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Background: Established structured weaning approaches, which are effective for patients in simple and difficult weaning, are often not appropriate for patients undergoing prolonged weaning. Addressing the complexity of weaning failure requires personalized precision medicine. The therapeutic concept of treatable traits (TTs) has been proposed as a new paradigm for the management of chronic respiratory diseases. It is based on a multidimensional assessment of specific characteristics, which can be addressed by specific interventions that go beyond traditional diagnostic criteria. The concept is increasingly adopted for other complex diseases., Summary: This is a narrative review and an expert opinion on the development of a concept of TTs for patients undergoing prolonged weaning. The proposed TTs are based on a systematic review of risk factors for prolonged weaning, an analysis of claims data to assess risk factors within 96 h of IMV onset and data from the WEAN SAFE study. A multidisciplinary team identified clinically important TTs and determined appropriate interventions. The following TTs have been identified: airway disorders and complications associated with tracheostomy or intubation, such as airway obstruction, strictures or tracheomalacia, infectious aspects, anxiety, depression, delirium, post-traumatic stress disorder, anemia, pulmonary and cardio-renal disease. The multidimensional holistic approach also includes tailored sedation and pain management, nutritional therapy, early mobilization, and physiotherapy., Key Message: We propose a framework of relevant considerations for a multidimensional approach to the management of patients undergoing prolonged weaning that supports the regain of respiratory capacity, reduces the respiratory load, and thus could resolve the respiratory workload imbalance., (© 2024 S. Karger AG, Basel.)

Background: In hypoxemic children with difficult airway, or for minor elective procedures, the use of a supraglottic airway device may be preferred to endotracheal intubation, whether with a laryngeal mask or laryngeal tube. Second-generation laryngeal masks may offer a better safety profile. Whether they should be preferred to laryngeal tubes is unknown. This study aimed to compare the efficacy and safety of second-generation laryngeal masks and laryngeal tubes in children., Methods: This randomised-controlled trial was conducted in a single university hospital in children <18 years undergoing elective anaesthesia in urology, minor paediatric surgery and gynaecology. Patients were 1 : 1 randomised to the laryngeal mask or laryngeal tube group. Children were allocated a second-generation laryngeal tube or a second-generation laryngeal mask as the primary airway device. The primary endpoint was insertion time. Secondary endpoints included first-attempt success, overall success and complications, which included hypoxia (SpO2 < 90%), laryngospasm, bronchospasm, aspiration and bleeding., Results: In total, 135 patients were randomised, with 61 allocated to the laryngeal tube and 74 to the laryngeal mask group, with a median age of 5.4 and 4.9 years, respectively. Median insertion time was significantly longer in the laryngeal tube group (37 vs. 31 s; difference of medians: 6.0 s; 95% confidence interval: 0.0-13.0). The laryngeal tube had a significantly lower first-attempt (41.0%) and overall success rate (45.9%) than the laryngeal mask (90.5% and 97.3%, respectively). Those allocated to the laryngeal tube group had a higher ratio of complications (27.8%) compared to the laryngeal mask group (2.7%)., Conclusion: This randomised-controlled trial reported that in children undergoing elective anaesthesia, the use of a laryngeal tube was associated with a longer insertion time., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: Children constitute an important and distinct subgroup of out-of-hospital cardiac arrest (OHCA) patients. This population-based cohort study aims to establish current age-specific population incidence, precipitating causes, circumstances, and outcome of paediatric OHCA, to guide a focused approach to prevention and intervention to improve outcomes., Methods: Data from the national Norwegian Cardiac Arrest Registry was extracted for the six-year period 2016-21 for persons aged <18 years. We present descriptive statistics for the population, resuscitation events, presumed causes, treatment, and outcomes, alongside age-specific incidence and total paediatric mortality rates., Results: Three hundred and eight children were included. The incidence of OHCA was 4.6 per 100 000 child-years and markedly higher in children <1 year at 20.9 child-years. Leading causes were choking, cardiac and respiratory disease, and sudden infant death syndrome. Overall, 21% survived to 30 days and 18% to one year., Conclusion: A registry-based approach enabled this study to delineate the characteristics and trajectories of OHCA events in a national cohort of children. Precipitating causes of paediatric OHCA are diverse compared to adults. Infants aged <1 year are at particularly high risk. Mortality is high, albeit lower than for adults in Norway. A rational community approach to prevention and treatment may focus on general infant care, immediate first aid by caretakers, and identification of vulnerable children by primary health providers. Cardiac arrest registries are a key source of knowledge essential for quality improvement and research into cardiac arrest in childhood., Competing Interests: The authors declared the following financial interests/personal relationships which may be considered as potential competing interests. IBMT received an unrestricted grant from the Laerdal foundation for an unrelated research project. JKJ has no conflict of interest for the current research work, but has received an unrestricted grant from the Laerdal foundation for an unrelated research project. All other authors have no conflicts of interest., (© 2024 The Authors.)

