a longer length of stay. Further research is needed to examine the impact of tapentadol use on a broad range of patient outcomes in clinical practice settings.

Palliative Intent Treatment and Palliative Care Delivery for Individuals With Advanced Nonsmall Cell Lung Cancer and Melanoma: A Patterns of Care Study.

Introduction: This study aimed to describe the patterns of palliative intent treatment and/or palliative care (PC) delivery among a population-based sample of individuals diagnosed with advanced nonsmall cell lung cancer (NSCLC) or advanced melanoma. Methods: Data from 655 advanced-stage melanoma patients and 2688 advanced-stage NSCLC patients included in the National Cancer Institute's 2017/2018 Patterns of Care study were analyzed. Bivariate and multivariate logistic regression analyses examined factors associated with (1) receipt of PC (including palliative surgery, radiation, and/or systemic therapy after cancer diagnosis, and PC consultations); and (2) timing from diagnosis to receipt of PC. Proportional hazards models also examined factors associated with timing of receipt of PC after diagnosis. Results: A total of 23.5% of those with melanoma and 52.6% of those with NSCLC received some type of PC. For melanoma, stage 4 (vs. stage 3) was associated with higher receipt of PC and receipt within three months of diagnosis. For NSCLC, stage 4 (vs. stage 3) and a diagnosis of depression or psychosocial distress within three months of diagnosis were significantly associated with receipt of PC and receipt within three months of diagnosis. Conclusion: Study findings indicate that those with advanced-stage cancer or who report distress are more likely to receive palliative intent treatment and/or PC. Given that individuals with advanced cancers are living longer and often experience long-lasting symptoms, it is critical to identify and overcome barriers for broadly delivering comprehensive palliative and supportive care.