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Introduction The COVID-19 pandemic may affect both use of 9–1-1 systems and prehospital treatment and transport practices. We evaluated EMS responses in an EMS region when it experienced low to moderate burden of COVID-19 disease to assess overall trends, response and management characteristics, and non-transport rates. Our goal is to inform current and future pandemic response in similar regions. Methods We performed a retrospective review of prehospital EMS responses from 22 urban, suburban, and rural EMS agencies in Western Pennsylvania. To account for seasonal variation, we compared demographic, response, and management characteristics for the 2-month period of March 15 to May 15, 2020 with the corresponding 2-month periods in 2016–2019. We then tested for an association between study period (pandemic vs historical control) and incidence of non-transport in unadjusted and adjusted regression. Finally, we described the continuous trends in responses and non-transports that occurred during the year before and initial phase of the COVID-19 pandemic from January 1, 2019 to May 31, 2020. Results Among 103,607 EMS responses in the 2-month comparative periods of March 15 to May 15, 2016–2020, we found a 26.5% [95% CI 26.9%, 27.1%] decrease in responses in 2020 compared to the same months from the four prior years. There was a small increase in respiratory cases (0.6% [95%CI 0.1%, 1.1%]) and greater frequency of abnormal vital signs suggesting a sicker patient cohort. There was a relative increase (46.6%) in non-transports between periods. The pandemic period was independently associated with an increase in non-transport (adjusted OR 1.68; 95%CI 1.59, 1.78). Among 177,194 EMS responses occurring in the year before and during the early period of the pandemic, between January 1, 2019, and May 31, 2020, we identified a 31% decrease in responses and a 48% relative increase in non-transports for April 2020 compared to the previous year's monthly averages. Conclusion Despite a low to moderate burden of infection during the initial period of the COVID-19 pandemic, we found a decline in overall EMS response volumes and an increase in the rate of non-transports independent of patient demographics and other response characteristics.

Coral bleaching has a profound impact on the health and function of reef ecosystems, but the metabolomic effects of coral bleaching are largely uncharacterized. Here, untargeted metabolomics was used to analyse pairs of adjacent Montipora capitata corals that had contrasting bleaching phenotypes during a severe bleaching event in 2015. When these same corals were sampled four years later while visually healthy, there was a strong metabolomic signature of bleaching history. This was primarily driven by betaine lipids from the symbiont, where corals that did not bleach were enriched in saturated lyso-betaine lipids. Immune modulator molecules were also altered by bleaching history in both the coral host and the algal symbiont, suggesting a shared role in partner choice and bleaching response. Metabolomics from a separate set of validation corals was able to predict the bleaching phenotype with 100% accuracy. Experimental temperature stress induced phenotype-specific responses, which magnified differences between historical bleaching phenotypes. These findings indicate that natural bleaching susceptibility is manifested in the biochemistry of both the coral animal and its algal symbiont. This metabolome difference is stable through time and results in different physiological responses to temperature stress. This work provides insight into the biochemical mechanisms of coral bleaching and presents a valuable new tool for resilience-based reef restoration.

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

Scientific reports 10, 14646 (2020). doi:10.1038/s41598-020-71500-1, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

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: Compared to day workers, shift workers face an elevated risk of cardiovascular disease. We reviewed the evidence to address the research question: Does acute exposure to shift work impact (blunt) the natural drop (dip) in Blood Pressure (BP) occurring during sleep and/or nighttime hours? (PROSPERO CRD42018110847). Methods: We performed a systematic review of five databases. We compared pooled estimates of mean BP stratified by periods of shift work, rest/leisure, and sleep, and evaluated the quality of evidence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Results: Our search covered 1/1/1980-10/24/2018 and yielded 1,636 records. Inter-rater agreement during screening was high (Kappa=0.87). We retained 44 studies described in 50 publications. We identified wide variation in shift worker type, shift schedules, and regularity of BP measurements. Most studies examined BP during one shift workday and one rest/leisure day. No study examined the impact of repeated exposure to shift work on the sleep-related dip in BP. Eighteen studies examined night shifts and one reported on BP during sleep post night shift. Compared to BP measured during shift work, BP measured during any sleep period separate from shift work was lower by 17.5 mmHg Systolic BP (95%CI 15.75, 19.27) and 15.4 mmHg lower for Diastolic BP (95%CI 14.38, 16.42) (p Conclusions: There is limited research exploring the acute and long-term impact of shift work on BP during sleep. The available evidence is heterogenous, low quality, and suggests that the mean dip in BP during sleep separate from shift work is not blunted.

