Dispatch Categories as Indicators of Out-of-Hospital Time Critical Interventions and Associated Emergency Department Outcomes.

OBJECTIVES: Emergency medical services (EMS) systems increasingly grapple with rising call volumes and workforce shortages, forcing systems to decide which responses may be delayed. Limited research has linked dispatch codes, on-scene findings, and emergency department (ED) outcomes. This study evaluated the association between dispatch categorizations and time-critical EMS responses defined by prehospital interventions and ED outcomes. Secondarily, we proposed a framework for identifying dispatch categorizations that are safe or unsafe to hold in queue. METHODS: This retrospective, multi-center analysis encompassed all 9-1-1 responses from 8 accredited EMS systems between 1/1/2021 and 06/30/2023, utilizing the Medical Priority Dispatch System (MPDS). Independent variables included MPDS Protocol numbers and Determinant levels. EMS treatments and ED diagnoses/dispositions were categorized as time-critical using a multi-round consensus survey. The primary outcome was the proportion of EMS responses categorized as time-critical. A non-parametric test for trend was used to assess the proportion of time-critical responses Determinant levels. Based on group consensus, Protocol/Determinant level combinations with at least 120 responses (∼1 per week) were further categorized as safe to hold in queue (<1% time-critical intervention by EMS and <5% time-critical ED outcome) or unsafe to hold in queue (>10% time-critical intervention by EMS or >10% time-critical ED outcome). RESULTS: Of 1,715,612 EMS incidents, 6% (109,250) involved a time-critical EMS intervention. Among EMS transports with linked outcome data (543,883), 12% had time-critical ED outcomes. The proportion of time-critical EMS interventions increased with Determinant level (OMEGA: 1%, ECHO: 38%, p-trend < 0.01) as did time-critical ED outcomes (OMEGA: 3%, ECHO: 31%, p-trend < 0.01). Of 162 unique Protocols/Determinants with at least 120 uses, 30 met criteria for safe to hold in queue, accounting for 8% (142,067) of incidents. Meanwhile, 72 Protocols/Determinants met criteria for unsafe to hold, accounting for 52% (883,683) of incidents. Seven of 32 ALPHA level Protocols and 3/17 OMEGA level Protocols met the proposed criteria for unsafe to hold in queue. CONCLUSIONS: In general, Determinant levels aligned with time-critical responses; however, a notable minority of lower acuity Determinant level Protocols met criteria for unsafe to hold. This suggests a more nuanced approach to dispatch prioritization, considering both Protocol and Determinant level factors.

Racial, Ethnic, and Socioeconomic Disparities in Out-of-Hospital Pain Management for Patients With Long Bone Fractures.

STUDY OBJECTIVE: To evaluate racial and ethnic disparities in out-of-hospital analgesic administration, accounting for the influence of clinical characteristics and community socioeconomic vulnerability, among a national cohort of patients with long bone fractures. METHODS: Using the 2019-2020 ESO Data Collaborative, we retrospectively analyzed emergency medical services (EMS) records for 9-1-1 advanced life support transport of adult patients diagnosed with long bone fractures at the emergency department. We calculated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for out-of-hospital analgesic administration by race and ethnicity, accounting for age, sex, insurance, fracture location, transport time, pain severity, and scene Social Vulnerability Index. We reviewed a random sample of EMS narratives without analgesic administration to identify whether other clinical factors or patient preferences could explain differences in analgesic administration by race and ethnicity. RESULTS: Among 35,711 patients transported by 400 EMS agencies, 81% were White, non-Hispanic, 10% were Black, non-Hispanic, and 7% were Hispanic. In crude analyses, Black, non-Hispanic patients with severe pain were less likely to receive analgesics compared with White, non-Hispanic patients (59% versus 72%; Risk Difference: -12.5%, 95% CI: -15.8% to -9.9%). After adjustment, Black, non-Hispanic patients remained less likely to receive analgesics compared with White, non-Hispanic patients (aOR:0.65, 95% CI:0.53 to 0.79). Narrative review identified similar rates of patients declining analgesics offered by EMS and analgesic contraindications across racial and ethnic groups. CONCLUSIONS: Among EMS patients with long bone fractures, Black, non-Hispanic patients were substantially less likely to receive out-of-hospital analgesics compared with White, non-Hispanic patients. These disparities were not explained by differences in clinical presentations, patient preferences, or community socioeconomic conditions.

Prehospital Sepsis Recognition and Outcomes for Patients with Sepsis by Race and Ethnicity.

