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Background Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy is showing promising efficacy for treatment of cystic fibrosis (CF) and is becoming more widely available since recent FDA approval. However, little is known about how these drugs will affect lung infections, which are the leading cause of morbidity and mortality among people with CF (pwCF). Methods We analyzed sputum microbiome and metabolome data from pwCF (n=24) before and after ETI therapy using 16S rRNA gene sequencing and untargeted metabolomics. Results The sputum microbiome diversity, particularly its evenness, was increased (p=0.036) and the microbiome profiles were different between individuals before and after therapy (PERMANOVA F=1.92, p=0.044). Despite these changes, the microbiomes remained more similar within an individual than across the sampled population. No specific microbial taxa differed in relative abundance before and after therapy, but the collective log-ratio of classic CF pathogens to anaerobes significantly decreased (p=0.013). The sputum metabolome also showed changes associated with ETI (PERMANOVA F=4.22, p=0.002) and was characterized by greater variation across subjects while on treatment. Changes in the metabolome were driven by a decrease in peptides, amino acids, and metabolites from the kynurenine pathway, which were associated with a decrease in CF pathogens. Metabolism of the three small molecules that make up ETI was extensive, including previously uncharacterized structural modifications. Conclusions ETI therapy is associated with a changing microbiome and metabolome in airway mucus. This effect was stronger on sputum biochemistry, which may reflect changing niche space for microbial residency in lung mucus as the drug's effects take hold. Funding This project was funded by a National Institute of Allergy and Infectious Disease Grant R01AI145925

BACKGROUND: The 12-lead ECG plays an important role in triaging patients with symptomatic coronary artery disease, making automated ECG interpretation statements of “Acute MI” or “Acute Ischemia” crucial, especially during prehospital transport when access to physician interpretation of the ECG is limited. However, it remains unknown how automated interpretation statements correspond to adjudicated clinical outcomes during hospitalization. We sought to evaluate the diagnostic performance of prehospital automated interpretation statements to four well-defined clinical outcomes of interest: confirmed ST- segment elevation myocardial infarction (STEMI); presence of actionable coronary culprit lesions, myocardial necrosis, or any acute coronary syndrome (ACS). METHODS: An observational cohort study that enrolled consecutive patients with non-traumatic chest pain transported via ambulance. Prehospital ECGs were obtained with the Philips MRX monitor from the medical command center and re-processed using manufacturer-specific diagnostic algorithms to denote the likelihood of >>>Acute MI<<< or >>>Acute Ischemia<<

Background: Research networks need access to EMS data to conduct pilot studies and determine feasibility of prospective studies. Combining data across EMS agencies is complicated and costly. Leveraging the National EMS Information System (NEMSIS) to extract select agencies’ data may be an efficient and cost-effective method of providing network-level data. Objective: Describe the process of creating a Pediatric Emergency Care Applied Research Network (PECARN) specific NEMSIS data set and determine if these data were nationally representative. Methods: We established data use agreements (DUAs) with EMS agencies participating in PECARN to allow for agency identification through NEMSIS. Using 2019 NEMSIS version 3.4.0 data for EMS events with patients 18 years old and younger, we compared PECARN NEMSIS data to national NEMSIS data. Analyzed variables were selected for their ability to characterize events. No statistical analyses were utilized due to the large sample, instead, differences of ±5% were deemed clinically meaningful. Results: DUAs were established for 19 EMS agencies, creating a PECARN data set with 305,188 EMS activations of which 17,478 (5.7%) were pediatric. Of the pediatric activations, 17,140 (98.1%) were initiated through 9-1-1 and 9,487 (55.4%) resulted in transport by the documenting agency. The national data included 36,288,405 EMS activations of which 2,152,849 (5.9%) were pediatric. Of the pediatric activations 1,704,141 (79.2%) were initiated through 9-1-1 and 1,055,504 (61.9%) were transported by the documenting agency. Age and gender distributions were similar between the two groups, but the PECARN-specific data under-represents Black and Latinx patients. Comparison of EMS provider primary impressions revealed that three of the five most common were similar with injury being the most prevalent for both data sets along with mental/behavioral health and seizure. Conclusion: We demonstrated that NEMSIS can be leveraged to create network specific data sets. PECARN’s EMS data were similar to the national data, though racial/ethnic minorities and some primary impressions may be under-represented. Additionally, more EMS activations in PECARN study areas originated through 9-1-1 but fewer were transported by the documenting agency. This is likely related to the type of participating agencies, their ALS response level, and the diversity of the communities they serve.

To describe the epidemiology of emergency department (ED) visits by pediatric patients transported from the out-of-hospital setting (ie, scene) by emergency medical services (EMS), and identify factors associated with EMS transport.We performed a cross-sectional study of ED visits from 2014 to 2017 utilizing a nationally representative probability sample survey of visits to US EDs. We included pediatric patients (18 years old) and compared encounters transported from the scene by EMS to those who arrived to the ED by all other means. We performed multivariable logistic regression to identify factors associated with scene EMS transport.Of 130.2 million pediatric ED encounters, 4.7 million (3.8%) arrived by EMS. Most patients were White (61.1%), non-Hispanic (77.5%), and publicly insured (52.2%). Multivariable analysis demonstrated associations with EMS transport: Black (vs White) race (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.16-1.89), ages 1 to younger than 5 years (aOR, 0.52; 95% CI, 0.37-0.72) and 5 to younger than 12 years (aOR, 0.56; 95% CI, 0.40-0.80) (vs adolescents), pediatric (aOR, 0.60; 95% CI, 0.42-0.85) and nonmetropolitan hospital status (aOR, 0.52; 95% CI, 0.35-0.78), blood testing (aOR, 2.34; 95% CI, 1.71-3.19), time to evaluation (31-60 minutes [aOR, 0.56; 95% CI, 0.39-0.80] and60 minutes [aOR, 0.51; 95% CI, 0.33-0.77] compared with 0-30 minutes), admission (aOR, 3.20; 95% CI, 2.33-4.38), and trauma (1.80; 95% CI, 1.43-2.28).Four percent of pediatric ED patients are transported to the ED by EMS from the scene. These patients receive a rapid and resource intense diagnostic evaluation, suggesting that higher acuity. Black patients, adolescents, and those with trauma were more likely to be transported by EMS.

SummaryThe current paradigm is that inflammatory pain passively resolves following the cessation of inflammation. Yet, in a substantial proportion of patients with inflammatory diseases, resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain. Mechanistic insight how inflammatory pain is resolved is lacking. Here we show that macrophages actively control resolution of inflammatory pain remotely from the site of inflammation by transferring mitochondria to sensory neurons. During resolution of inflammatory pain in mice, M2-like macrophages infiltrate the dorsal root ganglia that contain the somata of sensory neurons, concurrent with the recovery of oxidative phosphorylation in sensory neurons. The resolution of pain and the transfer of mitochondria requires expression of CD200 Receptor (CD200R) on macrophages and the non-canonical CD200R-ligand iSec1 on sensory neurons. Our data reveal a novel mechanism for active resolution of inflammatory pain.Graphical Abstract

Prompt identification of acute coronary syndrome is a challenge in clinical practice. The 12-lead electrocardiogram (ECG) is readily available during initial patient evaluation, but current rule-based interpretation approaches lack sufficient accuracy. Here we report machine learning-based methods for the prediction of underlying acute myocardial ischemia in patients with chest pain. Using 554 temporal-spatial features of the 12-lead ECG, we train and test multiple classifiers on two independent prospective patient cohorts (n = 1244). While maintaining higher negative predictive value, our final fusion model achieves 52% gain in sensitivity compared to commercial interpretation software and 37% gain in sensitivity compared to experienced clinicians. Such an ultra-early, ECG-based clinical decision support tool, when combined with the judgment of trained emergency personnel, would help to improve clinical outcomes and reduce unnecessary costs in patients with chest pain., Diagnosing a heart attack requires excessive testing and prolonged observation, which frequently requires hospital admission. Here the authors report a machine learning-based system based exclusively on ECG data that can help clinicians identify 37% more heart attacks during initial screening.

