Measuring the Implementation Preferences of Emergency Medical Services Clinicians Using Discrete Choice Experiments.

INTRODUCTION: Prehospital research and evidence-based guidelines (EBGs) have grown in recent decades, yet there is still a paucity of prehospital implementation research. While recent studies have revealed EMS agency leadership perspectives on implementation, the important perspectives and opinions of frontline EMS clinicians regarding implementation have yet to be explored in a systematic approach. The objective of this study was to measure the preferences of EMS clinicians for the process of EBG implementation and whether current agency practices align with those preferences. METHODS: This study was a cross-sectional survey of National Registry of Emergency Medical Technicians registrants. Eligible participants were certified paramedics who were actively practicing EMS clinicians. The survey contained discrete choice experiments (DCEs) for three EBG implementation scenarios and questions about rank order preferences for various aspects of the implementation process. For the DCEs, we used multinomial logistic regression to analyze the implementation preference choices of EMS clinicians, and latent class analysis to classify respondents into groups by their preferences. RESULTS: A total of 183 respondents completed the survey. Respondents had a median age of 39 years, were 74.9% male, 89.6% White, and 93.4% of non-Hispanic ethnicity. For all three DCE scenarios, respondents were significantly more likely to choose options with hospital feedback and individual-level feedback from EMS agencies. Respondents were significantly less likely to choose options with email/online only education, no feedback from hospitals, and no EMS agency feedback to clinicians. In general, respondents' preferences favored classroom-based training over in-person simulation. For all DCE questions, most respondents (66.2%-77.1%) preferred their survey DCE choice to their agency's current implementation practices. In the rank order preferences, most participants selected "knowledge of the underlying evidence behind the change" as the most important component of the process of implementation. CONCLUSIONS: In this study of EMS clinicians' implementation preferences using DCEs, respondents preferred in-person education, feedback on hospital outcomes, and feedback on their individual performance. However, current practice at EMS agencies rarely matched those expressed EMS clinician preferences. Collectively, these results present opportunities for improving EMS implementation from the EMS clinician perspective.

Tailored Approach to Evaluation and Management of Early Onset Neonatal Sepsis in a Safety-Net Teaching Hospital in Northeast Florida.

Objective Early onset neonatal sepsis (EONS) remains a significant cause of morbidity and mortality in newborns in the immediate postnatal period. High empiric antibiotic use in well-appearing infants with known risk factors for sepsis led the American Academy of Pediatrics (AAP) to revise its 2010 guidelines for the evaluation and management of EONS to avoid overuse of antibiotics. In this recent clinical report, the AAP provided a framework that outlined several evidence-based approaches for sepsis risk assessment in newborns that can be adopted by institutions based on local resources and structure. One of these approaches, the sepsis risk calculator (SRC) developed by Kaiser Permanente, has been widely validated for reducing unnecessary antibiotic exposure and blood work in infants suspected of having EONS. In order to determine the utility and safety of modifying our institution's protocol to the SRC, we implemented a two-phased approach to evaluate the use of SRC in our newborn nursery. Phase 1 utilized a retrospective review of cases with SRC superimposition. If results from Phase 1 were found to be favorable, Phase 2 initiated a trial of the SRC for a six-month period prior to complete implementation. Methods Phase 1 consisted of retrospectively applying the SRC to electronic medical records (EMR) of infants ≥ 35 weeks' gestational age admitted to the newborn nursery with risk factors for EONS between June 2016 and May 2017. We compared actual antibiotic use as determined by the unit's EONS protocol for evaluation and management based on 2010 Centers for Disease Control and Prevention (CDC) and AAP guidelines to SRC-recommended antibiotic use. We used EMR to determine maternal and infant data, blood work results, and antibiotic usage as well as used daily progress notes by the clinical team to determine the clinical status of the infants retrospectively. Based on the projected reduction in blood work and antibiotics use with the retrospective superimposition of SRC on this cohort of infants and identification of our high-risk patient subset, we developed a novel, hybrid EONS protocol that we implemented and assessed throughout Phase 2, a six-month period from August 2018 to January 2019, as a prospective observational study. Results Phase 1 (SRC superimposition) demonstrated that the use of the SRC would have reduced empiric antibiotic use from 56% to 13% in the study cohort when compared with 2010 CDC/AAP guidelines. However, these same findings revealed use of the SRC would have resulted in delayed evaluation and initiation of antibiotics in 2 of 4 chorioamnionitis-exposed infants with positive blood cultures. During Phase 2 (n=302), with the implementation of our tailored approach (SRC implementation with additional blood culture in chorioamnionitis-exposed infants), 12 (4%) neonates received empiric antibiotic treatment compared to nine (3%) neonates who would have been treated per strict adherence to SRC recommendations. No neonate had culture-positive EONS. Continued use of 2010 CDC/AAP guidelines would have led to empiric antibiotic use in 38 (12.6%) infants in this cohort. Conclusion We developed a novel hybrid approach to the evaluation and management of neonates at increased risk of EONS by tailoring SRC recommendations to our safety-net population. Our stewardship effort achieved a safe and significant reduction in antibiotic usage compared to prior usage determined using CDC/AAP guidelines.

