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.

A significant portion of adolescents suffer from mental illnesses and persistent pain due to repeated stress. The components of the nervous system that link stress and pain in early life remain unclear. Prior studies in adult mice implicated the innate immune system, specifically Toll-like receptors (TLRs), as critical for inducing long-term anxiety and pain-like behaviors in social defeat stress (SDS) models. In this work, we investigated the pain and anxiety behavioral phenotypes of wild-type and TLR4-deficient juvenile mice subjected to repeated SDS and evaluated the engagement of TLR4 by measuring dimerization in the spinal cord, dorsal root ganglia, and prefrontal cortex. Male juvenile (4-week-old) mice (C57BL/6J or Tlr4^-/-) underwent six social defeat sessions with adult aggressor (CD1) mice. In WT mice, SDS promotes chronic mechanical allodynia and thermal hyperalgesia assessed via von Frey testing and the Hargreaves test, respectively. In parallel, the stressed WT mice exhibited transient anxiety-like behavior and long-lasting locomotor activity reduction in the open-field test. Tlr4^-/--stressed animals were resistant to the induction of pain-like behavior but had a remnant of anxious behavior, spending less time in the center of the arena. In WT SDS, there were concordant robust increases in TLR4 dimerization in dorsal root ganglia macrophages and spinal cord microglia, indicating TLR4 activation. These results suggest that the chronic pain phenotype and locomotor impairment induced by SDS in juvenile mice depends on TLR4 engagement evidenced by dimerization in immune cells of the dorsal root ganglia and spinal cord.

BACKGROUND: Nonthermal, pulsed shortwave (radiofrequency) therapy (PSWT) is a nonpharmacologic, noninvasive modality that limited evidence suggests provides analgesia. Its potential favorable risk-benefit ratio stems from its lack of side effects and significant medical risks, applicability to any anatomic location, long treatment duration, and ease of application by simply affixing it with tape. Even with a relatively small treatment effect, PSWT might contribute to a multimodal analgesic regimen, similar to acetaminophen. However, widespread clinical use is hindered by a lack of systematic evidence. The current randomized, controlled pilot study was undertaken to determine the feasibility and optimize the protocol for a subsequent definitive investigation and estimate the treatment effect of PSWT on postoperative pain and opioid consumption. METHODS: Within the recovery room following primary knee and hip arthroplasty, cholecystectomy, hernia repair, and non-mastectomy breast surgery, we applied 1-3 PSWT devices (Model 088, BioElectronics Corporation, Frederick, Maryland) over the surgical bandages. Participants were randomized to 28 days of either active or sham treatment in a double-masked fashion. The outcomes of primary interest were the cumulative opioid consumption and the mean of the average and worst daily pain measured with the Numeric Rating Scale over the first 7 postoperative days. RESULTS: During the first 7 postoperative days, oxycodone consumption in participants given active treatment (n = 55) was a mean (SD) of 21 mg (24) versus 17 mg (26) in patients given sham (n = 57): difference 4 (95% CI, -5 to 13), p = 0.376. During this same period, the average daily pain intensity in patients given active treatment was 2.4 (1.6) versus 2.6 (1.7) in sham: difference -0.2 (95% CI -0.8 to 0.5), p = 0.597. Concurrently, the worst/maximum pain for the active group was 4.6 (2.0) versus 4.7 (2.1) in sham: difference -0.1 (95% CI -0.8 to 0.7), p = 0.888. No device-related systemic side effects or serious adverse events were identified. CONCLUSIONS: Pulsed shortwave (radiofrequency) therapy did not reduce pain scores and opioid requirements to a statistically significant or clinically relevant degree during the initial postoperative week in this pilot study. These results must be replicated with a subsequent study before being considered definitive. Data from this preliminary study may be used to help plan future trials.