Background The Emergency Severity Index (ESI) is a widely used tool to triage patients in emergency departments. The ESI tool is used to assess all complaints and has significant limitation for accurately triaging patients with suspected acute coronary syndrome (ACS). Objective We evaluated the accuracy of ESI in predicting serious outcomes in suspected ACS and aimed to assess the incremental reclassification performance if ESI is supplemented with a clinically validated tool used to risk-stratify suspected ACS. Methods We used existing data from an observational cohort study of patients with chest pain. We extracted ESI scores documented by triage nurses during routine medical care. Two independent reviewers adjudicated the primary outcome, incidence of 30-day major adverse cardiac events. We compared ESI with the well-established modified HEAR/T (patient History, Electrocardiogram, Age, Risk factors, but without Troponin) score. Results Our sample included 750 patients (age, 59 ± 17 years; 43% female; 40% black). A total of 145 patients (19%) experienced major adverse cardiac event. The area under the receiver operating characteristic curve for ESI score for predicting major adverse cardiac event was 0.656, compared with 0.796 for the modified HEAR/T score. Using the modified HEAR/T score, 181 of the 391 false positives (46%) and 16 of the 19 false negatives (84%) assigned by ESI could be reclassified correctly. Conclusion The ESI score is poorly associated with serious outcomes in patients with suspected ACS. Supplementing the ESI tool with input from other validated clinical tools can greatly improve the accuracy of triage in patients with suspected ACS.

Objective The objective of this study was to compare statewide prehospital protocols for the management of pediatric seizures. Methods We performed a descriptive analysis comparing statewide protocols for emergency medical services management of pediatric seizures within the United States, excluding states for which no statewide protocol/model was available. We compared antiepileptic drugs (AEDs), routes and doses of administration, and differences in febrile seizure management. Results Of 50 states, 34 had either statewide protocols or models and were included. All had a protocol for the management of seizures and provided specific recommendations for the management of pediatric seizures. Twelve states (35%) preferentially recommended midazolam over other benzodiazepines. Thirty-two (94%) of 34 allowed for use of midazolam, with variable use of other AEDs. All allowed for use of intramuscular AED. Twenty-six (77%) allowed for intranasal AED. Nine (27%) allowed emergency medical services to administer a patient's own abortive AED, and 6 (18%) allowed for use of a patient's vagal nerve stimulator, when present. There was a wide variability with respect to dosing ranges for medications. Thirty-two (94%) of 34 included blood glucose measurement within the protocol. Twenty-one protocols (62%) provided recommendations for febrile seizures, including recommending active/passive cooling (8/34, 24%) and antipyretic administration (9/34, 26%). Conclusions All statewide protocols carried specific guidelines for the prehospital management of pediatric seizures; however, there was wide variability with respect to specific AEDs, routes of administration, and drug dosages. In addition to broader availability of statewide guidance, areas of potential protocol improvement and research include AED dose optimization, reprioritization of blood glucose, and greater emphasis on intranasal or intramuscular medication dosing.

Background: Prehospital pediatric endotracheal intubation (ETI) is rarely performed. Previous research has suggested that pediatric prehospital ETI, when performed by ground advanced life support c...

Background Delay in seeking medical treatment for suspected acute coronary syndrome can lead to negative patient outcomes. Objective Our aim was to evaluate the prevalence and predictors of delay in seeking care in high-risk chest pain patients with or without acute coronary syndrome (ACS). Methods This was a secondary analysis of an observational cohort study of patients transported by Emergency Medical Services for a chief complaint of chest pain. Important demographic and clinical characteristics were extracted from electronic health records. Two independent reviewers adjudicated the presence of ACS. Logistic regression was used to model the predictors of delay in seeking care. Results The final sample included 743 patients (99% non-Hispanic). Overall, 24% presented > 12 h from onset of symptoms. Among those with ACS (n = 115), 14% presented > 12 h after onset of symptoms. Race, smoking, diabetes, and related symptoms were associated with delayed seeking behavior. In multivariate analysis, non-Caucasian race (black or others) was the only independent predictor of > 12 h delay in seeking care (odds ratio 1.4; 95% confidence interval 1.0–1.9). Conclusions One in four patients with chest pain, including 14% of those with ACS, wait more than 12 h before seeking care. Compared to non-blacks, black patients are 40% more likely to delay seeking care > 12 h.

BACKGROUND Asthma is a common pediatric diagnosis for emergency medical services (EMS) transports, however there is a paucity of data on prehospital asthma management. The purpose of this study was to describe prehospital management of pediatric patients with suspected asthma exacerbation. METHODS We conducted a retrospective review of electronic medical records from 24 ground EMS agencies in Southwestern Pennsylvania between 1 January 2014 to 31 December 2017. We identified patients 2 to 17 years with documented wheezing, excluding those with suspected anaphylaxis. Patients with documented respiratory distress were classified as severe asthma. We report descriptive statistics of demographics, vital signs, and management including administration of medications and performance of procedures. RESULTS Of 19 246 pediatric transports, 1078 (5.6%) patients had wheezing. Of these, 532 (49%) met criteria for severe asthma. Patients with severe asthma were more likely to be adolescents compared to those with nonsevere asthma (49.6% vs 6%; P < .001). While rates of intravenous methylprednisolone administration were higher in patients with severe asthma (68/532, 12.8%) compared to those with nonsevere asthma (13/546, 2.4%; P < .001), overall use of steroids was low (7.5%). Other therapies provided included albuterol (n = 699, 64.8%), ipratropium bromide (n = 271, 25.1%), and oxygen (n = 280, 26.0%). One hundred eighty patients (16.7%) received a peripheral IV line. Two patients (0.4%) were given continuous positive airway pressure. CONCLUSION Approximately 6% of pediatric EMS transports are for asthma. Steroid usage was low in even those with severe asthma, representing an area of process improvement. These data provide a baseline to future research to identify interventions that may improve outcomes.