OBJECTIVE Recent studies have shown an increase of C-reactive-protein (CRP) after exposure to zinc- and copper-containing welding fumes. The objective of this study was to determine the effects of exposure to zinc- and copper-containing welding fumes on leukocytes, their subtypes, and myeloperoxidase (MPO). METHODS Serum samples of male volunteers were examined after exposures to welding fumes in two settings: repeated exposure on 4 consecutive days for 6 hours and single exposures for different times (3, 4, 5 hours). RESULTS Neutrophil granulocyte and MPO levels showed increases 24 hours after single and repeated exposures for 6 hours similar to CRP increases reported in literature. Overall leukocyte levels and levels of monocytes and lymphocytes were not significantly affected. CONCLUSIONS This study indicates the involvement of neutrophil granulocytes in welding fume fever additional to mediator related effects.

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...

Feature-based molecular networking allows the generation of molecular networks for mass spectrometry data that can recognize isomers, incorporate relative quantification and integrate ion mobility data.Molecular networking has become a key method to visualize and annotate the chemical space in non-targeted mass spectrometry data. We present feature-based molecular networking (FBMN) as an analysis method in the Global Natural Products Social Molecular Networking (GNPS) infrastructure that builds on chromatographic feature detection and alignment tools. FBMN enables quantitative analysis and resolution of isomers, including from ion mobility spectrometry.

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.

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.

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...

Background Sleep deprivation is common in shift work occupations, including safety-sensitive occupations. While extending sleep prior to scheduled shifts (i.e., “banking sleep”) may be an intuitive strategy for fatigue mitigation, the evidence behind this strategy is unclear. Methods We performed a systematic review of literature retrieved in searches of four databases. We examined agreement between two independent screeners, abstracted key findings, reviewed and synthesized findings, and evaluated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The Cochrane Collaboration's risk of bias tool was used to evaluate bias of individual studies. We reported findings as prescribed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results Of the 3007 records screened, five met inclusion criteria. The inter-rater agreement for inclusion/exclusion was high (κ = 0.87). One study addressed patient safety outcomes. Four studies assessed the impact of banking sleep on performance, five assessed measures of acute fatigue, and three evaluated banking sleep on indicators of health. All five studies presented a very serious risk of bias and the quality of evidence was very low. Given these caveats, the findings, in aggregate, support banking sleep as a strategy to improve indicators of performance and acute fatigue. Conclusions This systematic review identifies gaps in research of shift workers on the efficacy of banking sleep as a fatigue risk management strategy. The available evidence supports banking sleep prior to shiftwork as a strategy for improved patient safety, performance, and reducing acute fatigue.

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

Study objective It is unknown whether regionalization of postarrest care by interfacility transfer to cardiac arrest receiving centers reduces mortality. We seek to evaluate whether treatment at a cardiac arrest receiving center, whether by direct transport or early interfacility transfer, is independently associated with long-term outcome. Methods We performed a retrospective cohort study including adults resuscitated from out-of-hospital cardiac arrest in southwestern Pennsylvania and neighboring Ohio, West Virginia, and Maryland, which includes approximately 5.7 million residents in urban, suburban, and rural counties. Patients were treated by 1 of 78 ground emergency medical services agencies or 2 air medical transport agencies between January 1, 2010, and November 30, 2014. Our primary exposures of interest were interfacility transfer to a cardiac arrest receiving center within 24 hours of arrest or any treatment at a cardiac arrest receiving center regardless of transfer status. Our primary outcome was vital status, assessed through December 31, 2014, with National Death Index records. We used unadjusted and adjusted survival analyses to test the independent association of cardiac arrest receiving center care, whether through direct or interfacility transport, on mortality. Results Overall, 5,217 cases were observed for 3,629 person-years, with 3,865 total deaths. Most patients (82%) were treated at 42 non–cardiac arrest receiving centers with median annual volume of 17 cases (interquartile range 1 to 53 cases per center annually), whereas 18% were cared for at cardiac arrest receiving centers receiving at least 1 interfacility transfer per month. In adjusted models, treatment at a cardiac arrest receiving center was independently associated with reduced hazard of death compared with treatment at a non–cardiac arrest receiving center (adjusted hazard ratio 0.84; 95% confidence interval 0.74 to 0.94). These effects were unchanged when analysis was restricted to patients brought from the scene to the treating hospital. No other hospital characteristic, including total out-of-hospital cardiac arrest patient volume and cardiac catheterization capabilities, independently predicted outcome. Conclusion Both early interfacility transfer to a cardiac arrest receiving center and direct transport to a cardiac arrest receiving center from the scene are independently associated with reduced mortality.