A pilot study to identify pharmacogenomic and clinical risk factors associated with opioid related falls and adverse effects in older adults.

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid-related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects. This was an observational study of 44 participants discharged home from the emergency department with an opioid prescription for acute pain and followed for 30 days. We found pain interference may predict opioid-related falls or serious adverse effects within older, opioid-treated patients. If validated, pain interference may prove to be a beneficial marker for risk stratification of older adults initiated on opioids for acute pain.

Association of air pollution with postmenopausal breast cancer risk in UK Biobank.

BACKGROUND: We investigated the association of several air pollution measures with postmenopausal breast cancer (BCa) risk. METHODS: This study included 155,235 postmenopausal women (of which 6146 with BCa) from UK Biobank. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Annual exposure averages were available from 2005, 2006, 2007, and 2010 for NO2, from 2007 and 2010 for PM10, and from 2010 for PM2.5, NOX, PM2.5-10 and PM2.5 absorbance. Information on BCa risk factors was collected at baseline. Cox proportional hazards regression was used to evaluate the associations of year-specific and cumulative average exposures with BCa risk, overall and with 2-year exposure lag, while adjusting for BCa risk factors. RESULTS: PM10 in 2007 and cumulative average PM10 were positively associated with BCa risk (2007 PM10: Hazard ratio [HR] per 10 µg/m3 = 1.18, 95% CI 1.08, 1.29; cumulative average PM10: HR per 10 µg/m3 = 1.99, 95% CI 1.75, 2.27). Compared to women with low exposure, women with higher 2007 PM10 and cumulative average PM10 had greater BCa risk (4th vs. 1st quartile HR = 1.15, 95% CI 1.07, 1.24, p-trend = 0.001 and HR = 1.35, 95% CI 1.25, 1.44, p-trend < 0.0001, respectively). No significant associations were found for any other exposure measures. In the analysis with 2-year exposure lag, both 2007 PM 10 and cumulative average PM10 were positively associated with BCa risk (4th vs. 1st quartile HR = 1.19, 95% CI 1.10, 1.28 and HR = 1.29, 95% CI 1.19, 1.39, respectively). CONCLUSION: Our findings suggest a positive association of 2007 PM10 and cumulative average PM10 with postmenopausal BCa risk.

Association of Early Serum Phosphate Levels and Mortality in Patients with Sepsis.

BACKGROUND: Metabolic derangements in sepsis influence phosphate levels, which may predict mortality outcomes. We investigated the association between initial phosphate levels and 28-day mortality in patients with sepsis. METHODS: We conducted a retrospective analysis of patients with sepsis. Initial (first 24 hours) phosphate levels were divided into phosphate quartile groups for comparisons. We used repeated-measures mixed-models to assess differences in 28-day mortality across the phosphate groups, adjusting for other predictors identified by the Least Absolute Shrinkage and Selection Operator variable selection technique. RESULTS: A total of 1,855 patients were included with 13% overall 28-day mortality (n=237). The highest phosphate quartile (>4.0 milligrams per deciliter [mg/dL]) had a higher mortality rate (28%) than the three lower quartiles (P<0.001). After adjustment (age, organ failure, vasopressor administration, liver disease), the highest initial phosphate was associated with increased odds of 28-day mortality. Patients in the highest phosphate quartile had 2.4 times higher odds of death than the lowest (≤2.6 mg/dL) quartile (P<0.01), 2.6 times higher than the second (2.6-3.2 mg/dL) quartile (P<0.01), and 2.0 times higher than the third (3.2-4.0 mg/dL) quartile (P=0.04). CONCLUSION: Septic patients with the highest phosphate levels had increased odds of mortality. Hyperphosphatemia may be an early indicator of disease severity and risk of adverse outcomes from sepsis.