Introduction and Aim: Severe external hemorrhage is a significant reason for morbidity and mortality in adults; thus, the swift and correct application of a tourniquet by laypersons can be lifesaving. We conducted this randomized-controlled cross-over study to investigate the use of a novel tourniquet., Methods: Participants were recruited at the Heidelberg University Hospital. Eligible participants were ≥ 18 years old with a medical background but without prior experience in applying a tourniquet. Participants were 1:1 randomized to the intervention group (PAX tourniquet) or the control group (SAM or CAT tourniquet). In the control group, participants underwent another randomization to either the SAM or CAT tourniquet without a predefined allocation ratio. Hyperspectral measurements were undertaken (i) before ligation, (ii) 30 s after ligation, and (iii) 30 s after the reopening of the tourniquet. The primary outcome was time until ligation before crossover between the respective groups. The analysis of secondary endpoints included all attempts to assess a possible learning effect, intraoperator variability, and hyperspectral measurements. Participants were crossed to the other study group after a brief wash-out phase., Results: In total, 50 participants were recruited, resulting in 100 attempts. A success rate of 98% was observed across the study population. Time until ligation was 49 s and 56 s (p = 0.572) in the intervention and control group, respectively. However, there was a significant difference between the PAX and SAM (54 vs 75 s; p = 0.037) and the SAM and CAT tourniquet (75 vs. 47 s; p = 0.015). Further, we observed a significant learning effect in participants allocated to the control group first, with a median reduction of 9 s in the time until ligation. Hyperspectral measurements showed a significant decrease in perfusion and tissue oxygenation after ligation. Further, a significant increase in perfusion and tissue oxygenation was found after reopening the tourniquet compared to the baseline measurement., Conclusion: The novel PAX tourniquet can be applied quickly and effectively by medical personnel without prior experience in applying a tourniquet., Competing Interests: Declaration of competing interest All authors have made substantial contributions to the following: (1) the conception and design of the study, acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it critically for important intellectual content; and (3) final approval of the version to be submitted., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: During the COVID-19 pandemic, antigen diagnostic tests were frequently used for screening, triage, and diagnosis. Novel instrument-based antigen tests (iAg tests) hold the promise of outperforming their instrument-free, visually-read counterparts. Here, we provide a systematic review and meta-analysis of the SARS-CoV-2 iAg tests' clinical accuracy., Methods: We systematically searched MEDLINE (via PubMed), Web of Science, medRxiv, and bioRxiv for articles published before November 7th, 2022, evaluating the accuracy of iAg tests for SARS-CoV-2 detection. We performed a random effects meta-analysis to estimate sensitivity and specificity and used the QUADAS-2 tool to assess study quality and risk of bias. Sub-group analysis was conducted based on Ct value range, IFU-conformity, age, symptom presence and duration, and the variant of concern., Results: We screened the titles and abstracts of 20,431 articles and included 114 publications that fulfilled the inclusion criteria. Additionally, we incorporated three articles sourced from the FIND website, totaling 117 studies encompassing 95,181 individuals, which evaluated the clinical accuracy of 24 commercial COVID-19 iAg tests. The studies varied in risk of bias but showed high applicability. Of 24 iAg tests from 99 studies assessed in the meta-analysis, the pooled sensitivity and specificity compared to molecular testing of a paired NP swab sample were 76.7% (95% CI 73.5 to 79.7) and 98.4% (95% CI 98.0 to 98.7), respectively. Higher sensitivity was noted in individuals with high viral load (99.6% [95% CI 96.8 to 100] at Ct-level ≤ 20) and within the first week of symptom onset (84.6% [95% CI 78.2 to 89.3]), but did not differ between tests conducted as per manufacturer's instructions and those conducted differently, or between point-of-care and lab-based testing., Conclusion: Overall, iAg tests have a high pooled specificity but a moderate pooled sensitivity, according to our analysis. The pooled sensitivity increases with lower Ct-values (a proxy for viral load), or within the first week of symptom onset, enabling reliable identification of most COVID-19 cases and highlighting the importance of context in test selection. The study underscores the need for careful evaluation considering performance variations and operational features of iAg tests., (© 2024. The Author(s).)