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.

Point-of-care ultrasound (POCUS) has been suggested as a useful tool to predict survival and guide interventions in out-of-hospital cardiac arrest (OHCA). While POCUS has been deployed in prehospital settings, a minimal amount of data exists on prehospital use, particularly by personnel with limited ultrasound experience. We aimed to characterize the feasibility and barriers to prehospital POCUS during OHCA by emergency medicine services (EMS) physicians in training.We deployed the SonoSite iViz portable ultrasound device for use by EMS physicians for OHCA in an urban EMS system. All physicians received POCUS education as part of their graduate medical training and were provided an instructional video on use of the SonoSite iViz device. POCUS use was limited to identifying cardiac motion during pulse checks, without interrupting resuscitation, and the results could be used to supplement management at the physicians' discretion. Data were recorded prospectively by saving images on the device and through a custom electronic form within the patient care report. The primary measure was the frequency of use of POCUS during OHCA. Secondarily, we characterized agreement by expert (ultrasound fellowship trained) faculty (using a kappa statistic) and identified reported barriers to the use of prehospital POCUS.From November 2016 to March 2017, 348 physician field responses were reviewed, including 127 cases of OHCA. There were 106 patients remaining in arrest on physician arrival, with 56 (52.8%) cases of POCUS use. Still or video images were recorded in 48 cases; video in 34 cases. From video images, agreement in identifying cardiac motion between the EMS physician and expert reviewer occurred in 91% of cases (K = 0.82). Reasons cited for not using POCUS included return of circulation soon before or after arrival, prioritizing clinical interventions, not having the ultrasound device, mechanical failure, and cessation of resuscitation per advanced directives.Use of POCUS by EMS physicians to detect cardiac activity in OHCA is feasible and correlates with expert interpretation. Several avoidable barriers were identified and should be considered in the future implementation of prehospital POCUS. Larger studies are needed to determine what role POCUS may play in prehospital cardiac arrest management.

Das Rauchen ist in Deutschland die groste vermeidbare Ursache fur fruhzeitigen Tod. Das Netzwerk „Aufklarung gegen Tabak“ (AGT) ist eine im Jahr 2012 in Deutschland gegrundete Initiative, bei der sich inzwischen in 14 Landern an circa 80 Medizinfakultaten uber 3500 Medizinstudierende, Arztinnen und Arzte ehrenamtlich engagieren. In diesem Beitrag stellt die Initiative AGT ihr Konzept, sowie Aktivitaten, Ziele und begleitende Studien vor. Auf Schulebene adressiert das Programm 10- bis 15-jahrige Sekundarschuler und -schulerinnen. Erganzend zu einem multimodalen Ansatz werden bei den Schulbesuchen moderne Medien wie Facemorphing-Apps eingesetzt, die nicht nur von Schulern (45.000 pro Jahr in 14 Landern), sondern insgesamt bereits von uber 500.000 Menschen genutzt werden. Die Wirksamkeit der schulbasierten Intervention wird in randomisierten Langzeitstudien mit aktuell 20.000 Jugendlichen in Deutschland untersucht. Eine erste Langzeitstudie zeigte Hinweise auf einen protektiven Effekt bezuglich Rauchbeginn, besonders bei Schulerinnen, niedrigem Bildungsniveau und vorhandenem Migrationshintergrund. An 13 (von 28 teilnehmenden) deutschen Medizinfakultaten bildet das Programm jahrlich mehrere hundert angehende Arztinnen und Arzte in wissenschaftlich konzipierten Wahlfachern fur die fundierte Entwohnung von Patienten aus und sensibilisiert sie fur die Tabakepidemie. Approbierte Mitglieder treten als „Arzteverband Tabakpravention“ mit lokalen Bundestagsabgeordneten in den Dialog. AGT motiviert die angehende Medizinergeneration, initial uber Pravention im Schulsetting, sich der Herausforderung der nationalen Tabakkontrolle auch auf hochschulpolitischer und bundespolitischer Ebene zu stellen.