Factors associated with bleeding after ultrasound-assisted catheter-directed thrombolysis for the treatment of pulmonary embolism.

Ultrasound-assisted catheter directed thrombolysis (US-CDT) is frequently used for the treatment of pulmonary embolism. Due to the variety of thrombolytic and anticoagulant dosing utilized in practice, patients with pulmonary embolism who undergo US-CDT may be at an increased risk of bleeding. The primary objective of this study was to determine factors associated with major bleeding occurring with US-CDT. Secondary outcomes included in-hospital mortality and ventilator-free days. This multicentre retrospective cohort study evaluated inpatients diagnosed with pulmonary embolism and treated with US-CDT and systemic anticoagulation. A total of 173 patients were included. Most patients receiving US-CDT had a submassive pulmonary embolism with a median Pulmonary Embolism Severity Index (PESI) score of 85. Major bleeding events occurred in 37 of the 173 patients (21%). In-hospital mortality occurred in four (11%) of the patients who experienced major bleeding and three (2%) patients who did not experience major bleeding (P = 0.04). Factors associated with a higher risk of major bleeding included female sex and anticoagulation strategy. The odds of major bleeding were 3.3 times higher for women than for men (odds ratio = 3.32, 95% confidence interval 1.29-8.54). In addition, for each second increase in goal aPTT the odds of major bleeding increased by 5% (odds ratio = 1.05, 95% confidence interval 1.02-1.09). In patients with pulmonary embolism treated with US-CDT, major bleeding may be underestimated. In this analysis, major bleeding was associated with female sex and higher goal aPTT levels. In addition, bleeding with US-CDT was associated with a higher risk of in-hospital mortality.

Characterizing OPRM1 DNA methylation in prescription opioid users with chronic musculoskeletal pain.

Introduction: Many patients with chronic pain use prescription opioids. Epigenetic modification of the µ-opioid receptor 1 (OPRM1) gene, which codes for the target protein of opioids, may influence vulnerability to opioid abuse and response to opioid pharmacotherapy, potentially affecting pain outcomes. Objective: Our objective was to investigate associations of clinical and sociodemographic factors with OPRM1 DNA methylation in patients with chronic musculoskeletal pain on long-term prescription opioids. Methods: Sociodemographic variables, survey data (Rapid Estimate of Adult Health Literacy in Medicine-Short Form, Functional Comorbidity Index [FCI], PROMIS 43v2.1 Profile, Opioid Risk Tool, and PROMIS Prescription Pain Medication Misuse), and saliva samples were collected. The genomic DNA extracted from saliva samples were bisulfite converted, amplified by polymerase chain reaction, and processed for OPRM1-targeted DNA methylation analysis on a Pyrosequencing instrument (Qiagen Inc, Valencia, CA). General linear models were used to examine the relationships between the predictors and OPRM1 DNA methylation. Results: Data from 112 patients were analyzed. The best-fitted multivariable model indicated, compared with their counterparts, patients with > eighth grade reading level, degenerative disk disease, substance abuse comorbidity, and opioid use < 1 year (compared with >5 years), had average methylation levels that were 7.7% (95% confidence interval [CI] 0.95%, 14.4%), 11.7% (95% CI 2.7%, 21.1%), 21.7% (95% CI 10.7%, 32.5%), and 16.1% (95% CI 3.3%, 28.8%) higher than the reference groups, respectively. Methylation levels were 2.2% (95% CI 0.64%, 3.7%) lower for every 1 unit increase in FCI and greater by 0.45% (95% CI 0.08%, 0.82%) for every fatigue T score unit increase. Conclusions: OPRM1 methylation levels varied by several patient factors. Further studies are warranted to replicate these findings and determine potential clinical utility.