Healthcare disparities in the initial management of patients with acute coronary syndrome (ACS) exist. Yet, the complexity of interactions between demographic, social, economic, and geospatial determinants of health hinders incorporating such predictors in existing risk stratification models. We sought to explore a machine-learning-based approach to study the complex interactions between the geospatial and social determinants of health to explain disparities in ACS likelihood in an urban community. This study identified consecutive patients transported by Pittsburgh emergency medical service for a chief complaint of chest pain or ACS-equivalent symptoms. We extracted demographics, clinical data, and location coordinates from electronic health records. Median income was based on US census data by zip code. A random forest (RF) classifier and a regularized logistic regression model were used to identify the most important predictors of ACS likelihood. Our final sample included 2400 patients (age 59 ± 17 years, 47% Females, 41% Blacks, 15.8% adjudicated ACS). In our RF model (area under the receiver operating characteristic curve of 0.71 ± 0.03) age, prior revascularization, income, distance from hospital, and residential neighborhood were the most important predictors of ACS likelihood. In regularized regression (akaike information criterion = 1843, bayesian information criterion = 1912, χ2 = 193, df = 10, p

Background Novel temporal-spatial features of the 12‑lead ECG can conceptually optimize culprit lesions' detection beyond that of classical ST amplitude measurements. We sought to develop a data-driven approach for ECG feature selection to build a clinically relevant algorithm for real-time detection of culprit lesion. Methods This was a prospective observational cohort study of chest pain patients transported by emergency medical services to three tertiary care hospitals in the US. We obtained raw 10-s, 12‑lead ECGs (500 s/s, HeartStart MRx, Philips Healthcare) during prehospital transport and followed patients 30 days after the encounter to adjudicate clinical outcomes. A total of 557 global and lead-specific features of P-QRS-T waveform were harvested from the representative average beats. We used Recursive Feature Elimination and LASSO to identify 35/557, 29/557, and 51/557 most recurrent and important features for LAD, LCX, and RCA culprits, respectively. Using the union of these features, we built a random forest classifier with 10-fold cross-validation to predict the presence or absence of culprit lesions. We compared this model to the performance of a rule-based commercial proprietary software (Philips DXL ECG Algorithm). Results Our sample included 2400 patients (age 59 ± 16, 47% female, 41% Black, 10.7% culprit lesions). The area under the ROC curves of our random forest classifier was 0.85 ± 0.03 with sensitivity, specificity, and negative predictive value of 71.1%, 84.7%, and 96.1%. This outperformed the accuracy of the automated interpretation software of 37.2%, 95.6%, and 92.7%, respectively, and corresponded to a net reclassification improvement index of 23.6%. Metrics of ST80; Tpeak-Tend; spatial angle between QRS and T vectors; PCA ratio of STT waveform; T axis; and QRS waveform characteristics played a significant role in this incremental gain in performance. Conclusions Novel computational features of the 12‑lead ECG can be used to build clinically relevant machine learning-based classifiers to detect culprit lesions, which has important clinical implications.

Background: Immunity against Pasteurella spp. is not well-known for humans.Methods: We've tested T CD8+ lymphocytes in a patient with a chronic prosthetic joint infection due to Pasteurella spp. to search for a deficit which could have favored her infection. As this deficit was found, we've searched for such a deficit in other patients with Pasteurella spp. Infections, either acute or subacute.Results: Eight patients were tested and all had a persistent T CD8+ lymphocytes deficit. This is striking as these cells are involved in the response to this type of infection in animal models.Conclusion: The authors suggest that a deficit in CD8+ T lymphocytes can be one of the causes for the onset of infections with P. multocida.

Background: Naloxone is widely available to bystanders and first responders to treat patients with suspected opioid overdose. In these patients, the prognostic factors and potential benefits associ...

BackgroundInhospital stroke (IHS) is associated with high morbidity and mortality, likely related to multiple factors, including delayed time to recognition, associated comorbidities, and initial care from non-stroke trained providers. We hypothesized that guided revision of a formalized ‘stroke code’ system can improve diagnosis and time to thrombolysis and thrombectomy.MethodsIHS activations occurring at a comprehensive stroke center between 2013 and 2016 were retrospectively analyzed to guide revisions of an established stroke code protocol to improve provider communication and time to imaging, reduce stroke mimic rate, and improve the use of parallel processing. After protocol implementation, we prospectively collected data between 2016 and 2017 for comparison with the pre-implementation group, including diagnostic accuracy and relevant time points (code call to examination, examination to imaging, and imaging to intervention). We report descriptive statistics for comparison of patient characteristics and time metrics (time to imaging and reperfusion after IHS activation). Multivariable regression analysis was performed to identify independent predictors of stroke mimics and time metrics.ResultsThere were 136 cases in the pre-implementation group and 69 in the post-implementation group. A reduction in stroke mimics (52% vs 33%, P=0.01) occurred after protocol initiation. Mean time to imaging after stroke code call was 7.6 min shorter (P=0.026) and mean time from imaging to acute reperfusion therapy was 45.7 vs 19.8 min (P=0.05) in the pre- versus the post-implementation group.ConclusionRevision of an existing IHS protocol was associated with a lower rate of stroke mimics, and a shorter time to intravenous and intra-arterial intervention.

BACKGROUND: Nonspecific ST-T repolarization (NST) abnormalities alter the ST-segment for reasons often unrelated to acute myocardial ischemia, which could contribute to misdiagnosis or inappropriate treatment. We sought to define the prevalence of NST patterns in patients with chest pain and evaluate how such patterns correlate with the eventual etiology of chest pain and course of hospitalization. METHODS: This was a prospective observational study that included consecutive prehospital chest pain patients from three tertiary care hospitals in the U.S. Two independent reviewers blinded from clinical data audited the prehospital 12-lead ECG for the presence or absence of NST patterns (i.e., right or left bundle branch block, left ventricular hypertrophy with strain pattern, ventricular pacing, ventricular rhythm, or coarse atrial fibrillation). The primary outcome was 30-day major adverse cardiac events (MACE) defined as cardiac arrest, acute heart failure, post-discharge infarction, or all-cause death. RESULTS: The final sample included 750 patients (age 59±17, 58% males). A total of 40 patients (5.3%) experienced 30-MACE and 131 (17.5%) had NST patterns. The presence of NST patterns was an independent multivariate predictor of 30-day MACE (9.9% vs. 4.4%, OR = 2.2 [95% CI = 1.1–4.5]. Patients with NST patterns had increased median length of stay (1.0 [IQR 0.5–3] vs. 2.0 [IQR 1–4] days, p

Introduction Appropriate prehospital (PH) triage of patients with chest pain can significantly improve outcomes in acute myocardial infarction (MI). We sought to explore how PH providers triage chest pain as high versus low risk and to evaluate the accuracy and predictors of their triage decision. Methods This was a prospective, observational cohort study that enrolled consecutive patients with chest pain transported by emergency medical services (EMS) to 3 tertiary care hospitals in the US. EMS triage decision (high risk versus low-risk) was defined based on the transmission of PH electrocardiogram (ECG) to a command center for medical consultation with or without catheter laboratory activation. Two independent reviewers examined in-hospital medical records to adjudicate the presence of acute MI and to audit the findings on the presenting ECG. Results We enrolled 2,065 patients (aged 56 ± 17, 53% male) of whom 768 (37%) were triaged as high risk. Those triaged as high risk were older, were more likely to be men or have significant cardiac history, and had a higher rate of acute MI events (14.2% versus 3.5%). The sensitivity and specificity for triaging MI events as high risk were 70% and 97%, respectively. A total of 46/155 (30%) MI events were misclassified as low risk. No previous coronary revascularization and ECG misinterpretation were strong independent predictors of such undertriage. Conclusions PH providers have moderate sensitivity in triaging high-risk patients; 1 in 3 MI events are undertriaged. Emergency nurses need to pay special attention to patients with benign past histories during transition of care and should always reinterpret ECGs for subtle ischemic changes.

