Prospective observational study of peripheral intravenous cannula utilisation and frequency of intravenous fluid delivery in the emergency department-Convenience or necessity?

BACKGROUND: Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with complications and have an associated cost to departmental resources. A growing body of international research suggests many of the PIVCs inserted in the ED are unnecessary. METHODS: The objective of this study was to determine the rates of PIVC insertion and use. This was a prospective observational study conducted in one UK ED and one Italian ED. Adult ED patients with non-immediate triage categories were included over a period of three weeks in the UK ED in August 2016 and two weeks in the Italian ED in March and August 2017. Episodes of PIVC insertion and data on PIVC utilisation in adults were recorded. PIVC use was classified as necessary, unnecessary or unused. The proportion of unnecessary and unused PIVCs was calculated. PIVCs were defined as unnecessary if they were either used for phlebotomy only, or solely for IV fluids in patients that could have potentially been hydrated orally (determined against a priori defined criteria). PIVC classified as unused were not used for any purpose. RESULTS: A total of 1,618 patients were included amongst which 977 PIVCs were inserted. Of the 977 PIVCs, 413 (42%) were necessary, 536 (55%) were unnecessary, and 28 (3%) were unused. Of the unnecessary PIVCs, 473 (48%) were used solely for phlebotomy and 63 (6%) were used for IV fluids in patients that could drink. CONCLUSIONS: More than half of PIVCs placed in the ED were unnecessary in this study. This suggests that clinical decision making about the benefits and risks of PIVC insertion is not being performed on an individual basis.

A randomised clinical trial of awake prone positioning in COVID-19 suspects with acute hypoxemic respiratory failure.

Background: Awake prone position (APP) has been reported to improve oxygenation in patients with COVID-19 disease and to reduce the requirement for invasive mechanical ventilation for patients requiring support with high flow nasal cannula. There is conflicting data for patients requiring lower-level oxygen support. Research question: Does APP reduce escalation of oxygen support in COVID-19 patients requiring supplementary oxygen?The primary outcome was defined as an escalation of oxygen support from simple supplementary oxygen (NP, HM, NRB) to NIV (CPAP or BiPAP), HFNC or IMV; OR from NIV (CPAP or BiPAP) or HFNC to IMV by day30. Study design: Two center, prospective, non-blind, randomised controlled trial. Patients with confirmed or suspected COVID-19 pneumonia requiring ≥ 5 liters/min oxygen to maintain saturations ≥ 94 % were randomised to either APP or control group. The APP group received a 3-h APP session three times per day for three days. Results: Between 9 May and July 13, 2021, 89 adults were screened and 61 enrolled, 31 to awake prone position and 30 controls. There was no difference in the primary outcome, 7 (22.6 %) patients randomised to APP and 9 (30.0 %) controls required escalation of oxygen support (OR 0.68 (0.22-2.14), P = 0.51). There were no differences in any secondary outcomes, in APP did not improve oxygenation. Interpretation: In COVID-19 patients, the use of APP did not prevent escalation of oxygen support from supplementary to invasive or non-invasive ventilation or improve patient respiratory physiology. Trial registration: NCT04853979 (clinicaltrials.gov).

The incidence of admission ionised hypocalcaemia in paediatric major trauma-A systematic review and meta-analysis.

