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Extracorporeal cardiopulmonary resuscitation (ECPR) is commonly initiated for adults experiencing cardiac arrest within the cardiac catheterization lab or the intensive care unit. However, the potential benefit of ECPR for these patients in the emergency department (ED) remains undocumented. This study aims to assess the benefit of ECPR initiated in the ED for patients with out-of-hospital cardiac arrest (OHCA). We conducted a systematic review and meta-analysis of studies comparing ECPR initiated in the ED versus conventional CPR. Relevant articles were identified by searching several databases including PubMed, EMBASE, Web of Science, and Cochrane collaborations up to July 31, 2022. Pooled estimates were calculated using the inverse variance heterogeneity method, while heterogeneity was evaluated using Q and I2 statistics. The risk of bias in included studies was evaluated using validated bias assessment tools. The primary outcome was a favorable neurological outcome at hospital discharge, and the secondary outcome was survival to hospital discharge or 30-day survival. Sensitivity analyses were performed to explore the benefits of ED-initiated ECPR in studies utilizing propensity score (PPS) analysis. Publication bias was assessed using Doi plots and the Luis Furuya-Kanamori (LFK) index. The meta-analysis included a total of eight studies comprising 51,173 patients. ED-initiated ECPR may not be associated with a significant increase in favorable neurological outcomes (odds ratio [OR] 1.43, 95% confidence interval [CI] 0.30-6.70, I2 = 96%). However, this intervention may be linked to improved survival to hospital discharge (OR 3.34, 95% CI 2.23-5.01, I2 = 17%). Notably, when analyzing only PPS data, ED-initiated ECPR demonstrated efficacy for both favorable neurological outcomes (OR 1.89, 95% CI 1.26-2.83, I2 = 21%) and survival to hospital discharge (OR 3.37, 95% CI 1.52-7.49, I2 = 57%). Publication bias was detected for primary (LFK index 2.50) and secondary (LFK index 2.14) outcomes. The results of this study indicate that ED-initiated ECPR may not offer significant benefits in terms of favorable neurological outcomes for OHCA patients. However, it may be associated with increased survival to hospital discharge. Future studies should prioritize randomized trials with larger sample sizes and strive for homogeneity in patient populations to obtain more robust evidence in this area.

Large language models (LLMs) can improve text analysis efficiency in healthcare. This study explores the application of LLMs to analyze patient perspectives within the exception from informed consent (EFIC) process, which waives consent in emergency research. Our objective is to assess whether LLMs can analyze patient perspectives in EFIC interviews with performance comparable to human reviewers. We analyzed 102 EFIC community interviews from 9 sites, each with 46 questions, as part of the Pediatric Dose Optimization for Seizures in Emergency Medical Services study. We evaluated 5 LLMs, including GPT-4, to assess sentiment polarity on a 5-point scale and classify responses into predefined thematic classes. Three human reviewers conducted parallel analyses, with agreement measured by Cohen’s Kappa and classification accuracy. Polarity scores between LLM and human reviewers showed substantial agreement (Cohen’s kappa: 0.69, 95% CI 0.61–0.76), with major discrepancies in only 4.7% of responses. LLM achieved high thematic classification accuracy (0.868, 95% CI 0.853–0.881), comparable to inter-rater agreement among human reviewers (0.867, 95% CI 0.836–0.901). LLMs enabled large-scale visual analysis, comparing response statistics across sites, questions, and classes. LLMs efficiently analyzed patient perspectives in EFIC interviews, showing substantial sentiment assessment and thematic classification performance. However, occasional underperformance suggests LLMs should complement, not replace, human judgment. Future work should evaluate LLM integration in EFIC to enhance efficiency, reduce subjectivity, and support accurate patient perspective analysis.

