Reliability of a Measure of Admission Intensity for Emergency Physicians.

STUDY OBJECTIVE: We assess the stability of a measure of emergency department (ED) admission intensity for value-based care programs designed to reduce variation in ED admission rates. Measure stability is important to accurately assess admission rates across sites and among physicians. METHODS: We sampled data from 358 EDs in 41 states (January 2018 to December 2021), separate from sites where the measure was derived. The measure is the ED admission rate per 100 ED visits for 16 clinical conditions and 535 included International Classification of Disease 10 diagnosis codes. We used descriptive plots and multilevel linear probability models to assess stability over time across EDs and among physicians. RESULTS: Across included 3,571 ED-quarters, the average admission rate was 27.6% (95% confidence interval [CI] 26.0% to 28.2%). The between-facility standard deviation was 9.7% (95% CI 9.0% to 10.6%), and the within-facility standard deviation was 3.0% (95% CI 2.95% to 3.10%), with an intraclass correlation coefficient of 0.91. At the physician-quarter level, the average admission rate was 28.3% (95% CI 28.0% to 28.5%) among 7,002 physicians. Relative to their site's mean in each quarter, the between-physician standard deviation was 6.7% (95% CI 6.6% to 6.8%), and the within-physician standard deviation was 5.5% (95% CI 5.5% to 5.6%), with an intraclass correlation coefficient of 0.59. Moreover, 2.9% of physicians were high-admitting in 80%+ of their practice quarters relative to their peers in the same ED and in the same quarter, whereas 3.9% were low-admitting. CONCLUSION: The measure exhibits stability in characterizing ED-level admission rates and reliably identifies high- and low-admitting physicians.

Implementation of an emergency department back pain clinical management tool on the early diagnosis and testing of spinal epidural abscess.

BACKGROUND: Spinal epidural abscess (SEA) is a rare, catastrophic condition for which diagnostic delays are common. Our national group develops evidence-based guidelines, known as clinical management tools (CMT), to reduce high-risk misdiagnoses. We study whether implementation of our back pain CMT improved SEA diagnostic timeliness and testing rates in the emergency department (ED). METHODS: We conducted a retrospective observational study before and after implementation of a nontraumatic back pain CMT for SEA in a national group. Outcomes included diagnostic timeliness and test utilization. We used regression analysis to compare differences before (January 2016-June 2017) and after (January 2018-December 2019) with 95% confidence intervals (CIs) clustered by facility. We graphed monthly testing rates. RESULTS: In 59 EDs, pre versus post periods included 141,273 (4.8%) versus 192,244 (4.5%) back pain visits and 188 versus 369 SEA visits, respectively. After implementation, SEA visits with prior related visits were unchanged (12.2% vs. 13.3%, difference +1.0%, 95% CI -4.5% to 6.5%). Mean number of days to diagnosis decreased but not significantly (15.2 days vs. 11.9 days, difference -3.3 days, 95% CI -7.1 to 0.6 days). Back pain visits receiving CT (13.7% vs. 21.1%, difference +7.3%, 95% CI 6.1% to 8.6%) and MRI (2.9% vs. 4.4%, difference +1.4%, 95% CI 1.0% to 1.9%) increased. Spine X-rays decreased (22.6% vs. 20.5%, difference 2.1%, 95% CI -4.3% to 0.1%). Back pain visits receiving erythrocyte sedimentation rate or C-reactive protein increased (1.9% vs. 3.5%, difference +1.6%, 95% CI 1.3% to 1.9%). CONCLUSIONS: Back pain CMT implementation was associated with an increased rate of recommended imaging and laboratory testing in back pain. There was no associated reduction in the proportion of SEA cases with a related prior visit or time to SEA diagnosis.

Development and Internal Validation of an Emergency Department Admission Intensity Measure Using Data From a National Group.