Comparative study of different SES neighborhood clinics for health literacy and internet access.

Background: As healthcare services are increasingly dependent on patient utilization of technology to effectively deliver services, the digital divide has the potential to exacerbate health disparities if health literacy and internet access present formidable barriers to patient use of technology. Methods: We examined the differences in health literacy and internet access between lower and upper SES neighborhood primary-care clinics in Northeast Florida. The REALM-SF for health literacy was used to assess health literacy and census survey questions were used to assess internet and technology access, during the Fall, 2020. The clinics were affiliated with a safety-net hospital in a major city in Southeastern U.S. Results: Analysis of key demographic data confirmed that the responding patients from economically disadvantaged neighborhood clinics resided in economically disadvantaged zip codes (307 responding patients lived in lower SES neighborhoods) and did have lower education levels (3% of the patients from Upper SES clinics had 11 grade or lower education, compared to 21%-29% of patients from Lower SES clinics). Patient health literacy significantly differed between clinics located in economically disadvantaged neighborhoods and clinics located in more affluent neighborhoods, with Upper SES clinics being 2.4 times more likely to have 9th grade or higher reading level. Access to internet technology was also higher in the Upper SES clinics, with 59% of respondents from Upper SES clinics versus 32%-40% from Lower SES clinics owning a computer or an IPAD. Conclusion: Results of this study have important implications for patient-engaged use of digital technology for health. Healthcare and public health clinics should be aware of the difference in health literacy and internet access when implementing technology-based services, so that advances in medicine, including precision medicine and telehealth, can be disseminated and implemented with broad populations, including disadvantaged groups.

The Frequency of V122I Transthyretin Mutation in a Cohort of African American Individuals With Bilateral Carpal Tunnel Syndrome.

Introduction: Hereditary transthyretin amyloidosis (hATTR) can cause multisystem organ disorders including polyneuropathy and cardiomyopathy. Amongst the many known pathologic mutations of the transthyretin (TTR) gene, the Val122Ile (V122I) mutation can be found in 3-4% of African Americans. Up to 47% of patients with the V122I hATTR cardiomyopathy had a history of carpal tunnel syndrome (CTS). This raises the question should we screen for this mutation in African Americans with bilateral CTS for the purpose of preventing advanced disease associated with hATTR. This is a prospective pilot study to determine the likelihood of African Americans with bilateral CTS having the V122I mutation and whether various clinical factors contribute to that probability. Methodology: Adult African American patients without prior history of amyloidosis diagnosed with bilateral CTS were recruited for the study. They received genetic testing to screen for a TTR mutation. They also completed questionnaires to screen for symptoms of cardiomyopathy and neuropathy, other risk factors for CTS, and family history of CTS and cardiomyopathy. Result: Two of the sixteen patients (12.5%) in this cohort were found to have the V122I mutation. The absence of polyneuropathy and cardiomyopathy symptoms, presence of other CTS risk factors, and absence of family history of CTS and cardiomyopathy did not decrease the likelihood of V122I mutation in this cohort. Conclusion: The frequency of V122I transthyretin mutation in African Americans with bilateral CTS may be higher than 3-4%. The presence of bilateral CTS alone may be a justification to screen for TTR mutation in this population.

Toward realization of remote controlled telecytopathology-a validation study from a large academic medical center from the southeast United States.

INTRODUCTION: With increase in the number and types of biopsies requiring rapid on-site evaluation for adequacy, telecytopathology is one of the solutions. MATERIALS AND METHODS: Using a microscope camera with MS Surface Pro, a live telecytopathology audio video feed for the adequacy of 55 study set validation cases was sent over Zoom from the satellite hospital over 10 miles away with cytopathologists at the main hospital. The study set cases included Diff-Quik-stained smears and core imprints. RESULTS: The overall percent of positive agreement (accuracy) for adequacy during rapid on-site evaluation via telecytopathology was 96%. Core imprint percentage for positive agreement was slightly higher (96.2%), than fine-needle aspiration smears (95.8%). CONCLUSIONS: Use of telecytopathology is the best solution for optimizing the cytopathologist's time for evaluating biopsy adequacy from distant sites.