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

Objective: Few areas of prehospital care are supported by evidence-based guidelines (EBGs). We aimed to identify gaps in clinical and operational prehospital EBGs to prioritize future EBG development and research funding. Methods: Using modified Delphi methodology, we sought consensus among experts in prehospital care and EBG development. Five rounds of surveys were administered between October 2019 and February 2020. Round 1 asked participants to list the top three gaps in prehospital clinical guidelines and top three gaps in operational guidelines that should be prioritized for guideline development and research funding. Based on responses, 3 reviewers performed thematic analysis to develop a list of prehospital EBG gaps, with participant feedback in Round 2. In Round 3, participants rated each gap's importance using a 5-point Likert scale, and participants' responses were averaged. In Round 4, participants rank-ordered 10 gaps with the highest mean scores identified in Round 3. In Round 5, participants indicated their agreement with sets of the highest ranked gaps. Results: Of 23 invited participants, 14 completed all 5 rounds. In Rounds 1 and 2, participants submitted 65 clinical and 58 operational gaps, and thematic analysis identified 23 unique clinical gaps and 28 unique operational gaps. The final prioritized list of clinical EBG gaps was: 1) airway management in adult and pediatric patients, 2) care of the pediatric patient, and 3) management of prehospital behavioral health emergencies, with 79% of participants agreeing. The final prioritized list of operational EBG gaps was: 1) define and measure the impact of EMS care on patient outcomes, 2) practitioner wellness, and 3) practitioner safety in the out-of-hospital environment, with 86% of participants agreeing. Conclusions: This modified Delphi study identifies gaps in prehospital EBGs that, if prioritized for development and research funding, would be expected to have the greatest impact on prehospital clinical care and operations.

International audience; Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.

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

The marine bacterial genus Pseudoalteromonas is known for their ability to produce antimicrobial compounds. The metabolite-producing capacity of Pseudoalteromonas has been associated with strain pigmentation, however, the genomic basis of their antimicrobial capacity remains to be explained. In this study, we sequenced the whole genome of six Pseudoalteromonas strains (three pigmented and three non-pigmented), with the purpose of identifying biosynthetic gene clusters (BGCs) associated to compounds we detected via microbial interactions along through MS-based molecular networking. The genomes were assembled and annotated using the SPAdes and RAST pipelines and mined for the identification of gene clusters involved in secondary metabolism using the antiSMASH database. Nineteen BGCs were detected for each non-pigmented strain, while more than thirty BGCs were found for two of the pigmented strains. Among these, the groups of genes of nonribosomal peptide synthetases (NRPS) that code for bromoalterochromides stand out the most. Our results show that all strains possess BGCs for the production of secondary metabolites, and a considerable number of distinct polyketide synthases (PKS) and NRPS clusters are present in pigmented strains. Furthermore, the molecular networking analyses revealed two new molecules produced during microbial interactions: the dibromoalterochromides D/D&rsquo, (11&ndash, 12).