Perfect, uninterrupted basic life support (BLS) is the key for successful cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OHCA). Time plays an important role in the treatment of OHCA. This applies both to the time until the start of BLS and the reduction of all pauses during resuscitation, especially chest compressions. In 2022, the rate of bystander-CPR showed an absolute increase of 4% compared to previous years. The bystander-CPR rate is currently above 50%. Compared to OHCA in adults, cardiac arrest in children is rare in Germany. In the period from 2007 to 2021, the incidence was 3.08 per 100000 children. In addition, the etiology in children varies depending on the age group. While hypoxia is often the cause of circulatory arrest in younger children, trauma and drowning accidents are the main causes in school-age children. Different additional diagnostic and therapeutic strategies have been evaluated over the last years. Point-of-care ultrasound during resuscitation should only be performed by experienced users. Interrupting chest compressions and thus prolonging the no-flow phases must be avoided. Double sequential external defibrillation after the third shock can successfully terminate refractory ventricular fibrillation. While further studies are needed, emergency medical systems should train their teams to avoid complications. In refractory OHCA, extracorporeal CPR should be considered. In the case of in-hospital cannulation, immediate transport should be weighed against impaired chest compression quality. Therefore, transportation under CPR is only beneficial if there is an indication for further treatment., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen JTG und JW sind Mitglieder des Organisations-Komitees des Deutschen Reanimationsregisters. JTG, LH und JW sind Mit-Organisatoren der Resuscitation Academy Deutschland und Vorstandsmitglieder des Deutschen Zentrums für Reanimationsforschung. SK hat keine Interessenskonflikte., (Thieme. All rights reserved.)

Aim of the Study: Cardiac arrest research has not received as much scientific attention as research on other topics. Here, we aimed to identify cardiac arrest research barriers from the perspective of an international group of early career researchers., Methods: Attendees of the 2022 international masterclass on cardiac arrest registry research accompanied the Global Out-of-Hospital Cardiac Arrest Registry collaborative meeting in Utstein, Norway, and used an adapted hybrid nominal group technique to obtain a diverse and comprehensive perspective. Barriers were identified using a web-based questionnaire and discussed and ranked during an in-person follow-up meeting. After each response was discussed and clarified, barriers were categorized and ranked over two rounds. Each participant scored these from 1 (least significant) to 5 (most significant)., Results: Nine participants generated 36 responses, forming seven overall categories of cardiac arrest research barriers. "Allocated research time" was ranked first in both rounds. "Scientific environment", including appropriate mentorship and support systems, ranked second in the final ranking. "Resources", including funding and infrastructure, ranked third. "Access to and availability of cardiac arrest research data" was the fourth-ranked barrier. This included data from the cardiac arrest registries, medical devices, and clinical studies. Finally, "uniqueness" was the fifth-ranked barrier. This included ethical issues, patient recruitment challenges, and unique characteristics of cardiac arrest., Conclusion: By identifying cardiac arrest research barriers and suggesting solutions, this study may act as a tool for stakeholders to focus on helping early career researchers overcome these barriers, thus paving the road for future research., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. AE, KT, and VK are committee members/representatives of the Young European Resuscitation Council. BM: Member of the European Resuscitation Council and German Resuscitation Council. CM: Member of the European Resuscitation Council and German Resuscitation Council. SO: Member of the European Resuscitation Council and Austrian Resuscitation Council. All other authors state no conflict of interest., (© 2024 The Author(s).)