Effect of desmopressin acetate on acute spontaneous intracranial hemorrhage in patients on antiplatelet therapy.

PURPOSE: To evaluate the impact of desmopressin acetate (DDAVP) on poor outcomes, hematoma expansion, and adverse events in patients diagnosed with a non-traumatic, antiplatelet-associated intracranial hemorrhage (ICH). METHODS: This was a multicenter, retrospective, propensity-matched cohort study comparing DDAVP to control in patients diagnosed with a non-traumatic ICH previously on antiplatelet therapy. Notable exclusion criteria included admission to trauma service, subarachnoid hemorrhages, confounding coagulopathic factors, and hematoma evacuation. Poor outcome, defined as discharge to hospice or in-patient mortality, was the primary outcome. Secondary outcomes included intracranial hematoma expansion and occurrence of adverse events, which included hyponatremia and thromboembolic events. RESULTS: A total of 49 patients receiving DDAVP were compared to 107 controls in the unmatched cohort. Thirty-seven patients treated with DDAVP and 55 controls were included in the propensity-matched analysis, which was adjusted for age, ethnicity, history of diabetes, receipt of platelet transfusion, and thromboembolism prophylaxis. Poor outcome (16.2% DDAVP vs 29% control, p = 0.13), rates of hematoma expansion (11.8% DDAVP vs 11.1% control, p = 0.99), and adverse events (21.6% DDAVP vs 20% control, p = 0.99) were statistically similar between the matched groups. CONCLUSIONS: DDAVP administration in patients with spontaneous antiplatelet-associated ICH was not associated with a reduction in poor outcomes, hematoma expansion, or an increase in adverse events. Use of DDAVP in this patient population appears to be safe. Larger prospective studies are warranted to evaluate DDAVP utility in this patient population.

PICC versus midlines: Comparison of peripherally inserted central catheters and midline catheters with respect to incidence of thromboembolic and infectious complications.

INTRODUCTION: To decrease the complications related to central catheters there has been an increasing utilization of peripherally inserted central catheters (PICC) and ultrasound-guided long peripheral intravenous catheters (i.e. midlines). While the complications of PICC lines are well described there is less reported data on complications related to midline catheters. Our study aims are to compare the incidences of infectious and deep venous thrombosis (DVT) and sepsis related to PICCs and Midlines. METHODS: We performed a single-center retrospective review at an academic hospital. Data were collected on patients admitted between 1/1/2014-5/31/2016. Patient demographics, hospital length of stay (LOS), and ventilator days were collected. Outcomes of interest were line-related infections and thromboembolic events after the placement of these catheters. Endpoints were compared between three groups (PICC group, midline group and PICC placement followed by midline placement group). Univariate and multivariable analyses were used to compare across the three groups. RESULTS: The study included 3560 unique patients with 5058 catheters. There was an increase in use of midlines over the observed study period (245% increase from the end of 2015 to the middle of 2016). We found no significant differences in the rates of DVT among the three groups (PICC 4%, midline 3% and PICC-midline 4%; p = 0.12). There were no differences across the groups for sepsis (PICC 29%, midline 27%, and PICC-midline 32%; p = 0.14) or septic shock (PICC 7%, midline 8%, and PICC-midline 6%; p = 0.39). Adjusted means LOS were higher for patients with PICC lines compared to midlines, in both females and males. PICC group stayed longer, on average, on the ventilator compared to the midline group. No other significant differences were seen among groups. CONCLUSION: Increased utilization of midline catheters were not associated with decreased risk of DVT or sepsis when compared to peripherally inserted central catheters.

Effectiveness of Dual Medication Therapy (Oral Acetaminophen and Oral Ibuprofen) for the Management of Patent Ductus Arteriosus in Extremely Premature Infants: A Feasibility Trial.

