Cerebrovascular disease hospitalizations following emergency department headache visits: A nested case-control study.

BACKGROUND: Delayed diagnosis of cerebrovascular disease (CVD) among patients can result in substantial harm. If diagnostic process failures can be identified at emergency department (ED) visits that precede CVD hospitalization, interventions to improve diagnostic accuracy can be developed. METHODS: We conducted a nested case-control study using a cohort of adult ED patients discharged from a single medical center with a benign headache diagnosis from October 1, 2015 to March 31, 2018. Hospitalizations for CVD within 1 year of index ED visit were identified using a regional health information exchange. Patients with subsequent CVD hospitalization (cases) were individually matched to patients without subsequent hospitalization (controls) using patient age and visit date. Demographic, clinical, and ED process characteristics were assessed via detailed chart review. McNemar's test for categorical and paired t-test for continuous variables were used with statistical significance set at ≤0.05. RESULTS: Of the 9157 patients with ED headache visits, 57 (0.6%, 95% confidence interval [CI] = 0.5-0.8) had a subsequent CVD hospitalization. Median time from ED visit to hospitalization was 107 days. In 25 patients (43.9%, 25/57) the CVD hospitalization and the index ED visit were at different hospitals. Fifty-three cases and 53 matched controls were included in the final study analysis. Cases and controls had similar baseline demographic and headache characteristics. Cases more often had a history of stroke (32.1% vs. 13.2%, p = 0.02) and neurosurgery (13.2% vs. 1.9%, p = 0.03) prior to the index ED visit. Cases more often had less than two components of the neurologic examination documented (30.2% vs. 11.3%, p = 0.03). CONCLUSION: We found that 0.6% of patients with an ED headache visit had subsequent CVD hospitalization, often at another medical center. ED visits for headache complaints among patients with prior stroke or neurosurgical procedures may be important opportunities for CVD prevention. Documented neurologic examinations were poorer among cases, which may represent an opportunity for ED process improvement.

Stroke hospitalization after misdiagnosis of "benign dizziness" is lower in specialty care than general practice: a population-based cohort analysis of missed stroke using SPADE methods.

OBJECTIVES: Isolated dizziness is a challenging stroke presentation in the emergency department, but little is known about this problem in other clinical settings. We sought to compare stroke hospitalizations after treat-and-release clinic visits for purportedly "benign dizziness" between general and specialty care settings. METHODS: This was a population-based retrospective cohort study from a national database. We included clinic patients with a first incident treat-and-release visit diagnosis of non-specific dizziness/vertigo or a peripheral vestibular disorder (ICD-9-CM 780.4 or 386.x [not 386.2]). We compared general care (internal medicine, family medicine) vs. specialty care (neurology, otolaryngology) providers. We used propensity scores to control for baseline stroke risk differences unrelated to dizziness diagnosis. We measured excess (observed>expected) stroke hospitalizations in the first 30 d (i.e., missed strokes associated with an adverse event). RESULTS: We analyzed 144,355 patients discharged with "benign dizziness" (n=117,117 diagnosed in general care; n=27,238 in specialty care). After propensity score matching, patients in both groups were at higher risk of stroke in the first 30 d (rate difference per 10,000 treat-and-release visits for "benign dizziness" 24.9 [95% CI 18.6-31.2] in general care and 10.6 [95% CI 6.3-14.9] in specialty care). Short-term stroke risk was higher in general care than specialty care (relative risk, RR 2.2, 95% CI 1.5-3.2) while the long-term risk was not significantly different (RR 1.3, 95% CI 0.9-1.9), indicating higher misdiagnosis-related harms among dizzy patients who initially presented to generalists after adequate propensity matching. CONCLUSIONS: Missed stroke-related harms in general care were roughly twice that in specialty care. Solutions are needed to address this care gap.

Cardioprotective mechanisms of mitochondria-targeted S-nitrosating agent and adenosine triphosphate-sensitive potassium channel opener are mutually exclusive.