Introduction HEART score is widely used to stratify patients with chest pain in the emergency department but has never been validated for cocaine-associated chest pain (CACP). We sought to evaluate the performance of HEART score in risk stratifying patients with CACP compared to an age- and sex-matched cohort with non-CACP. Methods The parent study was an observational cohort study that enrolled consecutive patients with chest pain. We identified patients with CACP and age/sex matched them to patients with non-CACP in 1:2 fashion. HEART score was calculated retrospectively from charts. The primary outcome was major adverse cardiac events (MACE) within 30 days of indexed encounter. Results We included 156 patients with CACP and 312 age-and sex-matched patients with non-CACP (n = 468, mean age 51 ± 9, 22% females). There was no difference in rate of MACE between the groups (17.9% vs. 15.7%, p = 0.54). Compared to the non-CACP group, the HEART score had lower classification performance in those with CACP (AUC = 0.68 [0.56–0.80] vs. 0.84 [0.78–0.90], p = 0.022). In CACP group, Troponin score had the highest discriminatory value (AUC = 0.72 [0.60–0.85]) and Risk factors score had the lowest (AUC = 0.47 [0.34–0.59]). In patients deemed low-risk by the HEART score, those with CACP were more likely to experience MACE (14% vs. 4%, OR = 3.7 [1.3–10.7], p = 0.016). Conclusion In patients with CACP, HEART score performs poorly in stratifying risk and is not recommended as a rule out tool to identify those at low risk of MACE.

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.

ObjectivesHigher 24-hour blood pressure (BP) and blunted BP dipping during sleep and night-time hours are associated with adverse health outcomes. Night shift work may affect 24-hour BP and dipping patterns, but empirical data in emergency medical services (EMS) clinician shift workers are sparse. We implemented ambulatory blood pressure monitoring (ABPM) in EMS workers to characterise BP during night shift work versus a non-workday, and sleep versus wake.MethodsParticipants worked night shifts. Hourly ABPM and wrist actigraphy (to measure sleep) were collected during two 24-hour periods, one scheduled night shift and one non-workday. Blunted BP dipping was defined as a BP decrease of ResultsOf 56 participants, 53 (53.6% female, mean age 26.5 (SD 7.5) years) completed the study. During daytime sleep on a workday, 49.1% of participants had blunted systolic BP (SBP) or diastolic BP (DBP) dipping. During night-time sleep on a non-workday, 25% had blunted SBP dipping and 3.9% blunted DBP dipping. Blunted SBP or DBP dipping occurred among all participants who did not nap during the night shift or who napped ConclusionsDuring night shift work, the BP dipping of EMS shift workers is blunted; however, most who nap for 60 min or longer experience a healthy dip in BP. The potential health consequences of these observations in EMS clinicians warrant further study.

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.

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.

Managing out-of-hospital cardiac arrest involves unique challenges, including delays in the initiation of advanced interventions and a limited number of trained personnel on scene. Recent out-of-hospital randomized controlled trials, systematic reviews, and metaanalyses provide key insights into what interventions are best proven to positively impact patient outcomes from out-of-hospital cardiac arrest. We review the literature on medications used in out-of-hospital cardiac arrest and summarize evidence-based guidelines from the American Heart Association that form the basis for most emergency medical services cardiac arrest protocols across the United States.

International audience; Infection is a risk for any intervention. In surgery, for example, pathogenic bacteria are found in more than 90% of operative wounds during closure. This exists whatever the surgical technique and whatever the environment (the laminar flow does not entirely eliminate this risk). These bacteria are few in number but can proliferate. They find in the operative wound a favourable environment (haematoma, ischaemia, modification of oxido-reduction potential...) and the intervention induces anomalies of the immune defences. In the case of the installation of foreign material, the risk is increased. The objective of antibiotic prophylaxis (ABP) is to prevent bacterial growth in order to reduce the risk of infection at the site of the intervention. The preoperative consultation represents a privileged moment to decide on the prescription of a ABP. It is possible to define the type of intervention planned, the associated risk of infection (and therefore the necessity or not of ABP), the time of prescription before surgery and any allergic antecedents which may modify the choice of the selected antibiotic molecule.