OBJECTIVE: The study aimed to evaluate the efficacy of dual medication therapy (DMT) with oral acetaminophen and oral ibuprofen for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA). STUDY DESIGN: In a prospective case-control cohort study (July 2017-May 2019), infants <29 weeks' gestational age and birth weight <1,000 g at ≤14 postnatal days with hsPDA and ratio of the smallest ductal diameter to the ostium of the left pulmonary artery diameter >0.5 were eligible. Infants received 10 mg/kg oral ibuprofen followed by two additional doses of 5 mg/kg at 24 and 48 hours after the initial ibuprofen dose and concomitant treatment with 15 mg/kg oral acetaminophen every 6 hours for 3 days (12 doses). Success of PDA treatment was defined as a small or absent PDA as ascertained by echocardiographic measurements. The p-values of comparisons were adjusted for multiple comparisons to preserve an error rate of 5%. RESULTS: Overall, 20 infants received oral DMT and 11 infants received intravenous single medication therapy (SMT) with ibuprofen. The rates of successful PDA treatment following the first treatment in DMT and SMT groups were not statistically different (11/20 [55%] vs. 4/11 [36%], p = 0.46). However, DMT significantly decreased PDA size (mean difference = 0.54 mm, 95% confidence interval [CI]: 0.21-0.96, adjusted p-value = 0.0002) and PDA/LPA ratio (mean difference = 0.27, 95% CI: 0.10-0.47, adjusted p-value = 0.0004). We observed no evidence of hematologic, hepatic, or renal impairment. CONCLUSION: DMT achieved a greater degree of PDA closure than SMT and did not result in abnormalities in hepatic and renal profile. KEY POINTS: · No consensus on optimal medication for PDA treatment is available.. · Dual oral medication therapy (ibuprofen and acetaminophen) could be an effective alternative treatment for PDA.. · Dual oral medication therapy (ibuprofen and acetaminophen) may have a better safety profile than currently approved medications such as intravenous indomethacin and intravenous ibuprofen..

Associations of Oral Contraceptives with Mammographic Breast Density in Premenopausal Women.

BACKGROUND: We investigated the associations of oral contraceptives (OC) with percent breast density (PD), absolute dense area (DA), nondense area (NDA), and a novel image intensity variation (V) measure in premenopausal women. METHODS: This study included 1,233 controls from a nested case-control study within Nurses' Health Study II cohort. Information on OCs was collected in 1989 and updated biennially. OC use was defined from the questionnaire closest to the mammogram date. PD, DA, and NDA were measured from digitized film mammograms using a computer-assisted thresholding technique; the V measure was obtained with a previously developed algorithm measuring the SD of pixel values in the eroded breast region. Generalized linear regression was used to assess associations between OCs and density measures (square root-transformed PD, DA, and NDA, and -untransformed V). RESULTS: OC use was not associated with PD [current vs. never: ß = -0.06; 95% confidence interval (CI), -0.37-0.24; past vs. never: ß = 0.10; 95% CI, -0.09-0.29], DA (current vs. never: ß = -0.20; 95% CI -0.59-0.18; past vs. never: ß = 0.13; 95% CI, -0.12-0.39), and NDA (current vs. never: ß = -0.19; 95% CI, -0.56-0.18; past vs. never: ß = -0.01; 95% CI, -0.28-0.25). Women with younger age at initiation had significantly greater V-measure (<20 years vs. never: ß = 26.88; 95% CI, 3.18-50.58; 20-24 years vs. never: ß = 20.23; 95% CI, -4.24-44.71; 25-29 years vs. never: ß = 2.61; 95% CI -29.00-34.23; ≥30 years vs. never: ß = 0.28; 95% CI, -34.16-34.72, P trend = 0.03). CONCLUSIONS: Our findings suggest that an earlier age at first OC use was associated with significantly greater V. IMPACT: These findings could guide decisions about the age for OC initiation.

A hypolipoprotein sepsis phenotype indicates reduced lipoprotein antioxidant capacity, increased endothelial dysfunction and organ failure, and worse clinical outcomes.

