School of Medicine

Introduction: Low tidal-volume ventilation (LTVV), defined as a maximum tidal volume of 8 milliliters per kilogram (mL/kg) of ideal body weight, is a key component of lung protective ventilation. Although emergency department (ED) initiation of LTVV has been associated with improved outcomes, disparities in LTVV application exist. In this study our aim was to evaluate whether rates of LTVV are associated with demographic and physical characteristics in the ED.

Methods: We conducted a retrospective observational cohort study using a dataset of patients who underwent mechanical ventilation at three EDs in two health systems from January 2016–June 2019. Demographic, mechanical ventilation, and outcome data including mortality and hospital-free days were abstracted by automatic query. A LTVV approach was defined as a tidal volume ≤8 mL/kg ideal body weight. We performed descriptive statistics and univariate analysis as indicated, and created a multivariate logistic regression model.

Results: Of 1,029 patients included in the study, 79.5% received LTVV. Tidal volumes of 400-500 mL were used in 81.9% of patients. Approximately 18% of patients had tidal volumes changed in the ED. Female gender (adjusted odds ratio [aOR] 4.17, P< 0.001), obesity (aOR 2.27, P< 0.001), and first-quartile height (aOR 12.2, P < 0.001) were associated with receiving non-LTVV in multivariate regression analysis. Hispanic ethnicity and female gender were associated with first quartile height (68.5%, 43.7%, P < 0.001 for all). Hispanic ethnicity was associated with receiving non-LTVV in univariate analysis (40.8% vs 23.0%, P < 0.001). This relationship did not persist in sensitivity analysis controlling for height, weight, gender, and body mass index. Patients who received LTVV in the ED had 2.1 more hospital-free days compared to those who did not (P = 0.040). No difference in mortality was observed.

Conclusion: Emergency physicians use a narrow range of initial tidal volumes that may not meet lung-protective ventilation goals, with few corrections. Female gender, obesity, and first-quartile height are independently associated with receiving non-LTVV in the ED. Using LTVV in the ED was associated with 2.1 fewer hospital-free days. If confirmed in future studies, these findings have important implications for achieving quality improvement and health equality.

INTRODUCTION:  Diagnostic testing represents a significant portion of healthcare spending, and cost should be considered when ordering such tests.  Needless and excessive spending may occur without an appreciation of the impact on the larger health care system. Knowledge regarding the cost of diagnostic testing among Emergency Medicine residents has not previously been studied.

METHODS: A survey was administered to 20 Emergency Medicine residents from a single ACGME-accredited three-year EM residency program, asking an estimation of the patient charges for 20 commonly ordered laboratory tests and 7 radiological exams. Responses were compared between residency classes to evaluate whether there was a difference based on level of training.

RESULTS: The survey completion rate was 100% (20/20 residents).  Significant discrepancies were noted between the median resident estimates and actual charge to patient for both laboratory and radiological exams.  Nearly all responses were an underestimate of the actual cost. The group median underestimation for laboratory testing was $114, for radiographs $57, and for computed tomography (CT) exams was $1058.   There was statistically significant improvement in accuracy with increasing level of training.

Language is a fundamental aspect of human culture that influences cognitive and perceptual processes. Prior evidence demonstrates personality self-report can vary across multilingual persons' language contexts. We assessed how cultural identification, language dominance, or both dynamically influence bilingual respondents' self-conception, via self-reported personality, across English and Spanish contexts. During separate English and Spanish conditions, 133 Hispanic/Latino bilingual participants (70 female) completed the Big Five Inventory of personality. We used language use and acculturation surveys completed in both languages to calculate participants' relative language dominance and identification with U.S.-American and Hispanic culture. Participants reported higher levels of agreeableness, conscientiousness, and neuroticism in English relative to Spanish. Language dominance predicted cross-language differences in personality report, with higher extraversion reported in participants' dominant language. Within each language, greater endorsement of U.S.-American identity was associated with higher extraversion and conscientiousness and lower reported neuroticism. Agreeableness report in both languages was positively predicted by Hispanic identification. Our results clarify existing literature related to language and cultural effects on personality report among U.S. Hispanics/Latinos. These findings could inform assessments of self-relevant cognitions across languages among bilingual populations and hold relevance for health outcomes affected by cultural processes.