Background: Myocytes exposed to stress exhibit significant swelling and reduced contractility. These consequences are ameliorated by adenosine triphosphate-sensitive potassium (KATP) channel opener diazoxide (DZX) via an unknown mechanism. KATP channel openers also provide cardioprotection in multiple animal models. Nitric oxide donors are similarly cardioprotective, and their combination with KATP activation may provide synergistic benefit. We hypothesized that mitochondria-targeted S-nitrosating agent (MitoSNO) would provide synergistic cardioprotection with DZX. Methods: Myocyte volume and contractility were compared following Tyrode's physiologic solution (20 minutes) and stress (hyperkalemic cardioplegia [CPG] ± DZX; n = 5-20 each; 20 minutes) with or without MitoSNO (n = 5-11 each) at the end of stress, followed by Tyrode's solution (20 minutes). Isolated mouse hearts received CPG ± DZX (n = 8-10 each) before global ischemia (90 minutes) with or without MitoSNO (n = 8 each) at the end of ischemia, followed by reperfusion (30 minutes). Left ventricular (LV) pressures were compared using a linear mixed model to assess the impact of treatment on the outcome, adjusting for baseline and balloon volume. Results: Stress (CPG) was associated with reduced myocyte contractility that was prevented by DZX and MitoSNO individually; however, their combination was associated with loss of cardioprotection. Similarly, DZX and MitoSNO improved LV function after prolonged ischemia compared with CPG alone, and cardioprotection was lost with their combination. Conclusions: MitoSNO and DZX provide cardioprotection that is lost with their combination, suggesting mutually exclusive mechanisms of action. The lack of a synergistic beneficial effect informs the current knowledge of the cardioprotective mechanisms of DZX and will aid planning of future clinical trials.

National Trends in Imaging Rates for Eye-Related Emergency Department Visits in the United States.

PURPOSE: To identify nationwide trends and factors associated with advanced imaging (computed tomography [CT] and magnetic resonance imaging [MRI]) use for eye-related emergency department (ED) visits. DESIGN: Retrospective, trend study. METHODS: Setting: National Hospital Ambulatory Medical Care Survey 2007-2015. PATIENT POPULATION: Eye-related ED patients who underwent CT or MRI. MAIN OUTCOME MEASURE(S): Population-based CT/MR imaging rates and independent factors associated with imaging. RESULTS: An estimated 7 million eye-related ED visits occurred between 2007 and 2015. Adjusted for annual eye-related ED visits, the rate of imaging use rose 94%, from 121.7 per 1,000 eye-related ED visits in 2007 to 236.0 per 1,000 eye-related ED visits in 2015. Visual disturbances, contusion of the eye and/or adnexa, open globes and open wounds of ocular adnexa, diplopia, superficial corneal and/or conjunctival injuries, and orbital fractures accounted for 73.2% of all visits where imaging was performed. On multivariable analysis, older patients (odds ratio [OR] = 1.02, 95% confidence interval [CI] 1.01-1.03) and females (OR=2.07, 95% CI 1.18-3.63) were more likely to undergo imaging than younger patients and males. Imaging was also more likely to be performed for Medicare beneficiaries (OR=2.12, 95% CI 1.08-4.15) than for privately insured patients. Patients who were admitted to the hospital were 6 times more likely (OR=6.39, 95% CI 2.04-20.0) to undergo imaging than those who were not admitted. CONCLUSIONS: Advanced imaging for eye-related ED visits has escalated at a higher rate than ED visits for eye complaints. Future studies to develop evidence-based algorithms for use of CT/MR imaging for eye complaints that can help balance benefits against financial costs and health risk are warranted.

Increased Glucose Variability Is Associated With Major Adverse Events After Coronary Artery Bypass.