OBJECTIVES: In adult major trauma patients admission hypocalcaemia occurs in approximately half of cases and is associated with increased mortality. However, data amongst paediatric patients are limited. The objectives of this review were to determine the incidence of admission ionised hypocalcaemia in paediatric major trauma patients and to explore whether hypocalcaemia is associated with adverse outcomes. METHODS: A systematic review was conducted following PRISMA guidelines. All studies including major trauma patients <18 years old, with an ionised calcium concentration obtained in the Emergency Department (ED) prior to the receipt of blood products in the ED were included. The primary outcome was incidence of ionised hypocalcaemia. Random-effects Sidik-Jonkman modelling was executed for meta-analysis of mortality and pH difference between hypo- and normocalcaemia, Odds ratio (OR) was the reporting metric for mortality. The reporting metric for the continuous variable of pH difference was Glass' D (a standardized difference). Results are reported with 95% confidence intervals (CIs) and significance was defined as p <0.05. RESULTS: Three retrospective cohort studies were included. Admission ionised hypocalcaemia definitions ranged from <1.00 mmol/l to <1.16 mmol/l with an overall incidence of 112/710 (15.8%). For mortality, modelling with low heterogeneity (I2 39%, Cochrane's Q p = 0.294) identified a non-significant (p = 0.122) estimate of hypocalcaemia increasing mortality (pooled OR 2.26, 95% CI 0.80-6.39). For the pH difference, meta-analysis supported generation of a pooled effect estimate (I2 57%, Cochrane's Q p = 0.100). The effect estimate of the mean pH difference was not significantly different from null (p = 0.657), with the estimated pH slightly lower in hypocalcaemia (Glass D standardized mean difference -0.08, 95% CI -0.43 to 0.27). CONCLUSION: Admission ionised hypocalcaemia was present in at least one in six paediatric major trauma patients. Ionised hypocalcaemia was not identified to have a statistically significant association with mortality or pH difference.

Epidemiological profile of stroke in Qatar: Insights from a seven-year observational study.

OBJECTIVES: Stroke prevalence is progressively increasing in developing countries due to increased vascular risk factors. This study aims to describe the epidemiology, prevalent risk factors, and outcomes of stroke in a multi-ethnic society of Qatar. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients with suspected stroke admitted to stroke services between January 2014 and September 2020. RESULTS: A total of 11,892 patients were admitted during this period with suspected stroke. Of these, the diagnosis was ischemic stroke (48.8 %), transient ischemic attack (10.3 %), intracerebral hemorrhage (10.9 %), cerebral venous sinus thrombosis (1.3 %), and stroke mimics (28.6 %). The median age was 52 (43-62), with a male-female ratio of 3:1. The study population was predominantly Asian (56.8 %) and Arab (36 %). The majority of the patients were hypertensive (66.8 %), diabetic (47.9 %), and dyslipidemic (45.9 %). A history of prior stroke was observed in 11.7 %, while 0.9 % had prior transient ischemic attack. Among ischemic strokes, 31.7 % arrived within 4.5 h, 12.5 % received thrombolysis, and 4.6 % underwent thrombectomy. Median Door-to-Needle time was 51 (33-72) minutes. The average length of stay was 5.2 ± 9.0 days, with 71.5 % discharged home, 13.8 % transferred to rehabilitation, 9.3 % to other specialties, 3 % to long-term care, and 2.4 % suffered in-hospital mortality. CONCLUSION: Stroke in Qatar is characterized by a younger, expatriate-dominant cohort, with notable prevalence of ischemic and hemorrhagic stroke and a distinct risk factor profile. Further analysis of epidemiological differences among different population groups can inform targeted policies for prevention and management to reduce the burden of disease.

Assessing the one-month mortality impact of civilian-setting prehospital transfusion: A systematic review and meta-analysis.

BACKGROUND: Based on convincing evidence for outcomes improvement in the military setting, the past decade has seen evaluation of prehospital transfusion (PHT) in the civilian emergency medical services (EMS) setting. Evidence synthesis has been challenging, due to study design variation with respect to both exposure (type of blood product administered) and outcome (endpoint definitions and timing). The goal of the current meta-analysis was to execute an overarching assessment of all civilian-arena randomized controlled trial (RCT) evidence focusing on administration of blood products compared to control of no blood products. METHOD: The review structure followed the Cochrane group's Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Using the Transfusion Evidence Library (transfusionevidencelibrary.com), the multidatabase (e.g. PubMed, EMBASE) Harvard On-Line Library Information System (HOLLIS), and GoogleScholar, we accessed many databases and gray literature sources. RCTs of PHT in the civilian setting with a comparison group receiving no blood products with 1-month mortality outcomes were identified. RESULTS: In assessing a single patient-centered endpoint-1-month mortality-we calculated an overall risk ratio (RR) estimate. Analysis of three RCTs yielded a model with acceptable heterogeneity (I2 = 48%, Q-test p = 0.13). Pooled estimate revealed civilian PHT results in a statistically nonsignificant (p = 0.38) relative mortality reduction of 13% (RR 0.87, 95% CI 0.63-1.19). CONCLUSIONS: Current evidence does not demonstrate 1-month mortality benefit of civilian-setting PHT. This should give pause to EMS systems considering adoption of civilian-setting PHT programs. Further studies should not only focus on which formulations of blood products might improve outcomes but also focus on which patients are most likely to benefit from any form of civilian-setting PHT.