Airway device placement and maintenance are of utmost importance when managing critically ill patients. The best method to secure airway devices is currently unknown.We sought to determine the force required to dislodge 4 types of airways with and without airway securing devices.We performed a prospective study using 4 commonly used airway devices (endotracheal tube [ETT], laryngeal mask airway [LMA], King laryngeal tube [King], and iGel) performed on 5 different mannequin models. All devices were removed twice per mannequin in random order, once unsecured and once secured as per manufacturers' recommendations; Thomas Tube Holder (Laerdal, Stavanger, Norway) for ETT, LMA, and King; custom tube holder for iGel. A digital force measuring device was attached to the exposed end of the airway device and gradually pulled vertically and perpendicular to the mannequin until the tube had been dislodged, defined as at least 4 cm of movement. Dislodgement force was reported as the maximum force recorded during dislodgement. We compared the relative difference in the secured and unsecured force for each device and between devices using a random-effects regression model accounting for variability in the manikins.The median dislodgment forces (interquartile range [IQR]) in pounds for each secured device were: ETT 13.3 (11.6, 14.1), LMA 16.6 (13.9, 18.3), King 21.7 (16.9, 25.1), and iGel 8 (6.8, 8.3). The median dislodgement forces for each unsecured device were: ETT 4.5 (4.3, 5), LMA 8.4 (6.8, 10.7), King 10.6 (8.2, 11.5), and iGel 3.9 (3.2, 4.2). The relative difference in dislodgement forces (95% confidence intervals) were higher for each device when secured: ETT 8.6 (6.2 to 11), LMA 8.8 (4.6 to 13), King 12.1 (7.2 to 16.6), iGel 4 (1.1 to 6.9). When compared to secured ETT, the King required greater dislodgement force (relative difference 8.6 [4.5-12.7]). The secured iGel required less force than the secured ETT (relative difference -4.8 [-8.9 to -0.8]).Compared with a secured device, an unsecured airway device requires only half the force to cause airway dislodgement. The secured King had the highest dislodgement force relative to the other studied devices.

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.

Objective To develop and internally validate a metalearner algorithm to predict the hourly rate of emergency medical services (EMS) dispatches in an urban setting. Methods We performed an analysis of EMS data from New York City between years 2015-2019. Our outcome was hourly EMS dispatches, expressed as continuous data. Hours were split into derivation (75%) and validation (25%) datasets. Candidate variables included averages of prior rates, temporal and weather characteristics. We used a metalearner to evaluate and aggregate individual learners (generalized linear model, generalized additive model, random forest, multivariable adaptive regression splines, and extreme gradient boost). Four models were investigated: 1) temporal variables, 2) weather and temporal variables, and datasets in which weather data were lagged by 3) six and 4) twelve hours. In exploratory analyses, we constructed learners for high acuity and trauma encounters. Results 7,364,275 EMS dispatches occurred during the 43,823-hour period. When using temporal variables, the mean absolute error (MAE) rate was 11.5 dispatches in the validation dataset. These were slightly improved following incorporation of weather variables (MAE 11.3). When using 6- and 12-hour lagged weather variables, learners demonstrated lower accuracy (MAE 11.8 in 6-hour lagged datasets; 12.2 in 12-hour lagged dataset). All models had a coefficient of determination (R2) ≥0.91. The extreme gradient boosting and random forest learners were assigned the highest coefficients. In an investigation of variable importance, hour of day and average EMS dispatches over the previous six hours were the most important variables in both the extreme gradient boosting and random forest learners. The algorithm performed well at predicting frequently occurring peaks, with greater challenges at both extremes. Learners created high-acuity and for trauma-related encounters demonstrated superior MAE, but with lower R2 in the validation cohort (MAE 6.9 and R2 0.84 for high acuity encounters; MAE 5.3 and R2 0.79 for trauma in learners using time and weather variables). Conclusion We developed an ensemble machine learning algorithm to predict EMS dispatches in an urban setting. These models demonstrated high accuracy, with MAEs

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.