BACKGROUND: Elevated preoperative hemoglobin A1c (HbA1c) is a predictor of poor outcomes after coronary artery bypass grafting (CABG), but the role of postoperative glucose variability (GV) is unknown. We hypothesized that short-term postoperative GV is associated with major adverse events (MAEs) after isolated CABG. METHODS: This retrospective study evaluated 2215 patients who underwent isolated CABG from January 2012 to March 2018 at 2 medical centers. Postoperative GV in the first 12 hours and 24 hours was measured by the SD, coefficient of variation, and mean amplitude of glycemic excursions. The primary outcome (MAEs) was the composite of postoperative cardiac arrest, pneumonia, renal failure, stroke, sepsis, reoperation, and 30-day mortality. Multivariate logistic regression assessed the independent association of GV with MAE. RESULTS: A total of 2215 patients met the study criteria, and an MAE developed in 260 patients (11.7%). High 12-hour and 24-hour postoperative GV were associated with elevated HbA1c, insulin-dependent diabetes, renal failure, and nonelective operation. Multivariate logistic regression analysis showed MAEs were associated with increased mean postoperative glucose in the first 12 hours (odds ratio [OR], 1.013; 95% confidence interval [CI], 1.008-1.018; P < .001), the first 24 hours (OR, 1.017; 95% CI, 1.010-1.024; P < .001), and 24-hour postoperative GV (OR, 1.22; 95% CI, 1.09-1.37; P < .001). MAEs were not associated with preoperative HbA1c or 12-hour postoperative GV. CONCLUSIONS: Increased 24-hour but not 12-hour postoperative GV after CABG is a predictor of poor outcomes. Preoperative HbA1c is not associated with MAEs after adjusting for postoperative mean glucose and GV.

Model-based clustering for assessing the prognostic value of imaging biomarkers and mixed type tests.

A model-based clustering method is proposed to address two research aims in Alzheimer's disease (AD): to evaluate the accuracy of imaging biomarkers in AD prognosis, and to integrate biomarker information and standard clinical test results into the diagnoses. One challenge in such biomarker studies is that it is often desired or necessary to conduct the evaluation without relying on clinical diagnoses or some other standard references. This is because (1) biomarkers may provide prognostic information long before any standard reference can be acquired; (2) these references are often based on or provide unfair advantage to standard tests. Therefore, they can mask the prognostic value of a useful biomarker, especially when the biomarker is much more accurate than the standard tests. In addition, the biomarkers and existing tests may be of mixed type and vastly different distributions. A model-based clustering method based on finite mixture modeling framework is introduced. The model allows for the inclusion of mixed typed manifest variables with possible differential covariates to evaluate the prognostic value of biomarkers in addition to standard tests without relying on potentially inaccurate reference diagnoses. Maximum likelihood parameter estimation is carried out via the EM algorithm. Accuracy measures and the ROC curves of the biomarkers are derived subsequently. Finally, the method is illustrated with a real example in AD.

nCal: an R package for non-linear calibration.

SUMMARY: Non-linear calibration is a widely used method for quantifying biomarkers wherein concentration-response curves estimated using samples of known concentrations are used to predict the biomarker concentrations in the samples of interest. The R package nCal fills an important gap in the open source, stand-alone software for performing non-linear calibration. For curve fitting, nCal provides a new implementation of a robust, Bayesian hierarchical five-parameter logistic model. nCal supports a simple graphical user interface that can be used by laboratory scientists, and contains functionality for importing data from the multiplex bead array assay instrumentation. AVAILABILITY: The R package 'nCal' is available from http://cran.r-project.org/web/packages/nCal/ under GPL-2 or later.

An open source environment for the statistical evaluation of outbreak detection methods.

We describe the design and initial steps to implementation of a computational framework for evaluating outbreak detection methods. The framework will include components for combining simulated and historical data to create artificial outbreaks and components that implement various outbreak detection algorithms. The first algorithms to be implemented are the three Cumulative Sums (cusum) methods described in the CDC Early Aberration Reporting System.