Can absence of cardiac activity on point-of-care echocardiography predict death in out-of-hospital cardiac arrest? A systematic review and meta-analysis.

AIM: The purpose of this systematic review and meta-analysis was to evaluate the accuracy of the absence of cardiac motion on point-of-care echocardiography (PCE) in predicting termination of resuscitation (TOR), short-term death (STD), and long-term death (LTD), in adult patients with cardiac arrest of all etiologies in out-of-hospital and emergency department setting. METHODS: A systematic review and meta-analysis was conducted based on PRISMA guidelines. A literature search in Medline, EMBASE, Cochrane, WHO registry, and ClinicalTrials.gov was performed from inspection to August 2022. Risk of bias was evaluated using QUADAS-2 tool. Meta-analysis was divided into medical cardiac arrest (MCA) and traumatic cardiac arrest (TCA). Sensitivity and specificity were calculated using bivariate random-effects, and heterogeneity was analyzed using I2 statistic. RESULTS: A total of 27 studies (3657 patients) were included in systematic review. There was a substantial variation in methodologies across the studies, with notable difference in inclusion criteria, PCE timing, and cardiac activity definition. In MCA (15 studies, 2239 patients), the absence of cardiac activity on PCE had a sensitivity of 72% [95% CI 62-80%] and specificity of 80% [95% CI 58-92%] to predict LTD. Although the low numbers of studies in TCA preluded meta-analysis, all patients who lacked cardiac activity on PCE eventually died. CONCLUSIONS: The absence of cardiac motion on PCE for MCA predicts higher likelihood of death but does not have sufficient accuracy to be used as a stand-alone tool to terminate resuscitation. In TCA, the absence of cardiac activity is associated with 100% mortality rate, but low number of patients requires further studies to validate this finding. Future work would benefit from a standardized protocol for PCE timing and agreement on cardiac activity definition.

Prognostic accuracy of qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients presenting with suspected infection to the emergency department (PASSEM) Multicenter prospective external validation cohort study protocol.

BACKGROUND: Early identification of a patient with infection who may develop sepsis is of utmost importance. Unfortunately, this remains elusive because no single clinical measure or test can reflect complex pathophysiological changes in patients with sepsis. However, multiple clinical and laboratory parameters indicate impending sepsis and organ dysfunction. Screening tools using these parameters can help identify the condition, such as SIRS, quick SOFA (qSOFA), National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS). We aim to externally validate qSOFA, SIRS, and NEWS/NEWS2/MEWS for in-hospital mortality among adult patients with suspected infection who presenting to the emergency department. METHODS AND ANALYSIS: PASSEM study is an international prospective external validation cohort study. For 9 months, each participating center will recruit consecutive adult patients who visited the emergency departments with suspected infection and are planned for hospitalization. We will collect patients' demographics, vital signs measured in the triage, initial white blood cell count, and variables required to calculate Charlson Comorbidities Index; and follow patients for 90 days since their inclusion in the study. The primary outcome will be 30-days in-hospital mortality. The secondary outcome will be intensive care unit (ICU) admission, prolonged stay in the ICU (i.e., ≥72 hours), and 30- as well as 90-days all-cause mortality. The study started in December 2021 and planned to enroll 2851 patients to reach 200 in-hospital death. The sample size is adaptive and will be adjusted based on prespecified consecutive interim analyses. DISCUSSION: PASSEM study will be the first international multicenter prospective cohort study that designated to externally validate qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients with suspected infection presenting to the ED in the Middle East region. STUDY REGISTRATION: The study is registered at ClinicalTrials.gov (NCT05172479).