When performing an aggregate data meta-analysis of a continuous outcome, researchers often come across primary studies that report the sample median of the outcome. However, standard meta-analytic methods typically cannot be directly applied in this setting. In recent years, there has been substantial development in statistical methods to incorporate primary studies reporting sample medians in meta-analysis, yet there are currently no comprehensive software tools implementing these methods. In this paper, we present the metamedian R package, a freely available and open-source software tool for meta-analyzing primary studies that report sample medians. We summarize the main features of the software and illustrate its application through real data examples involving risk factors for a severe course of COVID-19., (© 2023 John Wiley & Sons Ltd.)

Background: Since 2021, international guidelines for cardiopulmonary resuscitation recommend the implementation of so-called "life-saving systems". These systems include smartphone alerting systems (SAS), which enable dispatch centres to alert first responders via smartphone applications, who are in proximity of a suspected out-of-hospital cardiac arrest (OHCA). However, the effect of SAS on survival remains unknown., Aim: The aim is to assess the rate of survival to hospital discharge in adult patients with OHCA not witnessed by emergency medical services (EMS): before and after SAS implementation., Design: Multicentre, prospective, observational, intention-to-treat, pre-post design clinical trial., Population: Adults (aged ≥ 18 years), OHCA not witnessed by EMS, no traumatic cause for cardiac arrest, cardiopulmonary resuscitation initiated or continued by EMS., Setting: Dispatch-centre-based., Outcomes: Primary: survival to hospital discharge. Secondary: time to first compression, rate of basic life support measures before EMS arrival, rate of patients with shockable rhythm at EMS arrival, Cerebral Performance Category at hospital discharge, and duration of hospital stay., Sample Size: Assuming an absolute difference in survival rates to hospital discharge of 4% in the two groups (11% before implementation of the SAS versus 15% after) and 80% power, and a type 1 error rate of 0.05, the required sample size is N  = 1,109 patients per group (at least N  = 2,218 evaluated patients in total)., Conclusions: The HEROES trial will investigate the effects of a SAS on the survival rate after OHCA., Trial Registration: German Clinical Trials Register (DRKS, ID: DRKS00032920)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘MPM is chair of Region der Lebensretter e.V. (non-profit organisation), member of the executive committee of the German Resuscitation Council (GRC), shareholder of SmartResQ ApS, Denmark, and received speaker honoraria by Stryker. JG is board member of Region der Lebensretter e.V. HJB is vice chair of Region der Lebensretter e.V. GT is board member of Region der Lebensretter e.V., secretary of the GRC, and shareholder of Resuscitec GmbH, Freiburg, Germany. JSP is member of Region der Lebensretter e.V. and member of the executive committee of the GRC. All other authors have no conflicts of interest to declare’., (© 2024 The Author(s).)

Self-testing is an effective tool to bridge the testing gap for several infectious diseases; however, its performance in detecting SARS-CoV-2 using antigen-detection rapid diagnostic tests (Ag-RDTs) has not been systematically reviewed. This study aimed to inform WHO guidelines by evaluating the accuracy of COVID-19 self-testing and self-sampling coupled with professional Ag-RDT conduct and interpretation. Articles on this topic were searched until November 7th, 2022. Concordance between self-testing/self-sampling and fully professional-use Ag-RDTs was assessed using Cohen's kappa. Bivariate meta-analysis yielded pooled performance estimates. Quality and certainty of evidence were evaluated using QUADAS-2 and GRADE tools. Among 43 studies included, twelve reported on self-testing, and 31 assessed self-sampling only. Around 49.6% showed low risk of bias. Overall concordance with professional-use Ag-RDTs was high (kappa 0.91 [95% confidence interval (CI) 0.88-0.94]). Comparing self-testing/self-sampling to molecular testing, the pooled sensitivity and specificity were 70.5% (95% CI 64.3-76.0) and 99.4% (95% CI 99.1-99.6), respectively. Higher sensitivity (i.e., 93.6% [95% CI 90.4-96.8] for Ct < 25) was estimated in subgroups with higher viral loads using Ct values as a proxy. Despite high heterogeneity among studies, COVID-19 self-testing/self-sampling exhibits high concordance with professional-use Ag-RDTs. This suggests that self-testing/self-sampling can be offered as part of COVID-19 testing strategies.Trial registration: PROSPERO: CRD42021250706., (© 2023. The Author(s).)