Throughout the COVID-19 pandemic, underserved populations, such as racial and ethnic minority communities, were disproportionately impacted by illness and death. Ensuring people from diverse backgrounds have the ability to participate in clinical trials is key to advancing health equity. We sought to analyze the spatial variability in locations of COVID-19 trials sites and to test associations with demographic correlates. All available and searchable COVID-19 studies listed on ClinicalTrials.gov until 04/04/2022 and conducted in the United States were extracted at the trial-level, and locations were geocoded using the Microsoft Bing API. Publicly available demographic data were available at the county level for national analysis and the census tract level for local analysis. Independent variables included eight racial and ethnic covariates, both sexes, and twelve age categories, all of which were population-normalized. The county-level, population-normalized count of study site locations, by type, was used as the outcome for national analysis, thereby enabling the determination of demographic associations with geospatial availability to enroll as a participant in a COVID-19 study. Z-scores of the Getis-Ord Gi statistic were used as the outcome for local analysis in order to account for areas close to those with clinical study sites. For both national (p < 0.001) and local analysis (p = 0.006 for Los Angeles, p = 0.030 for New York), areas with greater proportions of men had significantly fewer studies. Sites were more likely to be found in counties with higher proportions of Asian (p < 0.001) and American Indian or Alaska Native residents (p < 0.001). Areas with greater concentrations of Black or African American residents had significantly lower concentrations of observational (p < 0.001) and government-sponsored COVID-19 studies (p = 0.003) in national analysis and significantly fewer concentrations of study sites in both Los Angeles (p < 0.001) and New York (p = 0.007). Though there appear to be a large number of COVID-19 studies that commenced in the US, they are distributed unevenly, both nationally and locally.

PURPOSE OF REVIEW: Artificial intelligence (AI) offers a new frontier for aiding in the management of both acute and chronic pain, which may potentially transform opioid prescribing practices and addiction prevention strategies. In this review paper, not only do we discuss some of the current literature around predicting various opioid-related outcomes, but we also briefly point out the next steps to improve trustworthiness of these AI models prior to real-time use in clinical workflow. RECENT FINDINGS: Machine learning-based predictive models for identifying risk for persistent postoperative opioid use have been reported for spine surgery, knee arthroplasty, hip arthroplasty, arthroscopic joint surgery, outpatient surgery, and mixed surgical populations. Several machine learning-based models have been described to predict an individuals propensity for opioid use disorder and opioid overdose. Natural language processing and large language model approaches have been described to detect opioid use disorder and persistent postsurgical opioid use from clinical notes. AI holds significant promise in enhancing the management of acute and chronic opioids, which may offer tools to help optimize dosing, predict addiction risks, and personalize pain management strategies. By harnessing the power of AI, healthcare providers can potentially improve patient outcomes, reduce the burden of opioid addiction, and contribute to solving the opioid crisis.

The field of bioelectronic medicine has advanced rapidly from rudimentary electrical therapies to cutting-edge closed-loop systems that integrate real-time physiological monitoring with adaptive neuromodulation. Early innovations, such as cardiac pacemakers and deep brain stimulation, paved the way for these sophisticated technologies. This review traces the historical and technological progression of bioelectronic medicine, culminating in the emerging potential of closed-loop devices for multiple disorders of the brain and body. We emphasize both invasive techniques, such as implantable devices for brain, spinal cord and autonomic regulation, while we introduce new prospects for non-invasive neuromodulation, including focused ultrasound and newly developed autonomic neurography enabling precise detection and titration of inflammatory immune responses. The case for closed-loop non-invasive autonomic neuromodulation (incorporating autonomic neurography and splenic focused ultrasound stimulation) is presented through its applications in conditions such as sepsis and chronic inflammation, illustrating its capacity to revolutionize personalized healthcare. Today, invasive or non-invasive closed-loop systems have yet to be developed that dynamically modulate autonomic nervous system function by responding to real-time physiological and molecular signals; it represents a transformative approach to therapeutic interventions and major opportunity by which the bioelectronic field may advance. Knowledge gaps remain and likely contribute to the lack of available closed loop autonomic neuromodulation systems, namely, (1) significant exogenous and endogenous noise that must be filtered out, (2) potential drift in the signal due to temporal change in disease severity and/or therapy induced neuroplasticity, and (3) confounding effects of exogenous therapies (e.g., concurrent medications that dysregulate autonomic nervous system functions). Leveraging continuous feedback and real-time adjustments may overcome many of these barriers, and these next generation systems have the potential to stand at the forefront of precision medicine, offering new avenues for individualized and adaptive treatment.