OBJECTIVE: Approximately one-third of sepsis patients experience poor outcomes including chronic critical illness (CCI, intensive care unit (ICU) stay > 14 days) or early death (in-hospital death within 14 days). We sought to characterize lipoprotein predictive ability for poor outcomes and contribution to sepsis heterogeneity. DESIGN: Prospective cohort study with independent replication cohort. SETTING: Emergency department and surgical ICU at two hospitals. PATIENTS: Sepsis patients presenting within 24 h. METHODS: Measures included cholesterol levels (total cholesterol, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C]), triglycerides, paraoxonase-1 (PON-1), and apolipoprotein A-I (Apo A-I) in the first 24 h. Inflammatory and endothelial markers, and sequential organ failure assessment (SOFA) scores were also measured. LASSO selection assessed predictive ability for outcomes. Unsupervised clustering was used to investigate the contribution of lipid variation to sepsis heterogeneity. MEASUREMENTS AND MAIN RESULTS: 172 patients were enrolled. Most (~ 67%, 114/172) rapidly recovered, while ~ 23% (41/172) developed CCI, and ~ 10% (17/172) had early death. ApoA-I, LDL-C, mechanical ventilation, vasopressor use, and Charlson Comorbidity Score were significant predictors of CCI/early death in LASSO models. Unsupervised clustering yielded two discernible phenotypes. The Hypolipoprotein phenotype was characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1), higher SOFA scores, and worse clinical outcomes (45% rapid recovery, 40% CCI, 16% early death; 28-day mortality, 21%). The Normolipoprotein cluster patients had higher cholesterol levels, less endothelial dysfunction, lower SOFA scores and better outcomes (79% rapid recovery, 15% CCI, 6% early death; 28-day mortality, 15%). Phenotypes were validated in an independent replication cohort (N = 86) with greater sepsis severity, which similarly demonstrated lower HDL-C, ApoA-I, and higher ICAM-1 in the Hypolipoprotein cluster and worse outcomes (46% rapid recovery, 23% CCI, 31% early death; 28-day mortality, 42%). Normolipoprotein patients in the replication cohort had better outcomes (55% rapid recovery, 32% CCI, 13% early death; 28-day mortality, 28%) Top features for cluster discrimination were HDL-C, ApoA-I, total SOFA score, total cholesterol level, and ICAM-1. CONCLUSIONS: Lipoproteins predicted poor sepsis outcomes. A Hypolipoprotein sepsis phenotype was identified and characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1) and organ failure, and worse clinical outcomes.

Clinical factors associated with adverse outcomes in the acute period of management of submassive pulmonary embolism.

The majority of patients with intermediate-to-severe submassive pulmonary embolism are hemodynamically stable upon presentation. There is a lack of evidence for the clinical relevance and safety of initially employed therapies in this population. The objective of current analysis was to determine predictors associated with adverse outcomes in submassive pulmonary embolism patients. This was a single-center, retrospective chart review identifying patient characteristics and clinical factors associated with adverse outcomes within the management of patients presenting to the emergency department for submassive pulmonary embolism. A total of 122 admissions for submassive pulmonary embolism were included. Among these patients, 41% (n = 50) of admissions had an adverse outcomes. Fluid volume was associated with adverse events in an incremental manner (odds ratio 2.1, 95% confidence interval, 1.4-3.2). These findings demonstrate a significant incidence of adverse events in patients with submassive pulmonary embolism and an incremental increase in likelihood of adverse events with each liter of fluid.

Sex and Racial Differences in High-Density Lipoprotein Levels in Acute Coronary Syndromes.