Incidence of admission ionised hypocalcaemia in paediatric major trauma: protocol for a systematic review and meta-analysis.

INTRODUCTION: Hypocalcaemia forms part of the 'diamond of death' in major trauma, alongside hypothermia, acidosis and coagulopathy. In adults, admission hypocalcaemia prior to transfusion is associated with increased mortality, increased blood transfusion requirements and coagulopathy. Data on paediatric major trauma patients are limited. This systematic review and meta-analysis aims to describe and synthesise the available evidence relevant to paediatric trauma, admission hypocalcaemia and outcome. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines will be used to construct this review. A planned literature search for articles in the English language will be conducted from inception to the date of searches using MEDLINE on the EBSCO platform, CINAHL on the EBSCO platform and Embase on the Ovid platform. The grey literature will also be searched. Both title and abstract screening and full-text screening will be done by two reviewers, with an adjudicating third reviewer. Heterogeneity will be assessed using the I2 test, and the risk of bias will be assessed using the ROBINS-I tool. A meta-analysis will be undertaken using ratio measures (OR) and mean differences for measures of effect. When possible, the estimate of effect will be presented along with a CI and a p value. ETHICAL REVIEW AND DISSEMINATION: Ethical review is not required, as no original data will be collected. Results will be disseminated through peer-reviewed publications and at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023425172.

Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial.

Importance: Bleeding is the most common cause of preventable death after trauma. Objective: To determine the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) when used in the emergency department along with standard care vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage. Design, Setting, and Participants: Pragmatic, bayesian, randomized clinical trial conducted at 16 major trauma centers in the UK. Patients aged 16 years or older with exsanguinating hemorrhage were enrolled between October 2017 and March 2022 and followed up for 90 days. Intervention: Patients were randomly assigned (1:1 allocation) to a strategy that included REBOA and standard care (n = 46) or standard care alone (n = 44). Main Outcomes and Measures: The primary outcome was all-cause mortality at 90 days. Ten secondary outcomes included mortality at 6 months, while in the hospital, and within 24 hours, 6 hours, or 3 hours; the need for definitive hemorrhage control procedures; time to commencement of definitive hemorrhage control procedures; complications; length of stay; blood product use; and cause of death. Results: Of the 90 patients (median age, 41 years [IQR, 31-59 years]; 62 [69%] were male; and the median Injury Severity Score was 41 [IQR, 29-50]) randomized, 89 were included in the primary outcome analysis because 1 patient in the standard care alone group declined to provide consent for continued participation and data collection 4 days after enrollment. At 90 days, 25 of 46 patients (54%) had experienced all-cause mortality in the REBOA and standard care group vs 18 of 43 patients (42%) in the standard care alone group (odds ratio [OR], 1.58 [95% credible interval, 0.72-3.52]; posterior probability of an OR >1 [indicating increased odds of death with REBOA], 86.9%). Among the 10 secondary outcomes, the ORs for mortality and the posterior probabilities of an OR greater than 1 for 6-month, in-hospital, and 24-, 6-, or 3-hour mortality were all increased in the REBOA and standard care group, and the ORs were increased with earlier mortality end points. There were more deaths due to bleeding in the REBOA and standard care group (8 of 25 patients [32%]) than in standard care alone group (3 of 18 patients [17%]), and most occurred within 24 hours. Conclusions and Relevance: In trauma patients with exsanguinating hemorrhage, a strategy of REBOA and standard care in the emergency department does not reduce, and may increase, mortality compared with standard care alone. Trial Registration: isrctn.org Identifier: ISRCTN16184981.

What adult patients prefer for reporting their pain levels, and frequency of reassessment when in the emergency department.