BACKGROUND: First medical contact for patients with sepsis often initiates in the prehospital setting, yet limited studies have explored the EMS sepsis recognition-mortality relationship. Racial and ethnic minority patients often have worse sepsis outcomes, yet the role of prehospital recognition in this inequity has not been explored. Our objective was to describe prehospital sepsis recognition and hospital mortality, with analysis by patient race and ethnicity. METHODS: Using linked EMS and hospital records from the 2021 ESO Data Collaborative, we retrospectively analyzed 9-1-1 EMS transports for adult patients with emergency department ICD-10 sepsis diagnosis codes. EMS sepsis recognition was defined as a primary or secondary sepsis impression, use of an electronic health record specialty sepsis form, or a prehospital sepsis alert. We used multivariable logistic regression to assess the association between EMS sepsis recognition and hospital mortality, adjusting for age, sex, race and ethnicity, scene socioeconomic status, and documented clinical characteristics: altered mental status, hypotension, tachypnea, tachycardia, fever. We conducted a secondary analysis of patients who were positive for the quick sequential organ failure assessment (qSOFA) using first prehospital vital signs. RESULTS: We analyzed 20,172 records for EMS-transported patients with diagnosed sepsis. Overall, 8% of patients were Black, 8% were Hispanic, and 72% were White. Prehospital sepsis recognition was 18%. Prehospital sepsis recognition was similar across racial and ethnic groups (Black: 17.2%, Hispanic: 17.4%, White: 18.1%) and adjusted odds of sepsis recognition did not differ between racial and ethnic groups. Overall mortality was 11% (2,186). Prehospital sepsis recognition was associated with a 18% reduction in adjusted odds of mortality (OR: 0.82, 95% CI: 0.70-0.94). Of patients who were qSOFA positive in the field (n = 2,168), EMS sepsis recognition was 32% and was similar across race and ethnicities. Adjusted odds of mortality were 0.68 (95% CI: 0.53-0.88) when sepsis was recognized in the prehospital setting. CONCLUSION: EMS identified sepsis in fewer than one in three patients even after limiting to those positive for qSOFA, without differences by race and ethnicity. EMS sepsis recognition was associated with reduced odds of mortality; however, Black patients remained at greater odds of death suggesting additional factors that warrant investigation.

Patient Outcomes Based on the 2011 CDC Guidelines for Field Triage of Injured Patients.

BACKGROUND: The Centers for Disease Control and Prevention Guidelines for Field Triage of Injured Patients drive the destination decision for millions of emergency medical services (EMS)-transported trauma patients annually, yet limited information exists regarding performance and relationship with patient outcomes as a whole. OBJECTIVE: To evaluate the association of positive findings on Centers for Disease Control and Prevention Guidelines for Field Triage of Injured Patients with hospitalization and mortality. METHODS: This retrospective study included all 911 responses from the 2019 ESO Data Collaborative research dataset with complete Centers for Disease Control and Prevention Guidelines for Field Triage of Injured Patients and linked emergency department dispositions, excluding children and cardiac arrests prior to EMS arrival. Patients were categorized by Centers for Disease Control and Prevention Guidelines for Field Triage of Injured Patients step(s) met. Outcomes were hospitalization and emergency department or inhospital mortality. RESULTS: There were 86,462 records included: n = 65,967 (76.3%) met no criteria, n = 16,443 (19.0%) met one step (n = 1,571 [9.6%] vitals, n = 1,030 [6.3%] anatomy of injury, n = 993 [6.0%] mechanism of injury, and n = 12,849 [78.1%] special considerations), and n = 4,052 (4.7%) met multiple. Compared with meeting no criteria, hospitalization odds increased threefold for vitals (odds ratio [OR]: 3.07, 95% confidence interval [CI]: 2.77-3.40), fourfold for anatomy of injury (OR: 3.94, 95% CI: 3.48-4.46), twofold for mechanism of injury (OR: 2.00, 95% CI: 1.74-2.29), or special considerations (OR: 2.46, 95% CI: 2.36-2.56). Hospitalization odds increased ninefold when positive in multiple steps (OR: 8.97, 95% CI: 8.37-9.62). Overall, n = 84,473 (97.7%) had mortality data available, and n = 886 (1.0%) died. When compared with meeting no criteria, mortality odds increased 10-fold when positive in vitals (OR: 9.58, 95% CI: 7.30-12.56), twofold for anatomy of injury (OR: 2.34, 95% CI: 1.28-4.29), or special considerations (OR: 2.10, 95% CI: 1.71-2.60). There was no difference when only positive for mechanism of injury (OR: 0.22, 95% CI: 0.03-1.54). Mortality odds increased 23-fold when positive in multiple steps (OR: 22.7, 95% CI: 19.7-26.8). CONCLUSIONS: Patients meeting multiple Centers for Disease Control and Prevention Guidelines for Field Triage of Injured Patients steps were at greater risk of hospitalization and death. When meeting only one step, anatomy of injury was associated with greater risk of hospitalization; vital sign criteria were associated with greater risk of mortality.

Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas.