Background: Double sequential external defibrillation (DSED) has demonstrated increased survival with good neurological outcome in a recent randomized controlled trial. DSED has not been studied in patients with extracorporeal cardiopulmonary resuscitation (eCPR)., Case: We present the first case of prehospital eCPR with ongoing refractory ventricular fibrillation (VF), terminated by DSED. After six shocks, return of spontaneous circulation was initially achieved; however, the patient went into recurrent VF. ECPR was performed prehospital, with VF still refractory after three more shocks. DSED successfully terminated VF and showed a further increase in etCO 2 and near-infrared spectroscopy cerebral oximetry values., Conclusion: DSED can be a sufficient strategy for patients in refractory VF while on eCPR and should be evaluated in further studies., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Prehospital care of psychiatric patients often relies on the medical experience of prehospital emergency physicians (PHEPs). The psychiatrists (PSs) involved in the further treatment of psychiatric patients also often rely on their experience. Furthermore, the interaction between PHEPs and PSs is characterized by interaction problems and different approaches in the prehospital care of the psychiatric emergency., Objectives: To analyze the phenomenon of "medical experience" as a cause of possible interaction-related problems and assess its impact on the prehospital decision-making process between prehospital emergency physicians and psychiatrists., Methods: The retrospective data analysis was conducted between November 2022 and March 2023. Medical experience was defined as follows, based on the demographic information collected in the questionnaires: For PHEPs, the period since obtaining the additional qualification in emergency medicine was defined as a surrogate marker of medical experience: (i) inexperienced: < 1 year, (ii) experienced: 1-5 years, (iii) very experienced: > 5 years. For PSs, age in years was used as a surrogate parameter of medical experience: (i) inexperienced: 25-35 years, (ii) experienced: 35-45 years, (iii) very experienced: > 45 years., Results: Inexperienced PSs most frequently expressed anxiety about the psychiatric emergency referred by a PHEP (27.9%). Experienced PHEPs most frequently reported a lack of qualifications in handling the care of psychiatric emergencies (p = 0.002). Very experienced PHEPs were significantly more likely to have a referral refused by the acute psychiatric hospital if an inexperienced PS was on duty (p = 0.01). Experienced PHEPs apply an intravenous hypnotic significantly more often (almost 15%) than PSs of all experience levels (p = 0.001). In addition, very experienced PHEPs sought prehospital phone contact with acute psychiatry significantly more often (p = 0.01)., Conclusion: PHEPs should be aware that the PS on duty may be inexperienced and that treating emergency patients may cause him/her anxiety. On the other hand, PHEPs should be receptive to feedback from PS who have identified a qualification deficiency in them. Jointly developed, individualized emergency plans could lead to better prehospital care for psychiatric emergency patients. Further training in the prehospital management of psychiatric disorders is needed to minimize the existing skills gap among PHEPs in the management of psychiatric disorders., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aim: This work provides an epidemiological overview of out-of-hospital cardiac arrest (OHCA) in children in Germany between 2007 and 2021. We wanted to identify modifiable factors associated with survival., Methods: Data from the German Resuscitation Registry (GRR) were used, and we included patients registered between 1st January 2007 and 31st December 2021. We included children aged between > 7 days and 17 years, where cardiopulmonary resuscitation (CPR) was started, and treatment was continued by emergency medical services (EMS). Incidences and descriptive analyses are presented for the overall cohort and each age group. Multivariate binary logistic regression was performed on the whole cohort to determine the influence of (1) CPR with/without ventilation started by bystander, (2) OHCA witnessed status and (3) night-time on the outcome hospital admission with return of spontaneous circulation (ROSC)., Results: OHCA in children aged < 1 year had the highest incidence of the same age group, with 23.42 per 100 000. Overall, hypoxia was the leading presumed cause of OHCA, whereas trauma and drowning accounted for a high proportion in children aged > 1 year. Bystander-witnessed OHCA and bystander CPR rate were highest in children aged 1-4 years, with 43.9% and 62.3%, respectively. In reference to EMS-started CPR, bystander CPR with ventilation were associated with an increased odds ratio for ROSC at hospital admission after adjusting for age, sex, year of OHCA and location of OHCA., Conclusion: This study provides an epidemiological overview of OHCA in children in Germany and identifies bystander CPR with ventilation as one primary factor for survival. Trial registrations German Clinical Trial Register: DRKS00030989, December 28th 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This review focuses on current developments in post-resuscitation care for adults with an out-of-hospital cardiac arrest (OHCA). As the incidence of OHCA is high and with a low percentage of survival, it remains a challenge to treat those who survive the initial phase and regain spontaneous circulation. Early titration of oxygen in the out-of-hospital phase is not associated with increased survival and should be avoided. Once the patient is admitted, the oxygen fraction can be reduced. To maintain an adequate blood pressure and urine output, noradrenaline is the preferred agent over adrenaline. A higher blood pressure target is not associated with higher rates of good neurological survival. Early neuro-prognostication remains a challenge, and prognostication bundles should be used. Established bundles could be extended by novel biomarkers and methods in the upcoming years. Whole blood transcriptome analysis has shown to reliably predict neurological survival in two feasibility studies. This needs further investigation in larger cohorts.