Trauma is a major cause of morbidity and mortality in older adults and will become more common as the population ages. Tranexamic acid (TXA) is a lysine analogue frequently used in the setting of significant trauma with hemorrhage. The aim of this study is to investigate the heterogeneity of treatment effect of TXA as it relates to patient age during trauma care. We included patients from the CRASH-2 trial who were randomized within 3 h of injury. Patients were stratified into age groups <26 years, 26 to 35 years, 36 to 45 years, 46 to 55 years, and >55 years. Multiple logistic regression models were utilized to evaluate adjusted odds ratios (OR) with 95% confidence intervals (CI) for mortality. Heterogeneity of treatment effect was evaluated using Akaike and Bayesian information criteria to determine the optimum logistic regression model after which a Wald Chi-square test was utilized to evaluate statistical significance. On univariate analysis, TXA administration decreased mortality within the <26 years cohort (decrease of 2.1%, 95% CI 0.2 to 4.0), 46 to 55 years cohort (decrease 6.7%, 95% CI 2.7 to 10.7), and >55 years cohort (decrease of 5.3%, 95% CI 0.4 to 10.3). On adjusted analysis, when compared to the 36 to 45 years cohort, the <26 year cohort experienced a decreased mortality (OR 0.72, 95% CI 0.62 to 0.85) whereas the >55 year cohort experienced increased mortality (OR 1.8, 95% CI 1.5 to 2.2). Assessment for heterogeneity of treatment effect of TXA administration between groups approached but did not reach statistical significance (p = 0.11). Mortality related to trauma increases with age, however, there does not appear to be heterogeneity of treatment effect for TXA administration among different age groups.

The antifibrinolytic agent tranexamic acid (TXA) has demonstrated clinical benefit in trauma patients with severe bleeding, but its effectiveness in patients with traumatic brain injury (TBI) is unclear. We conducted a systematic review to evaluate the following research question: In ED patients with or at risk of intracranial hemorrhage (ICH) secondary to TBI, does TXA compared to placebo improve patients' outcomes? MEDLINE, EMBASE, CINAHL, and other databases were searched for randomized controlled trial (RCT) or quasi-RCT studies that compared the effect of TXA to placebo on outcomes of TBI patients. The main outcomes of interest included mortality, neurologic function, hematoma expansion, and adverse effects. We used “Grading quality of evidence and strength of recommendations” to assess the quality of trials. Two authors independently abstracted data using a data collection form. Results from studies were pooled when appropriate. Of 1030 references identified through the search, 2 high-quality RCTs met inclusion criteria. The effect of TXA on mortality had a pooled relative risk of 0.64 (95% confidence interval [CI], 0.41-1.02); on unfavorable functional status, a relative risk of 0.77 (95% CI, 0.59-1.02); and on ICH progression, a relative risk of 0.76 (95% CI, 0.58-0.98). No serious adverse effects (such as thromboembolic events) associated with TXA group were reported in the included trials. Pooled results from the 2 RCTs demonstrated statistically significant reduction in ICH progression with TXA and a nonstatistically significant improvement of clinical outcomes in ED patients with TBI. Further evidence is required to support its routine use in patients with TBI.

A pediatric field triage strategy that meets the national policy benchmark of ≥95% sensitivity would likely improve health outcomes but increase heath care costs. Our objective was to compare the cost-effectiveness of current pediatric field triage practices to an alternative field triage strategy that meets the national policy benchmark of ≥95% sensitivity. We developed a decision-analysis Markov model to compare the outcomes and costs of the two strategies. We used a prospectively collected cohort of 3507 (probability weighted, unweighted n = 2832) injured children transported by 44 emergency medical services (EMS) agencies to 28 trauma and non-trauma centers in the Northwestern United States from 1/1/2011 to 12/31/2011 to derive the alternative field triage strategy and to populate model probability and cost inputs for both strategies. We compared the two strategies by calculating quality adjusted life years (QALYs) and health care costs over a time horizon from the time of injury until death. We set an incremental cost-effectiveness ratio threshold of less than $100,000 per QALY for the alternative field triage to be a cost-effective strategy. Current pediatric field triage practices had a sensitivity of 87.4% (95% confidence interval [CI] 71.9 to 95.0%) and a specificity of 82.3% (95% CI 81.0 to 83.5%) and the alternative field triage strategy had a sensitivity of 97.3% (95% CI 82.6 to 99.6%) and a specificity of 46.1% (95% CI 43.8 to 48.4%). The alternative field triage strategy would cost $476,396 per QALY gained compared to current pediatric field triage practices and thus would not be a cost-effective strategy. Sensitivity analyses demonstrated similar findings. Current field triage practices do not meet national policy benchmarks for sensitivity. However, an alternative field triage strategy that meets the national policy benchmark of ≥95% sensitivity is not a cost-effective strategy.