Background

Methods

Results

Conclusions

BACKGROUND: Video games have rapidly become mainstream in recent decades, with over half of the US population involved in some form of digital gaming. However, concerns regarding the potential harms of excessive, disordered gaming have also risen. Internet gaming disorder (IGD) has been proposed as a tentative psychiatric disorder that requires further study by the American Psychological Association (APA) and is recognized as a behavioral addiction by the World Health Organization. Substance use among gamers has also become a concern, with caffeinated or energy drinks and prescription stimulants commonly used for performance enhancement. OBJECTIVE: This study aimed to identify substance use patterns and health-related concerns among gamers among a population of Reddit users. METHODS: We used the public streaming Reddit application programming interface to collect and analyze all posts from the popular subreddit, r/StopGaming. From this corpus of posts, we filtered the dataset for keywords associated with common substances that may be used to enhance gaming performance. We then applied an inductive coding approach to characterize substance use behaviors, gaming genres, and physical and mental health concerns. Potential disordered gaming behavior was also identified using the tentative IGD guidelines proposed by the APA. A chi-square test of independence was used to assess the association between gaming disorder and substance use characteristics, and multivariable logistic regression was used to analyze whether mental health discussion or the mention of any substance with sufficient sample size was significantly associated with IGD. RESULTS: In total, 10,551 posts were collected from Reddit from June 2017 to December 2022. After filtering the dataset for substance-related keywords, 1057 were included for further analysis, of which 286 mentioned both gaming and the use of ≥1 substances. Among the 286 posts that discussed both gaming and substance use, the most mentioned substances were alcohol (n=132), cannabis (n=104), and nicotine (n=48), while the most mentioned genres were role-playing games (n=120), shooters (n=90), and multiplayer online battle arenas (n=43). Self-reported behavior that aligned with the tentative guidelines for IGD was identified in 66.8% (191/286) posts. More than half, 62.9% (180/286) of the posts, discussed a health issue, with the majority (n=144) cited mental health concerns. Common mental health concerns discussed were depression and anxiety. There was a significant association between IGD and substance use (P<.001; chi-square test), and there were significantly increased odds of IGD among those who self-reported substance use (odds ratio 2.29, P<.001) and those who discussed mental health (odds ratio 1.64, P<.03). CONCLUSIONS: As gaming increasingly becomes highly prevalent among various age groups and demographics, a better understanding of the interplay and convergence among disordered gaming, substance use, and negative health impacts can inform the development of interventions to mitigate risks and promote healthier gaming habits.

Converging lines of preclinical and clinical research indicate that females, in stark contrast to males, display an increased prevalence of chronic pain. Females also demonstrate weaker analgesic efficacy in response to opioid therapies when compared with males. These sex-specific differences may be driven by dimorphic endogenous opioidergic responses. In rodent models, analgesia exhibited in males but not females was reversed by inhibiting endogenous opioidergic reception. In humans, the sex-specific endogenous system(s) supporting the direct attenuation of evoked pain has not been identified. To determine whether opioidergic blockade reverses self-regulated analgesia in males as compared to females, the present study combined two operationally analogous clinical trials (n = 98; 51 females and 47 males). In a double-blinded, counterbalanced study involving healthy (n = 39) and chronic low back pain (n = 59) populations, a high-dose naloxone (μ-, κ-, δ-opioid antagonist) vs. placebo-saline cross-over design (15 mg/kg bolus +0.1 mg/kg/h) tested the hypothesis that endogenous opioids mediate analgesia in males but not females. An 11-point visual analog scale (VAS) (0 = no pain; 10 = worst pain imaginable) evaluated pain ratings in response to noxious heat stimulation (49 °C; calf). After baseline pain testing, participants were randomized to a validated four-session mindfulness meditation or sham mindfulness meditation training intervention. Participants practiced their respective meditation during noxious heat, intravenous high-dose naloxone, and placebo saline, respectively. In males and females, meditation significantly lowered evoked pain during saline infusion. Intravenous naloxone inhibited analgesia in males, but pain relief was well preserved in females. The present findings indicate that endogenous opioids mediate self-regulated analgesia in males but not females and underscore the need to establish sex-specific pain therapeutics.