BACKGROUND: Percutaneous auricular nerve stimulation (neuromodulation) is an analgesic technique involving the percutaneous implantation of multiple leads at various points on/around the ear followed by the delivery of electric current using an external pulse generator. 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 total knee arthroplasty. METHODS: Within the recovery room following primary, unilateral, total knee arthroplasty, an auricular neuromodulation device (NSS-2 Bridge, Masimo, Irvine, California, USA) was applied using three percutaneous leads and one ground electrode. Participants were randomized to 5 days of either electrical stimulation or sham stimulation in a double-masked fashion. Participants were discharged with the stimulator in situ and removed the disposable devices at home. The dual primary treatment effect outcome measures were the cumulative opioid use (oral oxycodone) and the mean of the average daily pain measured with the Numeric Rating Scale for the first 5 postoperative days. RESULTS: During the first five postoperative days, oxycodone consumption in participants given active stimulation (n=15) was a median (IQR) of 4 mg (2-12) vs 13 mg (5-23) in patients given sham (n=15) treatment (p=0.039). During this same period, the average pain intensity in patients given active stimulation was a median (IQR) of 2.5 (1.5-3.3) vs 4.0 (3.6-4.8) in those given sham (p=0.014). Awakenings due to pain over all eight postoperative nights in participants given active stimulation was a median (IQR) of 5 (3-8) vs 11 (4-14) in those given sham (p<0.001). No device-related localized cutaneous irritation, systemic side effects, or other adverse events were identified. CONCLUSIONS: Percutaneous auricular neuromodulation reduced pain scores and opioid requirements during the initial week after total knee arthroplasty. Given the ease of application as well as the lack of systemic side effects and reported complications, a definitive clinical trial appears warranted. TRIAL REGISTRATION NUMBER: NCT05521516.

BACKGROUND: Traumatic rib fractures are associated with pain lasting weeks to months and a decreased ability to inspire deeply or cough to clear secretions. Ultrasound-guided percutaneous cryoneurolysis involves reversibly ablating peripheral nerve(s) using exceptionally low temperature with a transdermal probe, resulting in a prolonged nerve block with a duration measured in months. We hypothesized that cryoneurolysis would improve analgesia and inspired volume following rib fracture. METHODS: Adults with 1-6 traumatic rib fractures were randomized to either active cryoneurolysis and a sham peripheral nerve block (PNB), or sham cryoneurolysis and active PNB in a participant/observer-masked fashion. The primary endpoint was the maximum inspired volume the day after the procedure as measured with an incentive spirometer. RESULTS: The day after the procedure, the unadjusted median [IQR] maximum inspired volume for participants who received cryoneurolysis (n=11) was 2,250 mL [1,500; 2,500] versus 1,300 mL [750; 2,500] for PNB (n=9, mean difference 496; 95%CI -428 to 1420; t-test P=0.269). When adjusted for covariates (e.g., baseline lung volume), the cryoneurolysis group had an estimated 793 mL greater mean volume than PNB (95%CI 273 to 1,312; ANCOVA P=0.005). Improvement from baseline in maximum inspired volume for cryoneurolysis was 1,000 mL [1,000; 1,375] versus 300 mL [0; 1,000] for PNB (t-test P=0.002). This was equivalent to an improvement over baseline of 100% [90%, 188%] for cryoneurolysis versus 30% [0%, 50%] for PNB (t-test P=0.003). Average daily pain scores were generally lower for the cryoneurolysis group throughout the first month. Total cumulative oxycodone equivalents were 5 mg [0, 13] for cryoneurolysis vs 45 mg [43, 135] for PNB (t-test P=0.013). CONCLUSIONS: Ultrasound-guided percutaneous cryoneurolysis improves maximum inspired lung volume while concurrently decreasing pain and opioid consumption after traumatic rib fracture. These results should be considered preliminary, requiring confirmation with a trial including a larger sample size.