OBJECTIVES: This study interviewed adult patients presenting to the emergency department (ED) for various pain conditions enquiring about their preferred tool for reporting pain severity and preferred time interval between initial assessment and subsequent pain reassessments. METHODS: A prospective observational (cross-sectional) study was conducted in adult patients with acute pain in a tertiary care hospital ED setting. Patients' initial pain score was recorded using NRS (numerical rating scale) pain scale, and appropriate analgesia offered. Once the patient had been evaluated by an attending physician, a research team member interviewed the patient regarding the pain reassessment time and preferred pain assessment tool. The pain assessment tools evaluated in this study were NRS, PS (picture scale or face pain scale), VRS (verbal rating scale), and VAS (visual analogue scale). The patients were presented with the four pain assessment tools (in their primary language) through an audio-visual on an electronic tablet display. RESULTS: 200 (138 male, mean age 36.5 ± 11.17) patients participated in the study. With increasing age, pain reassessment interval increased by 0.19 min (95% CI 0.03-0.36 min). Males requested pain reassessment 6.7 min (95% CI 2.2-10.8) faster than females. In this study, the preferred interval for pain reassessment was reported as a mean of 22.8 (SD + -13.6) minutes. There was no relationship reported between time reassessment and pain severity (P = 0.22). Out of 200 subjects, irrespective of the initial pain scores, 100 preferred NRS. NRS was preferred by patients with mild to moderated pain due to the perception of being faster. However, patients with severe pain choose a non-NRS scale to prioritize accuracy. CONCLUSION: There was no influence found between the initial pain severity scores and the desired frequency of pain reassessment. However, associations were identified between the time for pain reassessment interval and age, sex, and geographical region. Patients with severe pain preferred PS or VRS while patients with mild/moderate pain preferred the NRS.

Building a collaborative cloud platform to accelerate heart, lung, blood, and sleep research.

Research increasingly relies on interrogating large-scale data resources. The NIH National Heart, Lung, and Blood Institute developed the NHLBI BioData CatalystⓇ (BDC), a community-driven ecosystem where researchers, including bench and clinical scientists, statisticians, and algorithm developers, find, access, share, store, and compute on large-scale datasets. This ecosystem provides secure, cloud-based workspaces, user authentication and authorization, search, tools and workflows, applications, and new innovative features to address community needs, including exploratory data analysis, genomic and imaging tools, tools for reproducibility, and improved interoperability with other NIH data science platforms. BDC offers straightforward access to large-scale datasets and computational resources that support precision medicine for heart, lung, blood, and sleep conditions, leveraging separately developed and managed platforms to maximize flexibility based on researcher needs, expertise, and backgrounds. Through the NHLBI BioData Catalyst Fellows Program, BDC facilitates scientific discoveries and technological advances. BDC also facilitated accelerated research on the coronavirus disease-2019 (COVID-19) pandemic.

Comparison of intravenous paracetamol (acetaminophen) to intravenously or intramuscularly administered non-steroidal anti-inflammatory drugs (NSAIDs) or opioids for patients presenting with moderate to severe acute pain conditions to the ED: systematic review and meta-analysis.