Background Trauma is the leading cause of death and disability in children in the USA. Tranexamic acid (TXA) reduces the blood transfusion requirements in adults and children during surgery. Several studies have evaluated TXA in adults with hemorrhagic trauma, but no randomized controlled trials have occurred in children with trauma. We propose a Bayesian adaptive clinical trial to investigate TXA in children with brain and/or torso hemorrhagic trauma. Methods/design We designed a double-blind, Bayesian adaptive clinical trial that will enroll up to 2000 patients. We extend the traditional E max dose-response model to incorporate a hierarchical structure so multiple doses of TXA can be evaluated in different injury populations (isolated head injury, isolated torso injury, or both head and torso injury). Up to 3 doses of TXA (15 mg/kg, 30 mg/kg, and 45 mg/kg bolus doses) will be compared to placebo. Equal allocation between placebo, 15 mg/kg, and 30 mg/kg will be used for an initial period within each injury group. Depending on the dose-response curve, the 45 mg/kg arm may open in an injury group if there is a trend towards increasing efficacy based on the observed relationship using the data from the lower doses. Response-adaptive randomization allows each injury group to differ in allocation proportions of TXA so an optimal dose can be identified for each injury group. Frequent interim stopping periods are included to evaluate efficacy and futility. The statistical design is evaluated through extensive simulations to determine the operating characteristics in several plausible scenarios. This trial achieves adequate power in each injury group. Discussion This trial design evaluating TXA in pediatric hemorrhagic trauma allows for three separate injury populations to be analyzed and compared within a single study framework. Individual conclusions regarding optimal dosing of TXA can be made within each injury group. Identifying the optimal dose of TXA, if any, for various injury types in childhood may reduce death and disability.

The CRASH-2 trial demonstrated that tranexamic acid (TXA) reduced mortality with no increase in adverse events in severely injured adults. TXA has since been widely used in injured adults worldwide. Our objective was to estimate mortality and adverse events in adults with trauma receiving TXA in studies published after the CRASH-2 trial. We systematically searched PubMed, Embase, MicroMedex, and ClinicalTrials.gov for studies that included injured adults who received TXA and reported mortality and/or adverse events. Two reviewers independently assessed study eligibility, abstracted data, and assessed the risk of bias. We conducted meta-analyses using random effects models to estimate the incidence of mortality at 28 or 30 days and in-hospital thrombotic events. We included 19 studies and 13 studies in the systematic review and meta-analyses, respectively. The pooled incidence of mortality at 28 or 30 days (five studies, 1538 patients) was 10.1% (95% confidence interval [CI], 7.8-12.4%) (vs 14.5% [95% CI, 13.9-15.2%] in the CRASH-2 trial), and the pooled incidence of in-hospital thrombotic events (nine studies, 1656 patients) was 5.9% (95% CI, 3.3-8.5%) (vs 2.0% [95% CI, 1.8-2.3%] in the CRASH-2 trial). Compared to the CRASH-2 trial, adult trauma patients receiving TXA identified in our systematic review had a lower incidence of mortality at 28 or 30 days, but a higher incidence of in-hospital thrombotic events. Our findings neither support nor refute the findings of the CRASH-2 trial but suggest that incidence rates in adults with trauma in settings outside of the CRASH-2 trial may be different than those observed in the CRASH-2 trial.