Background: Hypercoagulability and thrombo-inflammation are the main reasons for death in COVID-19 patients. It is unclear whether there is a difference between D-dimer levels in patients without or with COVID-19 acute respiratory distress syndrome (ARDS)., Methods: We searched PubMed, EMBASE, and ClinicalTrails.gov databases looking for studies reporting D-dimer levels in patients without or with COVID-19 ARDS. Secondary endpoints included length of hospital stay, and mortality data at the longest follow-up available., Results: We included 12 retrospective and 3 prospective studies with overall 2,828 patients, of whom 1,404 (49.6%) had non-COVID-19 ARDS and 1,424 had COVID-19 ARDS. D-dimer levels were not significantly higher in non-COVID-19 ARDS than in COVID-19 ARDS patients (mean 7.65 mg/L vs. mean 6.20 mg/L MD 0.88 [CI: -0.61 to 2.38] p = 0.25; I² = 85%) while the length of hospital stay was shorter (non-COVID-19 mean 37.4 days vs. COVID-19 mean 48.5 days, MD -10.92 [CI: -16.71 to -5.14] p < 0.001; I² = 44%). No difference in mortality was observed: non-COVID-19 ARDS 418/1167 (35.8%) vs. COVID-19 ARDS 467/1201 (38.8%)., Conclusions: We found no difference in the mean D-dimer levels between non-COVID-19 ARDS and COVID-19 ARDS patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tóth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We consider the setting of an aggregate data meta-analysis of a continuous outcome of interest. When the distribution of the outcome is skewed, it is often the case that some primary studies report the sample mean and standard deviation of the outcome and other studies report the sample median along with the first and third quartiles and/or minimum and maximum values. To perform meta-analysis in this context, a number of approaches have recently been developed to impute the sample mean and standard deviation from studies reporting medians. Then, standard meta-analytic approaches with inverse-variance weighting are applied based on the (imputed) study-specific sample means and standard deviations. In this article, we illustrate how this common practice can severely underestimate the within-study standard errors, which results in poor coverage for the pooled mean in common effect meta-analyses and overestimation of between-study heterogeneity in random effects meta-analyses. We propose a straightforward bootstrap approach to estimate the standard errors of the imputed sample means. Our simulation study illustrates how the proposed approach can improve the estimation of the within-study standard errors and consequently improve coverage for the pooled mean in common effect meta-analyses and estimation of between-study heterogeneity in random effects meta-analyses. Moreover, we apply the proposed approach in a meta-analysis to identify risk factors of a severe course of COVID-19.