STUDY OBJECTIVE: We develop and assess variation in an emergency department (ED) admission intensity measure intended for value-based payment models. The measure includes ED diagnoses amenable to evidence-based protocols and where admission decisions vary based on physician discretion. METHODS: Measure International Classification of Diseases (ICD)-10 codes were selected by face validity by 3 emergency physicians using expertise and administrative data. Feedback was sought from a separate technical panel. Using data from a national group (2018 to 2019), we assessed measure stability at the physician and facility level by quarter using descriptive plots, multilevel linear probability models, and intraclass correlation coefficients (ICC). RESULTS: A total of 535 ICD-10 measure codes were selected from 23,590 codes. Across 127 EDs, facility-quarter admission rates averaged 26.1% (95% confidence interval [CI] 24.5 to 27.7). Between- and within-facility standard deviations were 9.2 (95% CI 8.2 to 10.5) and 2.9 (95% CI 2.7 to 3.0), respectively, with an ICC of 0.91. Most ED-quarters (749/961) fell within 2.5% of their facility's average. Among 2,398 physicians, quarterly rates averaged 29.1% (95% CI 28.6 to 29.6). The between- and within-physician standard deviation was 6.3 (95% CI 6.1 to 6.5) and 5.3 (95% CI 5.3 to 5.4), respectively, with an ICC of 0.58; 220 physicians (9.2%) had an admission rate consistently higher than average and 193 (8.0%) consistently lower. CONCLUSION: This set of ICD-10 diagnoses demonstrates face validity and stability for quarterly admission rates at the facility and physician levels. The measure may be useful to monitor facility admission rates in value-based models and reliably identify high and low admitters within facilities to manage admission variation.

The microRNA-204-5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction.

BACKGROUND: MicroRNAs regulate cardiac hypertrophy development, which precedes and predicts the risk of heart failure. microRNA-204-5p (miR-204) is well expressed in cardiomyocytes, but its role in developing cardiac hypertrophy and cardiac dysfunction (CH/CD) remains poorly understood. METHODS: We performed RNA-sequencing, echocardiographic, and molecular/morphometric analysis of the heart of mice lacking or overexpressing miR-204 five weeks after trans-aortic constriction (TAC). The neonatal rat cardiomyocytes, H9C2, and HEK293 cells were used to determine the mechanistic role of miR-204. RESULTS: The stretch induces miR-204 expression, and miR-204 inhibits the stretch-induced hypertrophic response of H9C2 cells. The mice lacking miR-204 displayed a higher susceptibility to CH/CD during pressure overload, which was reversed by the adeno-associated virus serotype-9-mediated cardioselective miR-204 overexpression. Bioinformatic analysis of the cardiac transcriptomics of miR-204 knockout mice following pressure overload suggested deregulation of apelin-receptor (APJ) signalling. We found that the stretch-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation and hypertrophy-related genes expression depend on the APJ, and both of these effects are subject to miR-204 levels. The dynamin inhibitor dynasore inhibited both stretch-induced APJ endocytosis and ERK1/2 activation. In contrast, the miR-204-induced APJ endocytosis was neither inhibited by dynamin inhibitors (dynasore and dyngo) nor associated with ERK1/2 activation. We find that the miR-204 increases the expression of ras-associated binding proteins (e.g., Rab5a, Rab7) that regulate cellular endocytosis. CONCLUSIONS: Our results show that miR-204 regulates trafficking of APJ and confers resistance to pressure overload-induced CH/CD, and boosting miR-204 can inhibit the development of CH/CD.

The "NUTS" statistic: Applying an EBM disease model to defensive medicine.

Physicians believe that malpractice concerns result in unnecessary testing, and many emergency physicians state that avoiding malpractice is a contributing factor to ordering medically unnecessary tests. Unfortunately, defensive medicine does not come without possible harm to patients who may be subject to non-beneficial, downstream testing, procedures, and hospitalizations. We submit a novel statistic, "NUTS" or "Number of Unnecessary Tests to avoid one Suit. " We calculated a NUTS of 4737 for troponin testing in ED patients with suspected myocardial infarction, meaning a clinician will need to order 4737 medically unnecessary troponin tests to avoid one missed myocardial infarction lawsuit. The NUTS framework offers us an evidence-based lens to examine defensive medicine less superstitiously and more based on currently available data.

miR-23b and miR-27b are oncogenic microRNAs in breast cancer: evidence from a CRISPR/Cas9 deletion study.

BACKGROUND: Altered expression of microRNAs (miRNAs) is known to contribute to cancer progression. miR-23b and miR-27b, encoded within the same miRNA cluster, are reported to have both tumor suppressive and oncogenic activity across human cancers, including breast cancer. METHODS: To clarify this dichotomous role in breast cancer, miR-23b and miR-27b were knocked out using CRISPR/Cas9 gene knockout technology, and the role of endogenous miR-23b and miR-27b was examined in a breast cancer model system in vitro and in vivo. RESULTS: Characterization of the knockout cells in vitro demonstrated that miR-23b and miR-27b are indeed oncogenic miRNAs in MCF7 breast cancer cells. miR-23b and miR-27b knockout reduced tumor growth in xenograft nude mice fed a standard diet, supporting their oncogenic role in vivo. However, when xenograft mice were provided a fish-oil diet, miR-27b depletion, but not miR-23b depletion, compromised fish-oil-induced suppression of xenograft growth, indicating a context-dependent nature of miR-27b oncogenic activity. CONCLUSIONS: Our results demonstrate that miR-23b and miR-27b are primarily oncogenic in MCF7 breast cancer cells and that miR-27b may have tumor suppressive activity under certain circumstances.