The objective of this study was to conduct a systematic review and meta‐analysis of the diagnostic accuracy of the clinical signs, symptoms, laboratory investigations, and imaging modalities commonly used in patients with clinically suspected renal colic. We conducted this systematic review and meta‐analysis according to an a priori, registered protocol (PROSPERO CRD42017055153). A literature search was performed using MEDLINE and EMBASE from inception to July 2, 2020. We assessed the risk of bias using Quality Assessment of Diagnostic Accuracy Studies–2, calculated likelihood ratios (LRs), and applied a random‐effects model for meta‐analysis. Among 7641 references screened, 76 were included in the systematic review and 53 were included in the meta‐analyis. The overall pooled prevalence for ureteral stones was 63% (95% confidence interval [CI], 58%–67%). No individual demographic feature, symptom, or sign when present had an LR+ ≥2.0 for identifying ureterolithiasis. A (Sex, Timing and Origin of pain, race, presence or absence of Nausea, and Erythrocytes) STONE score ≥10 increased (sensitivity 0.49, specificity 0.91, LR 5.3 [95% CI, 4.1–6.7]) and a STONE score <6 reduced the likelihood of ureteral stones (sensitivity 0.94, specificity 0.43, LR 0.15 [95% CI, 0.10–0.22]). Standard‐dose (sensitivity 0.96, specificity 0.94, LR+ 16 [95% CI, 11–23], LR− 0.05 [95% CI, 0.03–0.07]) and low‐dose computed tomography (CT) scanning (sensitivity 0.93, specificity 0.94, LR+ 17 [95% CI, 8.8–31], LR− 0.08 [95% CI, 0.03–0.19]) were the most useful imaging techniques for identifying patients with or without ureteral stones. Individual signs, symptoms, or the presence of microscopic hematuria do not substantially impact the likelihood of ureteral stones in patients with clinically suspected renal colic. The STONE score at high and low thresholds and a modified STONE score at a high threshold may sufficiently guide physicians’ decisions to obtain imaging. Low‐dose, non‐contrast CT imaging provides superior diagnostic accuracy compared with all other imaging index tests that are comparable with standard CT imaging. Limitations of the evidence include methodological shortcomings and considerable heterogeneity of the included studies.

We evaluated the acceptability of the Pediatric Quality of Life Inventory (PedsQL) and other outcomes as the primary outcomes for a pediatric hemorrhagic trauma trial (TIC-TOC) among clinicians. We conducted a mixed-methods study that included an electronic questionnaire followed by teleconference discussions. Participants confirmed or rejected the PedsQL as the primary outcome for the TIC-TOC trial and evaluated and proposed alternative primary outcomes. Responses were compiled and a list of themes and representative quotes was generated. 73 of 91 (80%) participants completed the questionnaire. 61 (84%) participants agreed that the PedsQL is an appropriate primary outcome for children with hemorrhagic brain injuries. 32 (44%) participants agreed that the PedsQL is an acceptable primary outcome for children with hemorrhagic torso injuries, 27 (38%) participants were neutral, and 13 (18%) participants disagreed. Several themes were identified from responses, including that the PedsQL is an important and patient-centered outcome but may be affected by other factors, and that intracranial hemorrhage progression assessed by brain imaging (among patients with brain injuries) or blood product transfusion requirements (among patients with torso injuries) may be more objective outcomes than the PedsQL. The PedsQL was a well-accepted proposed primary outcome for children with hemorrhagic brain injuries. Traumatic intracranial hemorrhage progression was favored by a subset of clinicians. A plurality of participants also considered the PedsQL an acceptable outcome for children with hemorrhagic torso injuries. Blood product transfusion requirement was favored by fewer participants. •Across a multidisciplinary cohort of clinicians, the PedsQL was a well-accepted outcome in a trial of injured children•Intracranial hemorrhage progression and blood transfusion requirement was favored by a smaller subset of clinicians•The main concern about the PedsQL as an outcome was it may be impacted by other factors outside of the study intervention

Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry. Body and bone weight of both age groups decreased and became significantly lower than those of wild-type mice. The bones of SMP30/GNL KO mice were rough and porous, with BMC and BMD significantly below wild-type. Oral supplementation with vitamin C eliminated differences in body weight, bone weight, BMC, and BMD between SMP30/GNL KO and wild-type mice at each age. These results indicate that bone degeneration in SMP30/GNL KO mice was caused by lack of vitamin C, and that this mouse strain is an appropriate model for bone metabolism in humans, which have no ability to synthesize vitamin C.