BACKGROUND: Anti-CD19 chimeric antigen receptor T-cell immunotherapy (CAR-T) is now a standard treatment of relapsed or refractory B-cell non-Hodgkin lymphomas; however, a significant portion of patients do not respond to CAR-T and/or experience toxicities. Lymphodepleting chemotherapy is a critical component of CAR-T that enhances CAR-T-cell engraftment, expansion, cytotoxicity, and persistence. We hypothesized that the lymphodepletion regimen might affect the safety and efficacy of CAR-T. PATIENTS AND METHODS: We compared the safety and efficacy of lymphodepletion using either fludarabine/cyclophosphamide (n = 42) or bendamustine (n = 90) before tisagenlecleucel in two cohorts of patients with relapsed or refractory large B-cell lymphomas treated consecutively at three academic institutions in the United States (University of Pennsylvania, n = 90; Oregon Health & Science University, n = 35) and Europe (University of Vienna, n = 7). Response was assessed using the Lugano 2014 criteria and toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and, when possible, the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. RESULTS: Fludarabine/cyclophosphamide led to more profound lymphocytopenia after tisagenlecleucel infusion compared with bendamustine, although the efficacy of tisagenlecleucel was similar between the two groups. We observed significant differences, however, in the frequency and severity of adverse events. In particular, patients treated with bendamustine had lower rates of cytokine release syndrome and neurotoxicity. In addition, higher rates of hematological toxicities were observed in patients receiving fludarabine/cyclophosphamide. Bendamustine-treated patients had higher nadir neutrophil counts, hemoglobin levels, and platelet counts, as well as a shorter time to blood count recovery, and received fewer platelet and red cell transfusions. Fewer episodes of infection, neutropenic fever, and post-infusion hospitalization were observed in the bendamustine cohort compared with patients receiving fludarabine/cyclophosphamide. CONCLUSIONS: Bendamustine for lymphodepletion before tisagenlecleucel has efficacy similar to fludarabine/cyclophosphamide with reduced toxicities, including cytokine release syndrome, neurotoxicity, infectious and hematological toxicities, as well as reduced hospital utilization.

Histopathologic features predictive of metastasis and survival in 230 patients with cutaneous squamous cell carcinoma of the head and neck and non-head and neck locations: a single-center retrospective study.

BACKGROUND: Staging systems for cutaneous squamous cell carcinoma (cSCC) produce inconsistent risk stratification. OBJECTIVE: The aim of this study was to identify further prognostic parameters for better stratification. METHODS: We retrospectively analysed the prognostic significance of clinicopathologic parameters of 230 patients who underwent primary excision of invasive cSCC of the head and neck (n = 115) and non-head and non-neck (n = 115) locations. In addition to known high-risk features, we analysed tumour nest shape, invasion pattern, lymphoid response pattern and tumour budding. RESULTS: On multivariable analysis, lymphovascular invasion (LVI) and high tumour budding predicted worse disease-specific survival, and ulceration, LVI and high tumour budding predicted worse overall survival. Only ulceration was independently associated with risk of nodal metastasis. CONCLUSION: High tumour budding, LVI and ulceration are independently associated with poor outcome in cSCC and may be used to refine cSCC prognostic stratification, which is crucial to optimize clinical decision and to identify patients who are more likely to benefit from more aggressive interventions or clinical trials.

Implementation Evaluation of a Complex Intervention to Improve Timeliness of Care for Veterans with Transient Ischemic Attack.

BACKGROUND: The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurologic Symptoms (PREVENT) program was designed to address systemic barriers to providing timely guideline-concordant care for patients with transient ischemic attack (TIA). OBJECTIVE: We evaluated an implementation bundle used to promote local adaptation and adoption of a multi-component, complex quality improvement (QI) intervention to improve the quality of TIA care Bravata et al. (BMC Neurology 19:294, 2019). DESIGN: A stepped-wedge implementation trial with six geographically diverse sites. PARTICIPANTS: The six facility QI teams were multi-disciplinary, clinical staff. INTERVENTIONS: PREVENT employed a bundle of key implementation strategies: team activation; external facilitation; and a community of practice. This strategy bundle had direct ties to four constructs from the Consolidated Framework for Implementation Research (CFIR): Champions, Reflecting & Evaluating, Planning, and Goals & Feedback. MAIN MEASURES: Using a mixed-methods approach guided by the CFIR and data matrix analyses, we evaluated the degree to which implementation success and clinical improvement were associated with implementation strategies. The primary outcomes were the number of completed implementation activities, the level of team organization and > 15 points improvement in the Without Fail Rate (WFR) over 1 year. KEY RESULTS: Facility QI teams actively engaged in the implementation strategies with high utilization. Facilities with the greatest implementation success were those with central champions whose teams engaged in planning and goal setting, and regularly reflected upon their quality data and evaluated their progress against their QI plan. The strong presence of effective champions acted as a pre-condition for the strong presence of Reflecting & Evaluating, Goals & Feedback, and Planning (rather than the other way around), helping to explain how champions at the +2 level influenced ongoing implementation. CONCLUSIONS: The CFIR-guided bundle of implementation strategies facilitated the local implementation of the PREVENT QI program and was associated with clinical improvement in the national VA healthcare system. TRIAL REGISTRATION: clinicaltrials.gov: NCT02769338.