BACKGROUND: Percutaneous auricular nerve stimulation (neuromodulation) involves implanting electrodes around the ear and administering an electric current. A device is currently available within the USA cleared to treat symptoms from opioid withdrawal, and multiple reports suggest a possible postoperative analgesic effect. The current randomized controlled pilot study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent definitive clinical trial; and (2) estimate the treatment effect of auricular neuromodulation on postoperative pain and opioid consumption following two ambulatory surgical procedures. METHODS: Within the recovery room following cholecystectomy or hernia repair, an auricular neuromodulation device (NSS-2 Bridge, Masimo, Irvine, California, USA) was applied. Participants were randomized to 5 days of either electrical stimulation or sham in a double-blinded fashion. RESULTS: In the first 5 days, the median (IQR) pain level for active stimulation (n=15) was 0.6 (0.3-2.4) vs 2.6 (1.1-3.7) for the sham group (n=15) (p=0.041). Concurrently, the median oxycodone use for the active stimulation group was 0 mg (0-1), compared with 0 mg (0-3) for the sham group (p=0.524). Regarding the highest pain level experienced over the entire 8-day study period, only one participant (7%) who received active stimulation experienced severe pain, versus seven (47%) in those given sham (p=0.031). CONCLUSIONS: Percutaneous auricular neuromodulation reduced pain scores but not opioid requirements during the initial week after cholecystectomy and hernia repair. Given the ease of application as well as a lack of systemic side effects and reported complications, a definitive clinical trial appears warranted. TRIAL REGISTRATION NUMBER: NCT05521516.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individuals distinct endophenotype.

BACKGROUND: A bioactive myelin basic protein (MBP) fragment, comprising MBP84-104, is released in sciatic nerve after chronic constriction injury (CCI). Intraneural injection (IN) of MBP84-104 in an intact sciatic nerve is sufficient to induce persistent neuropathic pain-like behavior via robust transcriptional remodeling at the injection site and ipsilateral dorsal root ganglia (DRG) and spinal cord. The sex (female)-specific pronociceptive activity of MBP84-104 associates with sex-specific changes in cholesterol metabolism and activation of estrogen receptor (ESR)1 signaling. METHODS: In male and female normal and post-CCI rat sciatic nerves, we assessed: (i) cholesterol precursor and metabolite levels by lipidomics; (ii) MBP84-104 interactors by mass spectrometry of MBP84-104 pull-down; and (iii) liver X receptor (LXR)α protein expression by immunoblotting. To test the effect of LXRα stimulation on IN MBP84-104-induced mechanical hypersensitivity, the LXRα expression was confirmed along the segmental neuraxis, in DRG and spinal cord, followed by von Frey testing of the effect of intrathecally administered synthetic LXR agonist, GW3965. In cultured male and female rat DRGs exposed to MBP84-104 and/or estrogen treatments, transcriptional effect of LXR stimulation by GW3965 was assessed on downstream cholesterol transporter Abc, interleukin (IL)-6, and pronociceptive Cacna2d1 gene expression. RESULTS: CCI regulated LXRα ligand and receptor levels in nerves of both sexes, with cholesterol precursors, desmosterol and 7-DHC, and oxysterol elevated in females relative to males. MBP84-104 interacted with nuclear receptor coactivator (Ncoa)1, known to activate LXRα, injury-specific in nerves of both sexes. LXR stimulation suppressed ESR1-induced IL-6 and Cacna2d1 expression in cultured DRGs of both sexes and attenuated MBP84-104-induced pain in females. CONCLUSION: The injury-released bioactive MBP fragments induce pronociceptive changes by selective inactivation of nuclear transcription factors, including LXRα. By Ncoa1 sequestration, bioactive MBP fragments render LXRα function to counteract pronociceptive activity of estrogen/ESR1 in sensory neurons. This effect of MBP fragments is prevalent in females due to high circulating estrogen levels in females relative to males. Restoring LXR activity presents a promising therapeutic strategy in management of neuropathic pain induced by bioactive MBP.