Background: Despite numerous promising innovations, the chance of survival from sudden cardiac arrest has remained virtually unchanged for decades. Recently, technological advances have been made, user-friendly portable devices have been developed, and advanced invasive procedures have been described that could improve this unsatisfactory situation., Methods: A selective literature search in the core databases with a focus on randomized controlled trials and guidelines., Results: Technical aids, such as feedback systems or automated mechanical cardiopulmonary resuscitation (CPR) devices, can improve chest compression quality. The latter, as well as extracorporeal CPR, might serve as a bridge to treatment (with extracorporeal CPR even as a bridge to recovery). Sonography may be used to improve thoracic compressions on the one hand and to rule out potentially reversible causes of cardiac arrest on the other. Resuscitative endovascular balloon occlusion of the aorta might enhance myocardial and cerebral perfusion. Minithoracostomy, pericardiocentesis, or clamshell thoracotomy might resolve reversible causes of cardiac arrest., Conclusions: It is crucial to identify those patients who may benefit from an advanced or invasive procedure and make the decision to implement the intervention in a timely manner. As with all infrequently performed procedures, sound education and regular training are paramount.

Background: Hyperspectral imaging (HSI) is a novel imaging technology with the ability to assess microcirculatory impairment. We aimed to assess feasibility of performing HSI, a noninvasive, contactless method to assess microcirculatory alterations, during trauma resuscitation care., Methods: This randomized controlled clinical trial was conducted in a dedicated trauma resuscitation room of a level one trauma center. We included adult patients who were admitted to the trauma resuscitation room. Patients were allocated in a 1:1 ratio to the HSI group (intervention) or control group. In addition to the standard of care, patients in the intervention group had two hyperspectral recordings (HSR) of their hand palm taken. Primary outcomes were the treatment duration of the primary survey (until end of ABCDE-evaluation, ultrasound and evaluation by the trauma team) and the total resuscitation room care (until transport to definitive care) as well as the ability to perform measurements from all HSR. Secondary outcomes were analyses from the intervention group compared to HSI measurements of 26 healthy volunteers including an analysis based on the ISS (Injury severity score) (< 16 vs. ≥ 16). Care givers, and those assessing the outcomes were blinded to group assignment., Results: Our final analysis included 51 patients, with 25 and 26 allocated to the control and intervention group, respectively. There was a statistically significant shorter median duration of the primary survey in the control group (03:22 min [Q1-Q3 03:00-03:51]) compared to the intervention group (03:59 min [Q1-Q3 03:29-04:35]) with a difference of -37 s (95% CI -66 to -12). Total resuscitation room care was longer in the control group, but without significance: 60 s (95% CI -60 to 180). From 52 HSI, we were able to perform hyperspectral measurements on all images, with significant differences between injured patients and healthy volunteers., Conclusion: HSI proved to be feasible during resuscitation room care and can provide valuable information on the microcirculatory state. Trial registration DRKS DRKS00024047- www.drks.de . Registered on 13th April 2021., (© 2022. The Author(s).)