Background The acute respiratory distress syndrome (ARDS) is a serious disease in critically ill patients that is characterized by pulmonary dysfunctions, hypoxemia and significant mortality. Patients with immunodeficiency (e.g. SCID with T and B cell deficiency) are particularly susceptible to the development of severe ARDS. However, the role of T cells on pulmonary dysfunctions in immune-competent patients with ARDS is only incompletely understood. Methods Wild-type (wt) and RAG2−/− mice (lymphocyte deficient) received intratracheal instillations of LPS (4 mg/kg) or saline. On day 1, 4 and 10 lung mechanics and bronchial hyperresponsiveness towards acetylcholine were measured with the flexiVent ventilation set-up. The bronchoalveolar lavage fluid (BALF) was examined for leukocytes (FACS analysis) and pro-inflammatory cytokines (ELISA). Results In wt mice, lung mechanics, body weight and body temperature deteriorated in the LPS-group during the early phase (up to d4); these alterations were accompanied by increased leukocyte numbers and inflammatory cytokine levels in the BALF. During the late phase (day 10), both lung mechanics and the cell/cytokine homeostasis recovered in LPS-treated wt mice. RAG2−/− mice experienced changes in body weight, lung mechanics, BAL neutrophil numbers, BAL inflammatory cytokines levels that were comparable to wt mice. Conclusion Following LPS instillation, lung mechanics deteriorate within the first 4 days and recover towards day 10. This response is not altered by the lack of T lymphocytes suggesting that T cells play only a minor role for the initiation, propagation or recovery of LPS-induced lung dysfunctions or function of T lymphocytes can be compensated by other immune cells, such as alveolar macrophages. Electronic supplementary material The online version of this article (10.1186/s12890-018-0741-2) contains supplementary material, which is available to authorized users.

Background There is an emerging body of evidence that links exposure to shift work to cardiovascular disease (CVD). The risk of coronary events, such as myocardial infarction, is greater among night shift workers compared to day workers. There is reason to believe that repeated exposure to shift work, especially night shift work, creates alterations in normal circadian patterns of blood pressure (BP) and heart rate variability (HRV) and that these alterations contribute to increased risk of CVD. Recent data suggest that allowing shift workers to nap during night shifts may help to normalize BP and HRV patterns and, over time, reduce the risk of CVD. The risk of CVD related to shift work is elevated for emergency medical services (EMS) shift workers due in part to long-duration shifts, frequent use of night shifts, and a high prevalence of multiple jobs. Methods We will use a randomized crossover trial study design with three study conditions. The targeted population is comprised of EMS clinician shift workers, and our goal enrollment is 35 total participants with an estimated 10 of the 35 enrolled not completing the study protocol or classified as lost to attrition. All three conditions will involve continuous monitoring over 72 h and will begin with a 36-h at-home period, followed by 24 total hours in the lab (including a 12-h simulated night shift), ending with 12 h at home. The key difference between the three conditions is the intra-shift nap. Condition 1 will involve a simulated 12-h night shift with total sleep deprivation. Condition 2 will involve a simulated 12-h night shift and a 30-min nap opportunity. Condition 3 will involve a simulated 12-h night shift with a 2-h nap opportunity. Our primary outcomes of interest include blunted BP dipping and reduced HRV as measured by the standard deviation of the inter-beat intervals of normal sinus beats. Non-dipping status will be defined as sleep hours BP dip of less than 10%. Discussion Our study will address two indicators of cardiovascular health and determine if shorter or longer duration naps during night shifts have a clinically meaningful impact. Trial registration ClinicalTrials.gov NCT04469803. Registered on 9 July 2020

Background Classical ST‐T waveform changes on standard 12‐lead ECG have limited sensitivity in detecting acute coronary syndrome (ACS) in the emergency department. Numerous novel ECG features have been previously proposed to augment clinicians' decision during patient evaluation, yet their clinical utility remains unclear. Methods and Results This was an observational study of consecutive patients evaluated for suspected ACS (Cohort 1 n=745, age 59±17, 42% female, 15% ACS; Cohort 2 n=499, age 59±16, 49% female, 18% ACS). Out of 554 temporal‐spatial ECG waveform features, we used domain knowledge to select a subset of 65 physiology‐driven features that are mechanistically linked to myocardial ischemia and compared their performance to a subset of 229 data‐driven features selected by multiple machine learning algorithms. We then used random forest to select a final subset of 73 most important ECG features that had both data‐ and physiology‐driven basis to ACS prediction and compared their performance to clinical experts. On testing set, a regularized logistic regression classifier based on the 73 hybrid features yielded a stable model that outperformed clinical experts in predicting ACS, with 10% to 29% of cases reclassified correctly. Metrics of nondipolar electrical dispersion (ie, circumferential ischemia), ventricular activation time (ie, transmural conduction delays), QRS and T axes and angles (ie, global remodeling), and principal component analysis ratio of ECG waveforms (ie, regional heterogeneity) played an important role in the improved reclassification performance. Conclusions We identified a subset of novel ECG features predictive of ACS with a fully interpretable model highly adaptable to clinical decision support applications. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT04237688.

Cells : open access journal 10(5), 1210 (2021). doi:10.3390/cells10051210 special issue: "Topical collection "The endothelial cell in lung inflammation" / editor: Konstantin G. Birukov, collection editor", Published by MDPI, Basel

Pain is the major debilitating symptom of osteoarthritis (OA), which is difficult to treat. In OA patients joint tissue damage only poorly associates with pain, indicating other mechanisms contribute to OA pain. Immune cells regulate the sensory system, but little is known about the involvement of immune cells in OA pain. Here, we report that macrophages accumulate in the dorsal root ganglia (DRG) distant from the site of injury in two rodent models of OA. DRG macrophages acquired an M1-like phenotype, and depletion of DRG macrophages resolved OA pain in male and female mice. Sensory neurons innervating the damaged knee joint shape DRG macrophages into an M1-like phenotype. Persisting OA pain, accumulation of DRG macrophages, and programming of DRG macrophages into an M1-like phenotype were independent of Nav1.8 nociceptors. Inhibition of M1-like macrophages in the DRG by intrathecal injection of an IL4-IL10 fusion protein or M2-like macrophages resolved persistent OA pain. In conclusion, these findings reveal a crucial role for macrophages in maintaining OA pain independent of the joint damage and suggest a new direction to treat OA pain.SIGNIFICANCE STATEMENT In OA patients pain poorly correlates with joint tissue changes indicating mechanisms other than only tissue damage that cause pain in OA. We identified that DRG containing the somata of sensory neurons innervating the damaged knee are infiltrated with macrophages that are shaped into an M1-like phenotype by sensory neurons. We show that these DRG macrophages actively maintain OA pain remotely and independent of joint damage. The phenotype of these macrophages is crucial for a pain-promoting role. Targeting the phenotype of DRG macrophages with either M2-like macrophages or a cytokine fusion protein that skews macrophages into an M2-like phenotype resolves OA pain. Our work reveals a mechanism that contributes to the maintenance of OA pain distant from the affected knee joint and suggests that dorsal root ganglia macrophages are a target to treat osteoarthritis chronic pain.

Emergency department (ED) nurses need to identify patients with potential acute coronary syndrome (ACS) rapidly because treatment delay could impact patient outcomes. Aims of this secondary analysis were to identify key patient factors that could be available at initial ED nurse triage that predict ACS. Consecutive patients with chest pain who called 9-1-1, received a 12-lead electrocardiogram in the prehospital setting, and were transported via emergency medical service were included in the study. A total of 750 patients were recruited. The sample had an average age of 59 years old, was 57% male, and 40% Black. One hundred and fifteen patients were diagnosed with ACS. Older age, non-Caucasian race, and faster respiratory rate were independent predictors of ACS. There was an interaction between heart rate by Type II diabetes receiving insulin in the context of ACS. Type II diabetics requiring insulin for better glycemic control manifested a faster heart rate. By identifying patient factors at ED nurse triage that could be predictive of ACS, accuracy rates of triage may improve, thus impacting patient outcomes.

Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1–3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of—and interplay between—novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans. © 2020, The Author(s), under exclusive licence to Springer Nature Limited., Wellcome Trust, WT: 104807/Z/14/Z University College London, UCL: 100140/Z/12/Z, 107212/Z/15/Z, MR/L019027, 203141/Z/16/Z, 091157/Z/10/Z Bundesministerium für Bildung und Forschung, BMBF: 01ZX1306A University of Cambridge 201250/Z/16/Z 01ZX1709 Seventh Framework Programme, FP7 NIHR Bristol Biomedical Research Centre Deutsche Forschungsgemeinschaft, DFG Deutsche Forschungsgemeinschaft, DFG: EXC 2167-390884018 Juvenile Diabetes Research Foundation United Kingdom, JDRF: 9-2011-253, 5-SRA-2015-130-A-N National Institute for Health Research, NIHR: RG65966 Medical Research Council, MRC: RG95376, MR/L006197/1 Great Ormond Street Hospital for Children, GOSH, Acknowledgements The NBR-RD PID Consortium is part of the NIHR BioResource, for which funding was provided by the NIHR (NIHR, grant number RG65966). We acknowledge the participation of all NIHR BioResource volunteers, and thank the NIHR BioResource centre and staff for their contribution. J.E.D.T. is supported by the Medical Research Council (MRC) (RG95376 and MR/L006197/1); A.J.T. is supported by the Wellcome Trust (104807/Z/14/Z) and the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London; K.G.C.S. is supported by the MRC (programme grant MR/L019027) and is a Wellcome Investigator; A.J.C. was supported by the Wellcome Trust (091157/Z/10/Z, 107212/Z/15/Z, 100140/Z/12/Z, 203141/Z/16/Z), JDRF (9-2011-253, 5-SRA-2015-130-A-N), NIHR Oxford Biomedical Research Centre and NIHR Cambridge Biomedical Research Centre; E.E. has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement number 609020-Scientia Fellows; E.R. is supported by the Wellcome Trust (201250/Z/16/Z); D.E. is supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (SysInflame grant 01ZX1306A; GB-XMAP grant 01ZX1709) and funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) under Germany’s Excellence Strategy (EXC 2167-390884018). The NIHR Cambridge Biomedical Research Centre (BRC) is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the NIHR. This research was co-funded by the support listed above and the NIHR Cambridge BRC.

Introduction Levosimendan is approved for acute heart failure. Within this context, pulmonary hypertension represents a frequent co-morbidity. Hence, the effects of levosimendan on segmental pulmonary vascular resistance (PVR) are relevant. So far, this issue has been not studied. Beyond that the relaxant effects of levosimendan in human pulmonary vessel are unknown. We addressed these topics in rats’ isolated perfused lungs (IPL) and human precision-cut lung slices (PCLS). Material and methods In IPL, levosimendan (10 μM) was perfused in untreated and endothelin-1 pre-contracted lungs. The pulmonary arterial pressure (PPA) was continuously recorded and the capillary pressure (Pcap) was determined by the double-occlusion method. Thereafter, segmental PVR, expressed as precapillary (Rpre) and postcapillary resistance (Rpost) and PVR were calculated. Human PCLS were prepared from patients undergoing lobectomy. Levosimendan-induced relaxation was studied in naive and endothelin-1 pre-contracted PAs and PVs. In endothelin-1 pre-contracted PAs, the role of K+-channels was studied by inhibition of KATP-channels (glibenclamide), BKCa2+-channels (iberiotoxin) and Kv-channels (4-aminopyridine). All changes of the vascular tone were measured by videomicroscopy. In addition, the increase of cAMP/GMP due to levosimendan was measured by ELISA. Results Levosimendan did not relax untreated lungs or naive PAs and PVs. In IPL, levosimendan attenuated the endothelin-1 induced increase of PPA, PVR, Rpre and Rpost. In human PCLS, levosimendan relaxed pre-contracted PAs or PVs to 137% or 127%, respectively. In pre-contracted PAs, the relaxant effect of levosimendan was reduced, if KATP- and Kv-channels were inhibited. Further, levosimendan increased cGMP in PAs/PVs, but cAMP only in PVs. Discussion Levosimendan reduces rats’ segmental PVR and relaxes human PAs or PVs, if the pulmonary vascular tone is enhanced by endothelin-1. Regarding levosimendan-induced relaxation, the activation of KATP- and Kv-channels is of impact, as well as the formation of cAMP and cGMP. In conclusion, our results suggest that levosimendan improves pulmonary haemodynamics, if PVR is increased as it is the case in pulmonary hypertension.

Background Allergic diseases and especially allergic asthma are widespread diseases with high prevalence in childhood, but also in adults. Acid sphingomyelinase (ASM) is a key regulator of the sphingolipid pathway. Previous studies defined the association of ASM with the pathogenesis of TH 1-directed lung diseases like cystic fibrosis and acute lung injury. Here, we define the role of ASM in TH 2-regulated allergic bronchial asthma. Methods To determine the role of Asm under baseline conditions, wild-type (WT) and Asm-/- mice were ventilated with a flexiVent setup and bronchial hyperresponsiveness was determined using acetylcholine. Flow cytometry and cytokine measurements in bronchoalveolar lavage fluid and lung tissue were followed by in vitro TH 2 differentiations with cells from WT and Asm-/- mice and blockade of Asm with amitriptyline. As proof of principle, we conducted an ovalbumin-induced model of asthma in WT- and Asm-/- mice. Results At baseline, Asm-/- mice showed better lung mechanics, but unaltered bronchial hyperresponsiveness. Higher numbers of Asm-/- T cells in bronchoalveolar lavage fluid released lower levels of IL-4 and IL-5, and these results were paralleled by decreased production of typical TH 2 cytokines in Asm-/- T lymphocytes in vitro. This phenotype could be imitated by incubation of T cells with amitriptyline. In the ovalbumin asthma model, Asm-/- animals were protected from high disease activity and showed better lung functions and lower levels of eosinophils and TH 2 cytokines. Conclusion Asm deficiency could induce higher numbers of TH 2 cells in the lung, but those cells release decreased TH 2 cytokine levels. Hereby, Asm-/- animals are protected from bronchial asthma, which possibly offers novel therapeutic strategies, for example, with ASM blockade.

Tumor necrosis factor (TNF) is a well-known mediator of sepsis. In many cases, sepsis results in multiple organ injury including the lung with acute respiratory distress syndrome (ARDS). More than 20-year-old studies have suggested that TNF may be directly responsible for organ injury during sepsis. However, these old studies are inconclusive, because they relied on human rather than conspecific TNF, which was contaminated with endotoxin in most studies. In this study, we characterized the direct effects of intravenous murine endotoxin-free TNF on cardiovascular functions and organ injury in mice with a particular focus on the lungs. Because of the relevance of the acid sphingomyelinase in sepsis, ARDS, and caspase-independent cell death, we also included acid sphingomyelinase-deficient (ASM-/-) mice. ASM-/- and wild-type (WT) mice received 50 μg endotoxin-free murine TNF intravenously alone or in combination with the pan-caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (zVAD) and were ventilated at low tidal volume while lung mechanics were followed. Blood pressure was stabilized by intra-arterial fluid support, and body temperature was kept at 37°C to delay lethal shock and to allow investigation of blood gases, lung histopathology, proinflammatory mediators, and microvascular permeability 6 hours after TNF application. Besides the lungs, also the kidneys and liver were examined. TNF elicited the release of inflammatory mediators and a high mortality rate, but failed to injure the lungs, kidneys, or liver of healthy mice significantly within 6 hours. Mortality in WT mice was most likely due to sepsis-like shock, as indicated by metabolic acidosis, high procalcitonin levels, and cardiovascular failure. ASM-/- mice were protected from TNF-induced hypotension and reflex tachycardia and also from mortality. In WT mice, intravenous exogenous TNF does not cause organ injury but induces a systemic inflammatory response with cardiovascular failure, in which the ASM plays a role.