OBJECTIVE: Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opiates/opioids, administered parenterally via intravenous or intramuscular route, are widely used to provide analgesia for patients with moderate to severe pain. This systematic review and meta-analysis evaluated the level of analgesia provided by intravenous paracetamol (IVP) alone compared with NSAIDs (intravenous or intramuscular), or opioids (intravenous) alone in adults attending the ED with acute pain. METHODS: Two authors independently searched PubMed (MEDLINE), Web of Science, Embase (OVID), Cochrane Library, SCOPUS and Google Scholar (3 March 2021-20 May 2022) for randomised trials without any language or date restriction. Clinical trials were evaluated using the Risk of Bias V.2 tool. The primary outcome was mean difference (MD) for pain reduction at 30 min (T30) post analgesia delivery. The secondary outcomes were MD in pain reduction at 60, 90 and 120 min; the need for rescue analgesia; and the occurrence of adverse events (AEs). RESULTS: Twenty-seven trials (5427 patients) were included in the systematic review and 25 trials (5006 patients) in the meta-analysis. There was no significant difference in pain reduction at T30 between the IVP group and opioids (MD -0.13, 95% CI -1.49 to 1.22) or IVP and NSAIDs (MD -0.27, 95% CI -1.0 to 1.54. There was also no difference at 60 min, IVP group versus opioid group (MD -0.09, 95% CI -2.69 to 2.52) or IVP versus NSAIDs (MD 0.51, 95% CI 0.11 to 0.91). The quality of the evidence using Grading of Recommendations, Assessments, Development and Evaluations methodology was low for MD in pain scores.The need for rescue analgesia at T30 was significantly higher in the IVP group compared with the NSAID group (risk ratio (RR): 1.50, 95% CI 1.23 to 1.83), with no difference found between the IVP group and the opioid group (RR: 1.07, 95% CI 0.67 to 1.70). AEs were 50% lower in the IVP group compared with the opioid group (RR: 0.50, 95% CI 0.40 to 0.62), whereas no difference was observed in the IVP group compared with the NSAID group (RR: 1.30, 95% CI 0.78 to 2.15). CONCLUSION: In patients presenting to the ED with a diverse range of pain conditions, IVP provides similar levels of pain relief compared with opiates/opioids or NSAIDs at T30 post administration. Patients treated with NSAIDs had lower risk of rescue analgesia, and opioids cause more AEs, suggesting NSAIDs as the first-choice analgesia and IVP as a suitable alternative. PROSPERO REGISTRATION NUMBER: CRD42021240099.

Comparison of cardiac index measurements in intensive care patients using continuous wave vs. pulsed wave echo-Doppler compared to pulse contour cardiac output.

PURPOSE: Cardiac index (CI) assessments are commonly used in critical care to define shock aetiology and guide resuscitation. Echocardiographic assessment is non-invasive and has high levels of agreement with thermodilution assessment of CI. CI assessment is derived from the velocity time integral (VTI) assessed using pulsed wave (PW) doppler at the level of the left ventricular outflow tract divided by body mass index. Continuous wave (CW) doppler through the aortic valve offers an alternative means to assess VTI and may offer better assessment at high velocities. METHODS: We performed a single centre, prospective, observational study in a 15-bed intensive care unit in a busy district general hospital. Patients had simultaneous measurements of cardiac index by Pulse Contour Cardiac Output (PiCCO) (thermodilution), transthoracic echocardiographic PW-VTI and CW-VTI. Mean differences were measured with Bland-Altman limits of agreement and percentage error (PE) calculations. RESULTS: Data were collected on 52 patients. 71% were supported with noradrenaline with or without additional inotropic or vasopressor agents. Mean CIs were: CW-VTI 2.7 L/min/m2 (range 0.78-5.11, SD 0.92). PW-VTI 2.33 L/min/m2 (range 0.77-5.40, SD 0.90) and PiCCO 2.86 L/min/m2 (range 1.50-5.56, SD 0.93). CW-VTI and PiCCO mean difference was - 0.16 L/min/m2 PE 43.5%. PW-VTI and PiCCO had a mean difference of - 0.54 L/min/m2 PE 38.6%. CW-VTI and PW-VTI had a mean difference of 0.38 L/min/m2 PE 46.0%. CONCLUSIONS: CI derived from both CW-VTI and PW-VTI methods underestimate CI compared to PiCCO, with the CW-VTI method having closer values overall to PiCCO. CW-VTI may offer a more accurate assessment of CI. If using Critchley's PE cutoff of 30%, none of the doppler methods may accurately reflect the actual cardiac index.

EFSUMB Clinical Practice Guidelines for Point-of-Care Ultrasound: Part One (Common Heart and Pulmonary Applications) SHORT VERSION.

OBJECTIVE: To evaluate the evidence and produce a summary and recommendations for the most common heart and lung point-of-care ultrasound (PoCUS). METHODS: We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendations were produced, including assigning levels of evidence (LoE) and grading of recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement of the summary and recommendation for each question (using a 5-point Likert scale), which was approved in the case of a level of agreement of greater than 75 %. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses. FINDINGS AND RECOMMENDATIONS: One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1), the remaining 9 questions achieved broad agreement with an assigned LoE of 4 and a weak GRADE recommendation (question 2), three achieved an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8) and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). CONCLUSION: These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings.