Temperature-Responsive Hydrophobic Silica Nanoparticle Ultrasound Contrast Agents Directed by Phospholipid Phase Behavior.

In this paper, we report ultrasonically active nanoscale contrast agents that behave as thermometric sensors through phase change in their stabilizing phospholipid monolayer. Phospholipid-stabilized, hydrophobic mesoporous silica nanoparticles (P@hMSNs) are known to interact with high-intensity focused ultrasound (HIFU) to promote cavitation at their surfaces, which can be used for both imaging and therapy. We show that the lateral lipid phase behavior of the phosphocholine lipid dictates the acoustic contrast of the P@hMSNs. When the lipids are in the gel phase below their melting temperature, the P@hMSNs generate detectable microbubbles when exposed to HIFU. However, if the lipids exhibit a liquid expanded phase, the P@hMSNs cease to generate bubbles in response to HIFU insonation. We verify that the heating and subsequent transition of lipid coating the hMSN are associated with the loss of acoustic response by doping laurdan dye into the lipid monolayer and imaging lipid phase through red shifts in emission spectra. Similarly, cessation of cavitation was also induced by adding a fluidizing surfactant such as Triton X, which could be reversed upon washing away the excess surfactant. Finally, by controlling for the partial fluidization caused by the adsorption of protein, P@hMSNs may be used as thermometric sensors of the bulk fluid temperature. These findings not only impact the utilization of nanoscale agents as stimulus-responsive ultrasound contrast agents but also have broader implications for how cavitation may be initiated at surfaces coated by a surfactant.

Reduced Myocardial Reserve in Young X-Linked Muscular Dystrophy Mice Diagnosed by Two-Dimensional Strain Analysis Combined with Stress Echocardiography.

BACKGROUND: Early, sensitive, and reproducible evaluation of left ventricular function is imperative for the diagnosis of cardiac dysfunction in patients with Duchene muscular dystrophy. The aim of this study was to test the hypothesis that combining two-dimensional strain analysis with catecholamine stress could be a sensitive method for detecting early cardiac dysfunction. METHODS: Mdx (C57BL/10ScSn-Dmdmdx/J, a mouse model of DMD) and control (C57BL/10ScSn) mice were studied with conventional M-mode and high-frequency ultrasound-based two-dimensional speckle-tracking echocardiography using long- and short-axis images of the left ventricle at baseline and after intraperitoneal isoprenaline (ISO) administration (2 µg/g body weight). RESULTS: Conventional M-mode analysis showed no differences in left ventricular fractional shortening, wall thickness, or internal diameter at diastole between mdx and control mice before the age of 6 months. ISO increased left ventricular ejection fraction and fractional shortening to the same extent in mdx and control mice at young ages (3, 4, and 5 months). No differences in basal peak systolic strain (PSS) but increased SDs of times to PSS between young mdx and control mice were found. After ISO, PSS and percentile changes of PSS were significantly diminished in mdx mice compared with control mice at young ages. ISO increased the normalized maximum difference of times to PSS in young mdx mice but not in young control mice, suggesting that ISO reduces cardiac contractile synchrony in young mdx mice. CONCLUSIONS: This study suggests that catecholamine stress coupled with two-dimensional strain analysis is a feasible and sensitive approach for detecting early onset of cardiac dysfunction, which is instrumental for early diagnosis of cardiac dysfunction and early treatment.

The relationship between race/ethnicity and the perceived experience of mental health care.

Although there is a vast amount of literature on differences in the perceived experiences of general health care among different racial/ethnic groups, few studies have examined the relationship between race/ethnicity and perceptions of mental health care. The purpose of this study was to determine whether non-Hispanic African Americans and Hispanics had more negative (or less positive) perceptions of the mental health treatment they receive compared to non-Hispanic Whites. Data were from the 1998-2006 Florida Health Services Surveys. The findings indicated that African Americans and Hispanics were less likely than Whites to have favorable perceptions of the mental health care services they received, even after adjusting for demographic and health status variables. Interventions should be designed to address disparities in mental health treatment and the perceptions of such treatment. (PsycINFO Database Record