Objectives. To improve public health surveillance and response by using spatial optimization. Methods. We identified cases of suspected nonfatal opioid overdose events in which naloxone was administered from April 2013 through December 2016 treated by the city of Pittsburgh, Pennsylvania, Bureau of Emergency Medical Services. We used spatial modeling to identify areas hardest hit to spatially optimize naloxone distribution among pharmacies in Pittsburgh. Results. We identified 3182 opioid overdose events with our classification approach, which generated spatial patterns of opioid overdoses within Pittsburgh. We then used overdose location to spatially optimize accessibility to naloxone via pharmacies in the city. Only 24 pharmacies offered naloxone at the time, and only 3 matched with our optimized solution. Conclusions. Our methodology rapidly identified communities hardest hit by the opioid epidemic with standard public health data. Naloxone accessibility can be optimized with established location–allocation approaches. Public Health Implications. Our methodology can be easily implemented by public health departments for automated surveillance of the opioid epidemic and has the flexibility to optimize a variety of intervention strategies.

Background Because local delivery of drugs induces high concentrations, it could be helpful to apply these delivery systems to the treatment of septic arthritis by antibiotics. Thus, a gentamicin-loaded polymer was tested in a rabbit model of Staphylococcus aureus septic arthritis. Methods Thirty New Zealand rabbits were split into five groups: A: infection only; B: infection and systemic gentamicin treatment; C: infection and unloaded polymer and systemic gentamicin treatment; D: infection and gentamicin-loaded polymer only; and E: no infection and unloaded polymer. After inducing nonlethal septic arthritis in the knee joint by injecting 10 colony-forming units (CFUs) of a strain of methicillin-sensitive S aureus in groups A, B, C, and D, rabbits were housed for 15 days, and then the joint capsules were removed and the remaining bacteria were counted. Bacterial load was expressed in CFUs per gram of synovial tissue. In group E, capsules were removed, and a pathologic examination was done. Results At day 15, the bacterial load was 6 × 10, 2 × 10, 1.8 × 10, and 7 × 10 CFU/g of tissue for groups A, B, C, and D, respectively. Compared with the mean of groups A, B, and C, the bacterial load of group D was 4.94 units of log10 CFU/g lower than that of these groups. The bacterial load of group D was statistically significantly lower than that of the other three groups. Noticeably, two animals of group D had a nil bacterial count. In group E animals, a minimal foreign body reaction was observed around the polymer. Discussion Gentamicin-containing microparticles were more efficient in reducing bacterial load than systemic injections of gentamicin and thus have an interesting role to play in the treatment of human arthritis. However, inserting microparticles in joints is not easy, and hydrogels might be a good alternative approach.

As prehospital research advances, more evidence-based guidelines (EBGs) are implemented into emergency medical services (EMS) practice. However, incomplete or suboptimal prehospital EBG implementation may hinder improvement in patient outcomes. To inform future efforts, this study's objective was to review existing evidence pertaining to prehospital EBG implementation methods.This study was a systematic literature review and evaluation following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. PubMed, EMBASE, Scopus, and Google Advanced Search were searched without language or publication date filters for articles addressing prehospital EBG implementation. Conference proceedings, textbooks, and non-English articles were excluded. GRADE was applied to the remaining articles independently by three of five study investigators. Study characteristics and salient findings from the included articles are reported.The systematic literature review identified 1,367 articles, with 41 meeting inclusion criteria. Most articles described prehospital EBG implementation (n = 24, 59%), or implementation barriers (n = 13, 32%). Common study designs were statement documents (n = 12, 29%), retrospective cohort studies (n = 12, 29%), and cross-sectional studies (n = 9, 22%). Using GRADE, evidence quality was rated low (n = 18, 44%), or very low (n = 23, 56%). Salient findings from the articles included: (i) EBG adherence and patient outcomes depend upon successful implementation, (ii) published studies generally lack detailed implementation methods, (iii) EBG implementation takes longer than planned (mostly for EMS education), (iv) EMS systems' heterogeneity affects EBG implementation, and (v) multiple barriers limit successful implementation (e.g., financial constraints, equipment purchasing, coordination with hospitals, and regulatory agencies). This review found no direct evidence for best prehospital EBG implementation practices. There were no studies comparing implementation methods or implementation in different prehospital settings (e.g., urban vs. rural, advanced vs. basic life support).While prehospital EBG implementation barriers are well described, there is a paucity of evidence for optimal implementation methods. For scientific advances to reach prehospital patients, EBG development efforts must translate into EMS practice. Future research should consider comparing implementation methodologies in different prehospital settings, with a goal of defining detailed, reproducible best practices.

Emergency Medical Services (EMS) workers may experience fatigue as a consequence of shift work. We reviewed the literature to determine the impact of caffeine as a countermeasure to fatigue in EMS personnel and related shift workers.We employed the GRADE methodology to perform a systematic literature review and search multiple databases for research that examined the impact of caffeine on outcomes of interest, such as patient and EMS personnel safety. For selected outcomes, we performed a meta-analysis of pooled data and reported the pooled effect in the form of a Standardized Mean Difference (SMD) with corresponding 95% confidence intervals.There are no studies that investigate caffeine use and its effects on EMS workers or on patient safety. Four of 8 studies in shift workers showed that caffeine improved psychomotor vigilance, which is important for performance. Caffeine decreased the number of lapses on a standardized test of performance [SMD = 0.75 (95% CI: 0.30 to 1.19), p = 0.001], and lessened the slowing of reaction time at the end of shifts [SMD = 0.52 (95% CI: 0.19 to 0.85); p = 0.002]. Finally, 2 studies reported that caffeine reduced sleep quality and sleep duration.Although the quality of evidence was judged to be low to moderate, when taken together, these studies demonstrate that caffeine can improve psychomotor performance and vigilance. However, caffeine negatively affects sleep quality and sleep duration. More systematic, randomized studies need to be conducted in EMS workers in order to address the critical outcomes of health and safety of EMS personnel and patients. The risk/benefit ratio of chronic caffeine use in shift workers is currently unknown.

This study comprehensively reviewed the literature on the impact of shorter versus longer shifts on critical and important outcomes for Emergency Medical Services (EMS) personnel and related shift worker groups.Six databases (e.g., PubMed/MEDLINE) were searched, including one website. This search was guided by a research question developed by an expert panel a priori and registered with the PROSPERO database of systematic reviews (2016:CRD42016040099). The critical outcomes of interest were patient safety and personnel safety. The important outcomes of interest were personnel performance, acute fatigue, sleep and sleep quality, retention/turnover, long-term health, burnout/stress, and cost to system. Screeners worked independently and full-text articles were assessed for relevance. Data abstracted from the retained literature were categorized as favorable, unfavorable, mixed/inconclusive, or no impact toward the shorter shift duration. This research characterized the evidence as very low, low, moderate, or high quality according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.The searched yielded n = 21,674 records. Of the 480 full-text articles reviewed, 100 reported comparisons of outcomes of interest by shift duration. We identified 24 different shift duration comparisons, most commonly 8 hours versus 12 hours. No one study reported findings for all 9 outcomes. Two studies reported findings linked to both critical outcomes of patient and personnel safety, 34 reported findings for one of two critical outcomes, and 64 did not report findings for critical outcomes. Fifteen studies were grouped to compare shifts24 hours versus shifts ≥24 hours. None of the findings for the critical outcomes of patient and personnel safety were categorized as unfavorable toward shorter duration shifts (24 hours). Nine studies were favorable toward shifts24 hours for at least one of the 7 important outcomes, while findings from one study were categorized as unfavorable. Evidence quality was low or very low.The quality of existing evidence on the impact of shift duration on fatigue and fatigue-related risks is low or very low. Despite these limitations, this systematic review suggests that for outcomes considered critical or important to EMS personnel, shifts24 hours in duration are more favorable than shifts ≥24 hours.