Approaches to screening for hyperglycaemia in pregnant women during and after the COVID-19 pandemic.

AIM: To evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA1c , during the COVID-19 pandemic. METHODS: Retrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004-2008; 826 consecutive gestational diabetes pregnancies, 2014-2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large-for-gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver-operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA1c performance. RESULTS: Gestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks [area under the receiver-operating characteristic curve for both criteria 0.81 (95% CI 0.79-0.83)], fasting plasma glucose [National Institute of Health and Clinical Excellence: area under the receiver-operating characteristic curve 0.75 (95% CI 0.65-0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver-operating characteristic curve 0.92 (95% CI 0.85-0.98)] and HbA1c at 28 weeks' gestation [National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75-0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77-0.91)]. Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2-5.4 mmol/l (sensitivity 18-41%; specificity 97-98%). CONCLUSIONS: Random plasma glucose at 12 weeks, and fasting plasma glucose or HbA1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available.

Out-of-Hospital Ketamine: Indications for Use, Patient Outcomes, and Associated Mortality.

STUDY OBJECTIVE: To describe out-of-hospital ketamine use, patient outcomes, and the potential contribution of ketamine to patient death. METHODS: We retrospectively evaluated consecutive occurrences of out-of-hospital ketamine administration from January 1, 2019 to December 31, 2019 reported to the national ESO Data Collaborative (Austin, TX), a consortium of 1,322 emergency medical service agencies distributed throughout the United States. We descriptively assessed indications for ketamine administration, dosing, route, transport disposition, hypoxia, hypercapnia, and mortality. We reviewed cases involving patient death to determine whether ketamine could be excluded as a potential contributing factor. RESULTS: Indications for out-of-hospital ketamine administrations in our 11,291 patients were trauma/pain (49%; n=5,575), altered mental status/behavioral indications (34%; n=3,795), cardiovascular/pulmonary indications (13%; n=1,454), seizure (2%; n=248), and other (2%; n=219). The highest median dose was for altered mental status/behavioral indications at 3.7 mg/kg (interquartile range, 2.2 to 4.4 mg/kg). Over 99% of patients (n=11,274) were transported to a hospital. Following ketamine administration, hypoxia and hypercapnia were documented in 8.4% (n=897) and 17.2% (n=1,311) of patients, respectively. Eight on-scene and 120 in-hospital deaths were reviewed. Ketamine could not be excluded as a contributing factor in 2 on-scene deaths, representing 0.02% (95% confidence interval 0.00% to 0.07%) of those who received out-of-hospital ketamine. Among those with in-hospital data, ketamine could not be excluded as a contributing factor in 6 deaths (0.3%; 95% confidence interval 0.1% to 0.7%). CONCLUSION: In this large sample, out-of-hospital ketamine was administered for a variety of indications. Patient mortality was rare. Ketamine could not be ruled out as a contributing factor in 8 deaths, representing 0.07% of those who received ketamine.

Initial Prehospital Rapid Emergency Medicine Score (REMS) as a Predictor of Patient Outcomes.

Background: A standardized objective measure of prehospital patient risk of hospitalization or death is needed. The Rapid Emergency Medicine Score (REMS), a validated risk-stratification tool, has not been widely tested for prehospital use. This study's objective was to assess predictive characteristics of initial prehospital REMS for ED disposition and overall patient mortality. Methods: This retrospective analysis used linked prehospital and hospital data from the national ESO Data Collaborative. All 911 responses from 1/1/2019-12/31/2019 were included. REMS (0-26) was calculated using age and first prehospital values for: pulse rate, mean arterial pressure, respiratory rate, oxygen saturation, and Glasgow Coma Scale. Non-transports, patients <18 and cardiac arrests prior to EMS arrival were excluded. The primary outcome was ED disposition, dichotomized to discharge versus admission, transfer, or death. The secondary outcome was overall survival to discharge (ED or inpatient). Transfers and records without inpatient disposition were excluded from the secondary analysis. Predictive ability was assessed using area under the receiver operating curve (AUROC). Optimal REMS cut points were determined using test characteristic curves. Univariable logistic regression modeling was used to quantify the association between initial prehospital REMS and each outcome. Results: Of 579,505 eligible records, 94,640 (16%) were excluded due to missing data needed to calculate REMS. Overall, 62% (n = 298,223) of patients were discharged from the ED, 36% (n = 175,212) were admitted, 2% (n = 10,499) were transferred, and 0.2% (n = 931) died in the ED. A REMS of 5 or lower demonstrated optimal statistical prediction for ED discharge versus not discharged (admission/transfer/death) (AUROC: 0.68). Patients with initial prehospital REMS of 5 or lower showed a three-fold increase in odds of ED discharge (OR: 3.28, 95%CI: 3.24-3.32). Of the 457,226 patients included in overall mortality analysis, >98% (n = 450,112) survived. AUROC of initial prehospital REMS for overall mortality was 0.79. A score 7 or lower was statistically optimal for predicting survival. Initial prehospital REMS of 7 or lower was associated with a five-fold increase in odds of overall survival (OR:5.41, 95%CI:5.15-5.69). Conclusion: Initial prehospital REMS was predictive of ED disposition and overall patient mortality, suggesting value as a risk-stratification measure for EMS agencies, systems and researchers.