EFSUMB Clinical Practice Guidelines for Point-of-Care Ultrasound: Part One (Common Heart and Pulmonary Applications) LONG VERSION.

AIMS: To evaluate the evidence and produce a summary and recommendations for the most common heart and lung applications of point-of-care ultrasound (PoCUS). METHODS: We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendation were produced, including assignment of levels of evidence (LoE) and grading of the recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement regarding the summary and recommendation for each question (using a 5-point Likert scale), which was approved if a level of agreement of greater than 75 % was reached. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses. FINDINGS AND RECOMMENDATIONS: One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1). The remaining 9 questions achieved broad agreement with one assigned an LoE of 4 and weak GRADE recommendation (question 2), three achieving an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8), and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). CONCLUSION: These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings.

Plectus of the Prairie: A Case Study of Taxonomic Resolution from a Nematode Biodiversity Survey.

Taxonomic resolution is a critical component of biodiversity assessments. In this case study, we examined a single taxon within a larger study of nematode diversity to evaluate the taxonomic resolution of different diversity assessment methods. The selected taxon was the microbial-feeding genus Plectus, a group considered to include multiple cosmopolitan species. The methods included a morphological evaluation by light microscopy, Sanger sequencing of PCR amplicons of COI and 18S gene regions, and 18S metabarcoding sequencing. The study sites were 15 remnant tallgrass prairie plots in eastern Nebraska. In the morphological analysis, we observed two basic morphotypes, a short-tailed form with a small amphid and a long-tailed form with a large amphid. Sanger sequencing of COI sorted Plectus diversity into six distinct clades. The largest two of these six clades keyed to P. parietinus and P. rhizophilus based on morphology. BLAST analysis with COI revealed no close matches in GenBank. Sanger sequencing of the 18S region did not differentiate the six clades. These results illustrate that the method of diversity assessment strongly influences estimates of biodiversity. An additional 95 Plectus specimens, from outside the remnant sites, added taxonomic breadth to the COI phylogenetic tree. There were no geographically widespread COI haplotypes and no evidence of cosmopolitan Plectus species.

Genome-Wide Association Study and Gene-Based Analysis of Participants With Hemophilia A and Inhibitors in the My Life, Our Future Research Repository.

Introduction: Up to 30% of individuals with hemophilia A develop inhibitors to replacement factor VIII (FVIII), rendering the treatment ineffective. The underlying mechanism of inhibitor development remains poorly understood. The My Life, Our Future Research Repository (MLOF RR) has gathered F8 and F9 mutational information, phenotypic data, and biological material from over 11,000 participants with hemophilia A (HA) and B as well as carriers enrolled across US hemophilia treatment centers, including over 5,000 whole-genome sequences. Identifying genes associated with inhibitors may contribute to our understanding of why certain patients develop those neutralizing antibodies. Aim and Methods: Here, we performed a genome-wide association study and gene-based analyses to identify genes associated with inhibitors in participants with HA from the MLOF RR. Results: We identify a genome-wide significant association within the human leukocyte antigen (HLA) locus in participants with HA with F8 intronic inversions. HLA typing revealed independent associations with the HLA alleles major histocompatibility complex, class II, DR beta 1 (HLA DRB1*15:01) and major histocompatibility complex, class II, DQ beta 1 (DQB1*03:03). Variant aggregation tests further identified low-frequency variants within GRID2IP (glutamate receptor, ionotropic, delta 2 [GRID2] interacting protein 1) significantly associated with inhibitors. Conclusion: Overall, our study confirms the association of DRB1*15:01 with FVIII inhibitors and identifies a novel association of DQB1*03:03 in individuals with HA carrying intronic inversions of F8. In addition, our results implicate GRID2IP, encoding GRID2-interacting protein, with the development of inhibitors, and suggest an unrecognized role of this gene in autoimmunity.