Resume La trompe d’Eustache (tube auditif) et les cavites tympanomastoidiennes forment un ensemble anatomique et fonctionnel difficilement dissociable, d’ou l’appellation « systeme tubotympanique ». L’etude de ce systeme a fait l’objet de nombreux travaux dont les resultats complexes et parfois contradictoires rendent difficile une vue d’ensemble de son fonctionnement. L’objectif cet article est d’en synthetiser les connaissances actuelles, prealable indispensable a la comprehension de son dysfonctionnement et notamment de la genese de l’otite chronique. L’ensemble du systeme est tapisse par une muqueuse qui en assure la continuite, bien qu’elle comporte certaines particularites selon la zone concernee, et y joue un role primordial. Ainsi, dans des conditions physiologiques, la diffusion gazeuse a travers la muqueuse tympanomastoidienne assure l’essentiel de l’equilibre pressionnel regnant entre l’oreille moyenne (OM) et le monde exterieur, l’ouverture tubaire n’intervenant que tres peu. Lors des changements rapides et importants de la pression atmospherique, la fonction ventilatoire de la trompe est alors mise en jeu, sous l’effet d’un mecanisme reflexe. Le systeme possede en outre d’autres fonctions indispensables au bon fonctionnement de l’OM, une fonction de protection vis-a-vis des secretions et agents pathogenes en provenance du rhinopharynx, mais aussi de certains bruits physiologiques, une fonction de clairance des cavites de l’OM dependant du transport mucociliaire des pathogenes, liee en partie a la secretion des glandes sous-muqueuses et une fonction de defense immunitaire.

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.

A board review question bank was created to assist candidates in their preparation for the 2015 EMS certification examination. We aimed to describe the development of this question bank and evaluate its successes in preparing candidates to obtain EMS subspecialty board certification.An online question bank was developed by 13 subject matter experts who participated as item writers, representing eight different EMS fellowship programs. The online question bank consisted of four practice tests, with each of the tests comprised of 100 questions. The number of candidates who participated in and completed the question bank was calculated. The passing rate among candidates who completed the question bank was calculated and compared to the publicly reported statistics for all candidates. The relationship between candidates' performance on the question bank and subspecialty exam pass rates was determined.A total of 252 candidates took at least one practice test and, of those, 225 candidates completed all four 100-question practice tests. The pass rate on the 2015 EMS certification exam was 79% (95%CI 74-85%) among candidates who completed the question bank, which is 12% higher than the overall pass rate (p = 0.003). Candidates' performance on the question bank was positively associated with overall success on the exam (XCompleting the question bank program was associated with improved pass rates on the EMS certification exam. Strong performance on the question bank correlated with success on the exam.

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.

Resume Introduction Les nocardioses sont rares, de diagnostic clinique et microbiologique difficile, avec une morbi-mortalite importante, et surviennent souvent sur terrain debilite. Peu de donnees existent en France. Methodes Etude retrospective monocentrique de 2002 a 2014 incluant tous les patients avec au moins un prelevement microbiologique positif a Nocardia. Resultats Dix-neuf patients, dont 15 hommes, ont ete inclus, d’âge moyen 58 ans (25–85). Dix-sept presentaient un terrain a risque (pathologies pulmonaires 13, corticotherapie 12, tumeurs 2, infection par le VIH 2, diabete 3, greffe renale 2, lymphopenie 1). On denombre 12 infections pulmonaires, 3 infections cerebrales, 2 infections cutanees, 1 infection ganglionnaire, et 1 infection corneenne. La croissance souvent lente du germe conduit a un delai median de resultat de 35 jours (3–95). Neuf especes ont ete retrouvees. Quinze patients (79 %) ont recu une ou plusieurs lignes antibiotiques comprenant entre autres : cotrimoxazole (n = 9), amoxicilline (n = 7) cefotaxime/ceftriaxone (n = 7), imipeneme (n = 3) ou amikacine (n = 3). La duree moyenne de l’antibiotherapie etait de 207 jours. Quatre patients n’ont pas recu d’antibiotiques a cause d’un resultat tardif ou d’une co-infection bacterienne masquant la nocardiose. On deplore 5 deces (26 %) dont 2 imputables a une atteinte cerebrale. Six patients ont gueri, 4 ont rechute, l’evolution est inconnue pour 4, et 1 est encore en cours de traitement. Conclusion La prise en charge des nocardioses est compliquee. Une meilleure connaissance de celles-ci par une etude clinico-microbiologique nationale semble necessaire.

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.