The Cincinnati Prehospital Stroke Scale Compared to Stroke Severity Tools for Large Vessel Occlusion Stroke Prediction.

BACKGROUND: Various screening tools, ranging in complexity, have been developed to predict large vessel occlusion (LVO) stroke in the prehospital setting. Our objective was to determine whether newly-developed LVO stroke scales offer a clinically-meaningful advantage over the Cincinnati Prehospital Stroke Scale (CPSS). METHODS: We retrospectively analyzed prehospital patient care records linked with hospital data from 151 EMS agencies in the United States, between January 1, 2018 and December 31, 2018. We compared the CPSS to the Rapid Arterial Occlusion Evaluation (RACE), Los Angeles Motor Scale (LAMS), and the Vision, Aphasia, Neglect (VAN) assessment for LVO prediction. For each stroke scale, we used the intersection of sensitivity and specificity curves to determine optimal prediction cut-points. We used area under the ROC curve and 95% confidence intervals to assess for differences in discriminative ability between scales. RESULTS: We identified 13,596 prehospital records with one or more documented stroke scales of interest. Among these, 4,228 patients were diagnosed with stroke. Over half (57%, n = 2,415) of patients diagnosed with stroke experienced an acute ischemic stroke. Of patients with ischemic stroke, 26% (n = 628) were diagnosed with LVO. A CPSS score of 2 or higher demonstrated sensitivity = 69% and specificity = 78% for LVO. A RACE score of 4 or higher demonstrated sensitivity = 63%, specificity = 73%. A LAMS score of 3 or higher demonstrated sensitivity = 63%, specificity = 72% and a positive VAN score demonstrated sensitivity = 86%, specificity = 65%. Comparing the area under the ROC curve for each scale revealed no statistically significant differences in discriminative ability for LVO stroke. CONCLUSIONS: In this large sample of real-world prehospital patient encounters, the CPSS demonstrated similar predictive performance characteristics compared to the RACE, LAMS, and VAN for detecting LVO stroke. Prior to implementing a specific screening tool, EMS agencies should evaluate ease of use and associated implementation costs. Scored 0-3, the simple, widely-used CPSS may serve as a favorable prehospital screening instrument for LVO detection with a cut-point of 2 or higher maximizing the tradeoff between sensitivity and specificity.

COVID-19 Preliminary Case Series: Characteristics of EMS Encounters with Linked Hospital Diagnoses.

BACKGROUND: Few studies have examined the prehospital presentation, assessment, or treatment of patients diagnosed with coronavirus disease 2019 (COVID-19). The objective of this preliminary report is to describe prehospital encounters for patients with a COVID-19 hospital diagnosis and/or COVID-19 EMS suspicion versus those with neither a hospital diagnosis nor EMS suspicion of the disease. METHODS: This case series evaluated electronic patient care records from EMS agencies participating in a large national bi-directional data exchange. All records for 9-1-1 responses between March 1 and April 19, 2020, resulting in transport to a hospital, with at least one ICD-10 outcome returned via the data exchange were included. Hospital ICD-10 codes used to determine COVID-19 diagnoses included B97.2, B97.21, B97.29, B34.2, and U07.1. COVID-19 EMS suspicion was defined as a documented EMS primary or secondary impression of COVID-19, or indication of COVID-19 suspicion in the prehospital free-text narrative. Comparisons were stratified by COVID-19 hospital diagnosis and COVID-19 EMS suspicion. Descriptive and comparative statistics are presented. RESULTS: There were 84,540 EMS patient records with linked hospital ICD-10 codes included. Of those, 814 (1%) patients had a COVID-19 hospital diagnosis. Overall, COVID-19 EMS suspicion was documented for 3,204 (4%) patients. A COVID-19 EMS suspicion was documented for 636 (78%) of hospital diagnosed COVID-19 patients. Those with COVID-19 hospital diagnoses were more likely to present with tachycardia, tachypnea, hypoxia, and fever during the EMS encounter. EMS responses for patients diagnosed with COVID-19 were also more likely to originate from a skilled nursing/assisted living facility. EMS PPE (eye protection, mask, or gown) use was more frequently documented on records of patients who had hospital diagnosed COVID-19. CONCLUSION: In this large sample of prehospital encounters, EMS COVID-19 suspicion demonstrated sensitivity of 78% and positive predictive value of 20% compared with hospital ICD-10 codes. These data indicate that EMS suspicion alone is insufficient to determine appropriate utilization of PPE.