Administrators of Emergency Medical Services (EMS) operations lack guidance on how to mitigate workplace fatigue, which affects greater than half of all EMS personnel. The primary objective of the Fatigue in EMS Project was to create an evidence-based guideline for fatigue risk management tailored to EMS operations.Systematic searches were conducted from 1980 to September 2016 and guided by seven research questions framed in the Population, Intervention, Comparison, Outcome (PICO) framework. Teams of investigators applied inclusion criteria, which included limiting the retained literature to EMS personnel or similar shift worker groups. The expert panel reviewed summaries of the evidence based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The panel evaluated the quality of evidence for each PICO question separately, considered the balance between benefits and harms, considered the values and preferences of the targeted population, and evaluated the resource requirements/needs. The GRADE Evidence-to-Decision (EtD) Framework was used to prepare draft recommendations based on the evidence, and the Content Validity Index (CVI) was used to quantify the panel's agreement on the relevance and clarity of each recommendation. CVI scores for relevance and clarity were measured separately on a 1-4 scale to indicate consensus/agreement among panel members and conclusion of recommendation development.The EtD framework was applied to all 7 PICO questions, and the panel created 5 recommendations. PICO1: The panel recommends using fatigue/sleepiness survey instruments to measure and monitor fatigue in EMS personnel. PICO2: The panel recommends that EMS personnel work shifts shorter than 24 hours in duration. PICO3: The panel recommends that EMS personnel have access to caffeine as a fatigue countermeasure. PICO4: The panel recommends that, EMS personnel have the opportunity to nap while on duty to mitigate fatigue. PICO5: The panel recommends that EMS personnel receive education and training to mitigate fatigue and fatigue-related risks. The panel referenced insufficient evidence as the reason for making no recommendation linked to 2 PICO questions.Based on a review of the evidence, the panel developed a guideline with 5 recommendations for fatigue risk management in EMS operations.

The National Association of EMS Physicians (NAEMSP®) affirmed the core principles of EMS physician oversight in the position statement Physician Oversight of Emergency Medical Services (1). That do...

Prehospital ultrasound is not yet widely implemented. Most studies report on convenience samples and trauma patients, often by prehospital physicians or critical care clinicians. We assessed the feasibility of paramedic performed prehospital lung ultrasound in medical patients with respiratory distress.Paramedics at 2 ambulance stations in the city of Pittsburgh, Pennsylvania, USA underwent a 2-hour training session in prehospital lung ultrasound using the SonoSite iViz, a handheld ultrasound device. Emergency medical services (EMS) command center (EMS-CC) physicians were instructed in the interpretation of lung ultrasound images. Paramedics enrolled patients presenting with signs and symptoms of respiratory distress over a 3-month period. The ultrasound exam included anterior and lateral views from both sides of the chest. Images were transmitted wirelessly using a mobile hotspot device and uploaded into an online image archiving system. Images were interpreted remotely by the EMS-CC physicians, and 2 expert sonographers provided an overread. We assessed agreement between EMS-CC physicians and experts, as well as between chart-review derived ED diagnosis and both EMS-CC physician and expert interpretation. We defined four a priori hypotheses that would need to be met for the intervention to be considered "feasible."A total of 34 of 78 (43.6%) eligible patients had an ultrasound exam completed. Image transmission was successful in 25 (73.5%) of cases where ultrasound was performed. The primary reason for not enrolling an otherwise eligible patient was equipment failure (25.0%), followed by patient acuity and patient refusal (18.2% each). A total of 20 (58.8%) completed scans were deemed uninterpretable upon expert review. Agreement between EMS physicians and experts was poor. Agreement between EMS-CC physicians and ED diagnosis, as well as between experts and ED diagnosis, was fair. The predetermined thresholds for feasibility were not met.Paramedic performed prehospital lung ultrasound for patients with respiratory distress and remote interpretation by EMS physicians did not meet the predetermined thresholds to be considered "feasible" in a real-world environment with currently available technologies. This study identified important barriers to the implementation of prehospital lung ultrasound, which should be addressed in future studies.

To evaluate the association between total medical contact, prehospital, and emergency department delays in antibiotic administration and in-hospital mortality among patient encounters with community-acquired sepsis.Retrospective cohort study.Nine hospitals served by 21 emergency medical services agencies in southwestern Pennsylvania from 2010 through 2012.All emergency medical services encounters with community acquired sepsis transported to the hospital.Among 58,934 prehospital encounters, 2,683 had community-acquired sepsis, with an in-hospital mortality of 11%. Median time from first medical contact to antibiotic administration (total medical contact delay) was 4.2 hours (interquartile range, 2.7-8.0 hr), divided into a median prehospital delay of 0.52 hours (interquartile range, 0.40-0.66 hr) and a median emergency department delay of 3.6 hours (interquartile range, 2.1-7.5 hr). In a multivariable analysis controlling for other risk factors, total medical contact delay was associated with increased in-hospital mortality (adjusted odds ratio for death, 1.03 [95% CI, 1.00-1.05] per 1-hr delay; p0.01), as was emergency department delay (p = 0.04) but not prehospital delay (p = 0.61).Both total medical contact and emergency department delay in antibiotic administration are associated with in-hospital mortality in community-acquired sepsis.

Clinical heart failure (HF) occurs frequently after ST-segment elevation myocardial infarction (STEMI), and is associated with increased mortality. We assessed the impact of remote ischemic peri-conditioning (RIPC) during inter-facility air medical transport of STEMI patients on clinical HF following primary percutaneous coronary intervention (pPCI).Data from Acute Coronary Treatment and Intervention Outcomes Network Registry®-Get With the Guidelines™ (ACTION Registry-GWTG) from two PCI-hospitals that are utilizing RIPC during inter-facility helicopter transport of STEMI patients for pPCI between March, 2013 and September, 2015 were used for this study. The analyses were limited to inter-facility STEMI patients transported by helicopter with LVEF55% after pPCI. The outcome measures were occurrence of clinical HF and serum level of brain-type natriuretic peptide (BNP).Out of the 150 STEMI patients in this analysis, 92 patients received RIPC and 58 did not. The RIPC and non-RIPC groups were generally similar in demographic and clinical characteristics except for lower incidence of cardiac arrest in the RIPC group (3/92 [3.3%] versus 13/58 [22.4%], p=0.002). STEMI patients who received RIPC were less likely to have in-hospital clinical HF compared to patients who did not receive RIPC (3/92 [3.3%] versus 7/58 [12.1%]; adjusted OR=0.22, 95% CI 0.05-0.92, p=0.038) after adjusting for baseline differences. In subgroup analysis, RIPC was associated with lower BNP (123 [interquartile range, 17.0-310] versus 319 [interquartile range, 106-552], p=0.029).RIPC applied during inter-facility air transport of STEMI patients for pPCI is associated with reduced incidence of clinical HF and serum BNP.