Background: Comprehensive information about the accuracy of antigen rapid diagnostic tests (Ag-RDTs) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is essential to guide public health decision makers in choosing the best tests and testing policies. In August 2021, we published a systematic review and meta-analysis about the accuracy of Ag-RDTs. We now update this work and analyze the factors influencing test sensitivity in further detail., Methods and Findings: We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched preprint and peer-reviewed databases for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 until August 31, 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity with reverse transcription polymerase chain reaction (RT-PCR) testing as a reference. To evaluate factors influencing test sensitivity, we performed 3 different analyses using multivariable mixed-effects meta-regression models. We included 194 studies with 221,878 Ag-RDTs performed. Overall, the pooled estimates of Ag-RDT sensitivity and specificity were 72.0% (95% confidence interval [CI] 69.8 to 74.2) and 98.9% (95% CI 98.6 to 99.1). When manufacturer instructions were followed, sensitivity increased to 76.3% (95% CI 73.7 to 78.7). Sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values (97.9% [95% CI 96.9 to 98.9] and 90.6% [95% CI 88.3 to 93.0] for Ct-values <20 and <25, compared to 54.4% [95% CI 47.3 to 61.5] and 18.7% [95% CI 13.9 to 23.4] for Ct-values ≥25 and ≥30) and was estimated to increase by 2.9 percentage points (95% CI 1.7 to 4.0) for every unit decrease in mean Ct-value when adjusting for testing procedure and patients' symptom status. Concordantly, we found the mean Ct-value to be lower for true positive (22.2 [95% CI 21.5 to 22.8]) compared to false negative (30.4 [95% CI 29.7 to 31.1]) results. Testing in the first week from symptom onset resulted in substantially higher sensitivity (81.9% [95% CI 77.7 to 85.5]) compared to testing after 1 week (51.8%, 95% CI 41.5 to 61.9). Similarly, sensitivity was higher in symptomatic (76.2% [95% CI 73.3 to 78.9]) compared to asymptomatic (56.8% [95% CI 50.9 to 62.4]) persons. However, both effects were mainly driven by the Ct-value of the sample. With regards to sample type, highest sensitivity was found for nasopharyngeal (NP) and combined NP/oropharyngeal samples (70.8% [95% CI 68.3 to 73.2]), as well as in anterior nasal/mid-turbinate samples (77.3% [95% CI 73.0 to 81.0]). Our analysis was limited by the included studies' heterogeneity in viral load assessment and sample origination., Conclusions: Ag-RDTs detect most of the individuals infected with SARS-CoV-2, and almost all (>90%) when high viral loads are present. With viral load, as estimated by Ct-value, being the most influential factor on their sensitivity, they are especially useful to detect persons with high viral load who are most likely to transmit the virus. To further quantify the effects of other factors influencing test sensitivity, standardization of clinical accuracy studies and access to patient level Ct-values and duration of symptoms are needed., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CMD is a member of the Editorial Board of PLOS Medicine. CMD also declares a payment from Roche Diagnostics that she accepted as German law requires a manufacturer to pay for the use of data for regulatory purposes. Data was generated as part of an independent evaluation by CMD and team. AM, BE, SC, JAS and SO are employees of FIND, the global alliance for diagnostics.

Background: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs., Methods and Findings: We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers' instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies' heterogeneity in design and reporting., Conclusions: In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CMD is a member of the Editorial Board of PLOS Medicine.

Background: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19., Methods: This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies., Results: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73)., Discussion: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making., Competing Interests: I have read the journal’s policy and none of the authors of this manuscript have a competing interest.

Background: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19., Methods: We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31 st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies., Results: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 - 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73)., Discussion: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors in predicting severe COVID-19 outcomes and will inform decision analytical tools to support clinical decision-making.

Chest Trauma is a complex injury pattern whose diagnostics and therapy demand everything from an emergency response team. Chest trauma subsumes thoracic injuries in all facets from the bounce mark of a seat belt to fatal rollover trauma with contusion or disruption of organs located in the thorax. Possible causes comprise blunt or penetrating trauma, as well as decelerations, chemical and thermal damage. Sonographic assessment according to a protocol plays a major role in diagnosis of underlying conditions and treatment indications. Therapeutic management may include invasive emergency techniques: Decompression of a tension pneumothorax is a fundamental life-saving intervention. Pericardiocentesis seldomly is necessary or possible in order to drain a cardiac tamponade. In case of traumatic cardiac arrest and under defined circumstances, resuscitative thoracotomy may be indicated. The out-of-hospital management may require transfusion of blood components. As with all procedures, which are performed seldomly but under emergency conditions, invasive techniques require clear communication, precise structured working procedures and especially continuous training, team briefing, and debriefing., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)