Inhibition of Epstein-Barr Virus Replication in Human Papillomavirus-Immortalized Keratinocytes.

Epstein-Barr virus (EBV) is implicated in the pathogenesis of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OSCC). EBV-associated cancers harbor a latent EBV infection characterized by a lack of viral replication and the expression of viral oncogenes. Cellular changes promoted by HPV are comparable to those shown to facilitate EBV latency, though whether HPV-positive cells support a latent EBV infection has not been demonstrated. Using a model of direct EBV infection into HPV16-immortalized tonsillar cells grown in organotypic raft culture, we showed robust EBV replication in HPV-negative rafts but little to no replication in HPV-immortalized rafts. The reduced EBV replication was independent of immortalization, as human telomerase-immortalized normal oral keratinocytes supported robust EBV replication. Furthermore, we observed reduced EBV lytic gene expression and increased expression of EBER1, a noncoding RNA highly expressed in latently infected cells, in the presence of HPV. The use of human foreskin keratinocyte rafts expressing the HPV16 E6 and/or E7 oncogene(s) (HPV E6 and E7 rafts) showed that E7 was sufficient to reduce EBV replication. EBV replication is dependent upon epithelial differentiation and the differentiation-dependent expression of the transcription factors KLF4 and PRDM1. While KLF4 and PRDM1 levels were unaltered, the expression levels of KLF4 transcriptional targets, including late differentiation markers, were reduced in HPV E6 and E7 rafts compared to their levels in parental rafts. However, the HPV E7-mediated block in EBV replication correlated with delayed expression of early differentiation markers. Overall, this study reveals an HPV16-mediated block in EBV replication, through E7, that may facilitate EBV latency and long-term persistence in the tumor context.IMPORTANCE Using a model examining the establishment of EBV infection in HPV-immortalized tissues, we showed an HPV-induced interruption of the normal EBV life cycle reminiscent of a latent EBV infection. Our data support the notion that a persistent EBV epithelial infection depends upon preexisting cellular alterations and suggest the ability of HPV to promote such changes. More importantly, these findings introduce a model for how EBV coinfection may influence HPV-positive (HPV-pos) OSCC pathogenesis. Latently EBV-infected epithelial cells, as well as other EBV-associated head-and-neck carcinomas, exhibit oncogenic phenotypes commonly seen in HPV-pos OSCC. Therefore, an HPV-induced shift in the EBV life cycle toward latency would not only facilitate EBV persistence but also provide additional viral oncogene expression, which can contribute to the rapid progression of HPV-pos OSCC. These findings provide a step toward defining a role for EBV as a cofactor in HPV-positive oropharyngeal tumors.

Asymmetrical elevation of esophagogastric junction pressure suggests hiatal repair contributes to antireflux surgery dysphagia.

The radial distribution of esophago-gastric junction (EGJ) pressures with regard to troublesome dysphagia (TDysph) after antireflux surgery is poorly understood. Before and after antireflux surgery, end-expiratory and peak-inspiratory EGJ pressures were measured at eight angles of 45° radial separation in patients with reflux disease. All 34 patients underwent posterior crural repair, then either 90° anterior (N = 13) or 360° fundoplication (N = 21). Dysphagia was assessed prospectively using a validated questionnaire (score range 0-45) and TDysph defined as a dysphagia score that was ≥5 above pre-op baseline. Compared with before surgery, for 90° fundoplication, end-expiratory EGJ pressures were highest in the left-anterolateral sectors, the position of the partial fundoplication. In other sectors, pressures were uniformly elevated. Compared with 90° fundoplication, radial pressures after 360° fundoplication were higher circumferentially (P = 0.004), with a posterior peak. Nine patients developed TDysph after surgery with a greater increase in end-expiratory and peak-inspiratory EGJ pressures (P = 0.03 and 0.03, respectively) and significantly higher inspiratory pressure at the point of maximal radial pressure asymmetry (P = 0.048), compared with 25 patients without TDysph. Circumferential elevation of end-expiratory EGJ pressure after 90° and 360° fundoplication suggests hiatal repair elevates EGJ pressure by extrinsic compression. The highly localized focal point of elevated EGJ pressure upon inspiration in patients with TDysph after surgery is indicative of a restrictive diaphragmatic hiatus in the presence of a fundoplication.

Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The survival advantage of induction chemotherapy (IC) followed by locoregional treatment is controversial in locally advanced head and neck squamous cell carcinoma (LAHNSCC). We previously showed feasibility and safety of cetuximab-based IC (paclitaxel/carboplatin/cetuximab-PCC, and docetaxel/cisplatin/5-fluorouracil/cetuximab-C-TPF) followed by local therapy in LAHNSCC. The primary end point of this phase II clinical trial with randomization to PCC and C-TPF followed by combined local therapy in patients with LAHNSCC stratified by human papillomavirus (HPV) status and T-stage was 2-year progression-free survival (PFS) compared with historical control. PATIENTS AND METHODS: Eligible patients were ≥18 years with squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx with measurable stage IV (T0-4N2b-2c/3M0) and known HPV by p16 status. Stratification was by HPV and T-stage into one of the two risk groups: (i) low-risk: HPV-positive and T0-3 or HPV-negative and T0-2; (ii) intermediate/high-risk: HPV-positive and T4 or HPV-negative and T3-4. Patient reported outcomes were carried out. RESULTS: A total of 136 patients were randomized in the study, 68 to each arm. With a median follow up of 3.2 years, the 2-year PFS in the PCC arm was 89% in the overall, 96% in the low-risk and 67% in the intermediate/high-risk groups; in the C-TPF arm 2-year PFS was 88% in the overall, 88% in the low-risk and 89% in the intermediate/high-risk groups. CONCLUSION: The observed 2-year PFS of PCC in the low-risk group and of C-TPF in the intermediate/high-risk group showed a 20% improvement compared with the historical control derived from RTOG-0129, therefore reaching the primary end point of the trial.

Weak correlation of bleeding scores to platelet electron microscopy: A retrospective chart review of pediatric patients with delta-storage pool disorder.

BACKGROUND: Delta granule storage pool deficiency (δ-SPD) is a rare platelet disorder in which a deficiency of platelet granules leads to poor aggregation, resulting in varying clinical bleeding phenotypes. Children with δ-SPD have variable laboratory results, making the proper diagnosis and evaluation controversial. OBJECTIVES: To describe the demographic and laboratory trends of this population and to assess the value of electron microscopy in diagnostic evaluation and its correlation to bleeding symptoms. METHODS: We performed a retrospective review of 109 pediatric patients diagnosed with δ-SPD. We collected demographic information and bleeding scores using a validated bleeding assessment tool. A descriptive and exploratory analysis was performed. RESULTS: The majority of patients were female, with an average age at diagnosis of 11.61 years. Females were diagnosed at a significantly older age presenting most often with menorrhagia, while males presented most commonly with epistaxis. The majority showed normal lumiaggregometry, the mean platelet electron microscopy (PEM) value was 2.37, and the mean bleeding score was 6. Bleeding assessment tool and PEM had a significantly weak correlation. CONCLUSIONS: Patients with more dense granules per platelet had higher bleeding scores than those with fewer dense granules per platelet. The current body of evidence does not favor the use of PEM in routine clinical practice, and results are difficult to interpret. In patients with severe mucocutaneous bleeding symptoms and normal platelet aggregation studies, consideration should be given to an alternative diagnosis and further evaluation is warranted.

The protocol-guided rapid evaluation of veterans experiencing new transient neurological symptoms (PREVENT) quality improvement program: rationale and methods.

BACKGROUND: Transient ischemic attack (TIA) patients are at high risk of recurrent vascular events; timely management can reduce that risk by 70%. The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurological Symptoms (PREVENT) developed, implemented, and evaluated a TIA quality improvement (QI) intervention aligned with Learning Healthcare System principles. METHODS: This stepped-wedge trial developed, implemented and evaluated a provider-facing, multi-component intervention to improve TIA care at six facilities. The unit of analysis was the medical center. The intervention was developed based on benchmarking data, staff interviews, literature, and electronic quality measures and included: performance data, clinical protocols, professional education, electronic health record tools, and QI support. The effectiveness outcome was the without-fail rate: the proportion of patients who receive all processes of care for which they are eligible among seven processes. The implementation outcomes were the number of implementation activities completed and final team organization level. The intervention effects on the without-fail rate were analyzed using generalized mixed-effects models with multilevel hierarchical random effects. Mixed methods were used to assess implementation, user satisfaction, and sustainability. DISCUSSION: PREVENT advanced three aspects of a Learning Healthcare System. Learning from Data: teams examined and interacted with their performance data to explore hypotheses, plan QI activities, and evaluate change over time. Learning from Each Other: Teams participated in monthly virtual collaborative calls. Sharing Best Practices: Teams shared tools and best practices. The approach used to design and implement PREVENT may be generalizable to other clinical conditions where time-sensitive care spans clinical settings and medical disciplines. TRIAL REGISTRATION: clinicaltrials.gov: NCT02769338 [May 11, 2016].

Metabolic syndrome and time to pregnancy: a retrospective study of nulliparous women.