BACKGROUND: This study aimed to assess sex and racial differences related to high-density lipoprotein cholesterol (HDL-C) levels in those presenting with acute coronary syndromes (ACS). METHODS: Records from patients with ACS presenting to the Emergency Department of University of Florida Hospital Jacksonville from 2009 to 2012, were reviewed. Detailed medical history was obtained. HDL-C levels were measured within 72 h of presentation. Pearson chi-square and Wilcoxon rank sum tests were used to compare groups in univariate analysis. Analysis of variance was performed to determine independent predictors of higher HDL-C levels using variable selection. RESULTS: Of 2400 patients screened, 614 (382 men and 232 women) met inclusion criteria. Hypertension, chronic kidney disease or prior CAD history was similar between sexes and races. Women were more likely to be older (62.4 vs 58.4 years), diabetic (56.5 vs 36.5%) and have higher body mass index (31.2 vs 30.1 kg/m2). Blacks were more likely to be diabetic (50.3 vs 41.3%). After adjusting for all clinical markers, women and blacks along with absence of CAD or diabetes, were significantly associated with higher HDL-C levels. CONCLUSIONS: High HDL-C levels (> 40 mg/dL), considered cardio-protective, were seen in women and blacks with ACS more often than in men and whites. Significant differences in HDL-C levels between sexes were seen in whites but not in blacks. Relevance and quality of HDL-C levels in racial groups need further study as this may have important implications in the interpretation of current guidelines.

Opioid Overdose Risk in Patients Returning to the Emergency Department for Pain.

OBJECTIVE: Using the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) in patients returning to the emergency department (ED) for pain and discharged with an opioid prescription, we assessed overall opioid overdose risk and compared risk in opioid naive patients to those who are non-opioid naive. DESIGN: This was a secondary analysis from a prospective observational study of patients ≥ 18 years old returning to the ED within 30 days. Data were collected from patient interviews and chart reviews. Patients were categorized as Group 1 (not using prescription opioids) or Group 2 (consuming prescription opioids). Statistical analyses were performed using Fisher's exact and Wilcoxon's rank sum tests. Risk class and probability of overdose was determined using Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD). RESULTS: Of the 389 enrollees who returned to the ED due to pain within 30 days of an initial visit, 67 (17%) were prescribed opioids. The majority of these patients were in Group 1 (60%). Both Group 1 (n = 40) and Group 2 (n = 27) held an average CIP-RIOSORD risk class of 3. Race significantly differed between groups; the majority of Group 1 self-identified as African American (80%) (P = .0267). There were no differences in age, gender, or CIP-RIOSORD risk class between groups. However, Group 2 had nearly double the number of predictive factors (median = 1.93) as Group 1 (median = 1.18) (P = .0267). CONCLUSIONS: A substantial proportion of patients (25%) were high risk for opioid overdose. CIP-RIOSORD may prove beneficial in risk stratification of patients discharged with prescription opioids from the ED.

Effect of atorvastatin on lipogenic, inflammatory and thrombogenic markers in women with the metabolic syndrome.

BACKGROUND AND AIM: Specific drug therapy to target the underlying proinflammatory and prothrombotic state in patients with metabolic syndrome (MS) is lacking. We sought to study the effect of high-intensity atorvastatin on markers of lipogenesis, inflammation and thrombogenesis, in women with MS in the absence of cardiovascular disease or diabetes. METHODS AND RESULTS: This randomized double-blinded controlled trial included 88 women with MS (according to National Cholesterol Education Panel Adult Treatment Panel III criteria) and low atherosclerotic cardiovascular risk. Participants were randomized to receive atorvastatin 80 mg or matching placebo. Thrombogenic, lipogenic and inflammatory markers were collected at the time of enrollment, after a 6-week dietary run-in phase (time of randomization), and at 6- and 12-weeks after randomization. At 6 weeks post-randomization, there was significant reduction in total cholesterol, low density lipoprotein cholesterol, triglycerides, apolipoprotein-B (Apo-B) and Apo-B/Apo-A1 ratio in the atorvastatin arm compared to placebo. This difference persisted at 12-weeks post randomization. There was no significant difference in fasting blood glucose, high-density lipoprotein cholesterol, high sensitivity C-reactive protein, serum leptin, Apo-A1, intercellular adhesion molecule 1 and platelet activity. A significant increase in vascular adhesion molecule 1 at 6 and 12 weeks was seen within the atorvastatin arm. No difference was observed in blood pressure and waist circumference. CONCLUSIONS: In conclusion, high-intensity atorvastatin has an early and significant impact on lipoproteins and apolipoproteins but did not lower inflammatory, thrombogenic or biomarkers of platelet activity and aggregation in women with MS. The use of statins for primary prevention in these patients should be further explored.