Greater than half of Emergency Medical Services (EMS) personnel report work-related fatigue, yet there are no guidelines for the management of fatigue in EMS. A novel process has been established for evidence-based guideline (EBG) development germane to clinical EMS questions. This process has not yet been applied to operational EMS questions like fatigue risk management. The objective of this study was to develop content valid research questions in the Population, Intervention, Comparison, and Outcome (PICO) framework, and select outcomes to guide systematic reviews and development of EBGs for EMS fatigue risk management.We adopted the National Prehospital EBG Model Process and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for developing, implementing, and evaluating EBGs in the prehospital care setting. In accordance with steps one and two of the Model Process, we searched for existing EBGs, developed a multi-disciplinary expert panel and received external input. Panelists completed an iterative process to formulate research questions. We used the Content Validity Index (CVI) to score relevance and clarity of candidate PICO questions. The panel completed multiple rounds of question editing and used a CVI benchmark of ≥0.78 to indicate acceptable levels of clarity and relevance. Outcomes for each PICO question were rated from 1 = less important to 9 = critical.Panelists formulated 13 candidate PICO questions, of which 6 were eliminated or merged with other questions. Panelists reached consensus on seven PICO questions (n = 1 diagnosis and n = 6 intervention). Final CVI scores of relevance ranged from 0.81 to 1.00. Final CVI scores of clarity ranged from 0.88 to 1.00. The mean number of outcomes rated as critical, important, and less important by PICO question was 0.7 (SD 0.7), 5.4 (SD 1.4), and 3.6 (SD 1.9), respectively. Patient and personnel safety were rated as critical for most PICO questions. PICO questions and outcomes were registered with PROSPERO, an international database of prospectively registered systematic reviews.We describe formulating and refining research questions and selection of outcomes to guide systematic reviews germane to EMS fatigue risk management. We outline a protocol for applying the Model Process and GRADE framework to create evidence-based guidelines.

Objective To assess the impact of remote ischemic peri-conditioning (RIPC) during inter-facility air medical transport of ST-segment elevation myocardial infarction (STEMI) patients on the incidence of acute kidney injury (AKI) following primary percutaneous coronary intervention (pPCI). Background STEMI patients who receive pPCI have an increased risk of AKI for which there is no well-defined prophylactic therapy in the setting of emergent pPCI. Methods Using the ACTION Registry-GWTG, we evaluated the impact of RIPC applied during inter-facility helicopter transport of STEMI patients from non-PCI capable hospitals to 2 PCI-hospitals in the United States between March, 2013 and September, 2015 on the incidence of AKI following pPCI. AKI was defined as ≥0.3 mg/dL increase in creatinine within 48–72 hours after pPCI. Results Patients who received RIPC (n = 127), compared to those who did not (n = 92), were less likely to have AKI (11 of 127 patients [8.7%] vs. 17 of 92 patients [18.5%]; adjusted odds ratio = 0.32, 95% CI 0.12–0.85, P = 0.023) and all-cause in-hospital mortality (2 of 127 patients [1.6%] vs. 7 of 92 patients [7.6%]; adjusted odds ratio = 0.14, 95% CI 0.02–0.86, P = 0.034) after adjusting for socio-demographic and clinical characteristics. There was no difference in hospital length of stay (3 days [interquartile range, 2–4] vs. 3 days [interquartile range, 2–5], P = 0.357) between the 2 groups. Conclusion RIPC applied during inter-facility helicopter transport of STEMI patients for pPCI is associated with lower incidence of AKI and in-hospital mortality. The use of RIPC for renal protection in STEMI patients warrants further in depth investigation.

Fatigue in the Emergency Medical Services (EMS) workplace is widespread. Reports of fatigue-related events that involve ambulance crashes, personnel injury, patient death, and other negative outcom...

Background: Patients with acute illness who receive intravenous (IV) fluids prior to hospital arrival may have a lower in-hospital mortality. To better understand whether this is a direct treatment effect or epiphenomenon of downstream care, we tested the association between a prehospital fluid bolus and the change in inflammatory cytokines measured at prehospital and emergency department timepoints in a sample of non-trauma, non-cardiac arrest patients at risk for critical illness. Methods: In a prospective cohort study, we screened 4,013 non-trauma, non-cardiac arrest encounters transported by City of Pittsburgh Emergency Medical Services (EMS) to 2 hospitals from August 2013 to February 2014. In 345 patients, we measured prehospital biomarkers (IL-6, IL-10, and TNF) at 2 time points: the time of prehospital IV access placement by EMS and at ED arrival. We determined the relative change for marker X as: ([XED – XEMS]/XEMS). We determined the risk-adjusted association between prehospital IV fluid bolus and relative change for each marker using multivariable linear regression. Results: Among 345 patients, 88 (26%) received a prehospital IV fluid bolus and 257 (74%) did not. Compared to patients who did not receive prehospital fluids, median prehospital IL-6 was greater initially in subjects receiving a prehospital IV fluid bolus (22.3 [IQR 6.4–113] vs. 11.5 [IQR 5.5–47.6]). Prehospital IL-10 and TNF were similar in both groups (IL-10: 3.5 [IQR 2.2–25.6] vs. 3.0 [IQR 1.9–9.0]; TNF: 7.5 [IQR 6.4–10.4] vs. 6.9 [IQR 6.0–8.3]). After adjustment for demographics, illness severity, and prehospital transport time, we observed a relative decrease in IL-6 at hospital arrival in those receiving a prehospital fluid bolus (adjusted β = −10.0, 95% CI: −19.4, −0.6, p = 0.04), but we did not detect a significant change in IL-10 (p = 0.34) or TNF (p = 0.53). Conclusions: Among non-trauma, non-cardiac arrest patients at risk for critical illness, a prehospital IV fluid bolus was associated with a relative decrease in IL-6, but not IL-10 or TNF.

ObjectivesChest pain is among the leading causes for emergency medical services (EMS) activation. Acute myocardial infarction (MI) is not only one of the most critical aetiologies of chest pain, but also one of few conditions encountered by EMS that has been shown to follow a circadian pattern. Understanding the diurnal relationship between the inflow of chest pain patients and the likelihood of acute MI may inform prehospital and emergency department (ED) healthcare providers regarding the prediction, and hence prevention, of dire outcomes.MethodsThis was a secondary analysis of previously collected data from an observational prospective study that enrolled consecutive chest pain patients transported by a large metropolitan EMS system in the USA. We used the time of EMS call to determine the time-of-day of the indexed encounter. Two independent reviewers examined available medical data to determine our primary outcome, the presence of MI, and our secondary outcomes, infarct size and 30-day major adverse cardiac events (MACE). We estimated infarct size using peak troponin level.ResultsWe enrolled 2065 patients (age 56±17, 53% males, 7.5% with MI). Chest pain encounters increased from 9:00 AM to 2:00 PM, with a peak at 1:00 PM and a nadir at 6:00 AM. Acute MI had a bimodal distribution with two peaks: 10 AM in ST-elevation MI, and 10 PM in non-ST-elevation MI. ST-elevation MI with afternoon onset was an independent predictor of infarct size. Acute MI with winter and early spring presentation was an independent predictor of 30-day MACE.ConclusionsEMS-attended chest pain calls follow a diurnal pattern, with the most vulnerable patients encountered during afternoons and winter/spring seasons. These data can inform prehospital and ED healthcare providers regarding the time of presentation where patients are more likely to have an underlying MI and subsequently worse outcomes.

Scientific reports 9(0), 1315 (14 pages) (2019). doi:10.1038/s41598-018-37803-0, Published by Macmillan Publishers Limited, part of Springer Nature, [London]