OBJECTIVE: To determine: (1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility; (2) associations between individual and an increasing number of MetS components, TTP, and infertility; and (3) whether these relationships differ by body mass index (BMI < 30 kg/m2 versus BMI ≥ 30 kg/m2 ). DESIGN: Retrospective cohort study. SETTING: Multiple centres (in Australia, Ireland, New Zealand, and the UK). POPULATION: Five thousand five hundred and nineteen low-risk nulliparous pregnant women. METHODS: Data on retrospectively reported TTP (number of months to conceive) and a blood sample to assess metabolic health were collected between 14 and 16 weeks of gestation. MetS was defined according to the International Diabetes Federation criteria. Accelerated failure time models with log-normal distribution were conducted to estimate time ratios (TRs) and 95% CIs. Differences in MetS on infertility (TTP > 12 months) were compared using a generalised linear model (Poisson distribution) with robust variance estimates (relative risks, RRs; 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounding factors. MAIN OUTCOME MEASURES: Time to pregnancy and infertility. RESULTS: Of the 5519 women included, 12.4% (n = 684) had MetS. Compared with women without MetS, women with MetS had a longer TTP (adjusted TR 1.30; 95% CI 1.15-1.46), which was similar in women who were obese and in women who were not obese. Marginal estimates for median TTP in women with MetS versus without MetS was 3.1 months (3.0-3.3 months) versus 4.1 months (3.6-4.5 months), respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62; 95% CI 1.15-2.29) or not (adjusted RR 1.73; 95% CI 1.33-2.23). Reduced high-density lipoprotein cholesterol (HDL-C) and raised triglycerides (TGs) were the main individual components associated with risk for infertility. CONCLUSION: Metabolic syndrome is associated with longer TTP and infertility, independent of obesity. Additional studies, before pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose the greatest risk to delayed fertility, or whether individual components are amenable to modification. TWEETABLE ABSTRACT: Metabolic syndrome is associated with longer time to pregnancy and infertility, independent of obesity.

Placental growth factor testing for suspected pre-eclampsia: a cost-effectiveness analysis.

OBJECTIVE: To calculate the cost-effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care. DESIGN: Cost-effectiveness analysis. SETTING: Eleven maternity units participating in the PARROT stepped-wedge cluster-randomised controlled trial. POPULATION: Women presenting with suspected pre-eclampsia between 20+0 and 36+6  weeks' gestation. METHODS: Monte Carlo simulation utilising resource use data and maternal adverse outcomes. MAIN OUTCOME MEASURES: Cost per maternal adverse outcome prevented. RESULTS: Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost-saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost-saving of UK£2,891,196 each year across the NHS in England. CONCLUSIONS: Clinical care with PlGF testing is associated with the potential for cost-savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre-eclampsia. TWEETABLE ABSTRACT: Placental growth factor testing for suspected pre-eclampsia is cost-saving and improves maternal outcomes.

Longitudinal changes in vascular function parameters in pregnant women with chronic hypertension and association with adverse outcome: a cohort study.

OBJECTIVES: Raised vascular function measures are associated with adverse maternal and perinatal outcomes in low-risk pregnancy. This study aimed to evaluate the association between longitudinal vascular function parameters and adverse outcome in pregnant women with chronic hypertension, and to assess whether these measures vary according to baseline parameters such as black ethnicity. METHODS: This was a nested cohort study of women with chronic hypertension and a singleton pregnancy recruited to the PANDA (Pregnancy And chronic hypertension: NifeDipine vs lAbetalol as antihypertensive treatment) study at one of three UK maternity units. Women had serial pulse-wave analyses performed using the Arteriograph®, while in a sitting position, from 12 weeks' gestation onwards. Statistical analysis was performed using random-effects logistic regression models. Longitudinal vascular parameters were compared between women who developed superimposed pre-eclampsia (SPE) and those who did not, between women who delivered a small-for-gestational-age (SGA) infant (birth weight < 10th centile) and those who delivered an infant with birth weight ≥ 10th centile and between women of black ethnicity and those of non-black ethnicity. RESULTS: The cohort included 97 women with chronic hypertension and a singleton pregnancy, of whom 90% (n = 87) were randomized to antihypertensive treatment and 57% (n = 55) were of black ethnicity, with up to six (mean, three) longitudinal vascular function assessments. SPE was diagnosed in 18% (n = 17) of women and 30% (n = 29) of infants were SGA. In women who developed subsequent SPE, compared with those who did not, mean brachial systolic blood pressure (SBP) (148 mmHg vs 139 mmHg; P = 0.002), mean diastolic blood pressure (DBP) (87 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (139 mmHg vs 128 mmHg; P = 0.001) and mean augmentation index (AIx-75) (29% vs 22%; P = 0.01) were significantly higher across gestation. In women who delivered a SGA infant compared to those who delivered an infant with birth weight ≥ 10th centile, mean brachial SBP (146 mmHg vs 138 mmHg; P = 0.001), mean DBP (86 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (137 mmHg vs 127 mmHg; P < 0.0001) and mean pulse-wave velocity (9.1 m/s vs 8.5 m/s; P = 0.02) were higher across gestation. No longitudinal differences were found in vascular function parameters in women of black ethnicity compared with those of non-black ethnicity. CONCLUSION: There were persistent differences in vascular function parameters and brachial blood pressure throughout pregnancy in women with chronic hypertension who later developed adverse maternal or perinatal outcome. Further investigation into the possible clinical use of these findings is warranted. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.