Acute Onset of Impaired Consciousness: Diagnostic Evaluation in the Emergency Department.

BACKGROUND: Mortality in patients with acute onset of impaired consciousness is high: as many as 10% do not survive. The spectrum of differential diagnoses is wide, and more than one underlying condition is found in one-third of all cases. In this article, we describe a structured approach to patients with acute onset of impaired consciousness in the emergency department. METHODS: This review is based on pertinent articles retrieved by a selective search of PubMed and on the AWMF guidelines on the most common causes of impairment of consciousness. RESULTS: Impairments of consciousness are classified as quantitative (reduced wakefulness) or qualitative (abnormal content of consciousness). Of all such cases, 45-50% have a primary neurological cause, and approximately 20% are of metabolic or infectious origin. Some cases are due to intoxications, cardiovascular disorders, or psychiatric disorders. Important warning signs ("red flags") in acute onset of impaired consciousness are a hyperacute onset, pupillomotor disturbances, focal neurologic deficits, meningismus, headache, tachycardia and tachypnea (with or without fever), muscle contractions, and skin abnormalities. Patients with severely impaired consciousness should be initially treated in the shock room according to the ABCDE scheme. CONCLUSION: Acute onset of impaired consciousness is a medical emergency. Red flags must be rapidly recognized and treatment initiated immediately. Patients with severely impaired consciousness of new onset and uncertain cause, status epilepticus, lack of protective reflexes, or a new, acute neurologic deficit should be admitted via the resuscitation room.

Analyzing emergency call volume, call durations, and unanswered calls during the first two waves of the COVID-19 pandemic compared to 2019: An observational study of routine data from seven bavarian dispatch centres.

Background: The spread of the COVID-19 pandemic and the corresponding implementation of measures such as stay-at-home orders and curfews had a major impact on health systems, including emergency medical services. This study examined the effect of the pandemic on call volumes, duration of calls and unanswered calls to the emergency number 112. Method: For this retrospective, descriptive study, 986,650 calls to seven emergency dispatch centres in Bavaria between January 01, 2019 and May 31, 2021 were analysed. The absolute number of calls and calls per 100,000 inhabitants as well as the number of unanswered calls are reported. The Mann‒Whitney U test was used to compare mean call durations between 2019 and 2020/2021 during several periods. Results: Call volume declined during the pandemic, especially during periods with strict lockdown restrictions. The largest decline (-12.9 %) occurred during the first lockdown. The largest reduction in the number of emergency calls overall (-25.3 %) occurred on weekends during the second lockdown. Emergency call duration increased, with the largest increase (+13 s) occurring during the "light" lockdown. The number of unanswered calls remained at a similar level as before the pandemic. Conclusion: This study showed that the studied Bavarian dispatch centres experienced lower call volumes and longer call durations during the first two waves of the COVID-19 pandemic (up to May 2021). Longer call durations could be the result of additional questions to identify potentially infectious patients. The fact that the number of unanswered calls hardly changed may indicate that the dispatch centres were not overwhelmed during the study period.

Instance Selection Algorithms for Predictive Modelling in Telehealth Applications.

Telehealth services are becoming more and more popular, leading to an increasing amount of data to be monitored by health professionals. Machine learning can support them in managing these data. Therefore, the right machine learning algorithms need to be applied to the right data. We have implemented and validated different algorithms for selecting optimal time instances from time series data derived from a diabetes telehealth service. Intrinsic, supervised, and unsupervised instance selection algorithms were analysed. Instance selection had a huge impact on the accuracy of our random forest model for dropout prediction. The best results were achieved with a One Class Support Vector Machine, which improved the area under the receiver operating curve of the original algorithm from 69.91 to 75.88 %. We conclude that, although hardly mentioned in telehealth literature so far, instance selection has the potential to significantly improve the accuracy of machine learning algorithms.

Emergence of RNA-guided transcription factors via domestication of transposon-encoded TnpB nucleases.

Transposon-encoded tnpB genes encode RNA-guided DNA nucleases that promote their own selfish spread through targeted DNA cleavage and homologous recombination1-4. This widespread gene family was repeatedly domesticated over evolutionary timescales, leading to the emergence of diverse CRISPR-associated nucleases including Cas9 and Cas125,6. We set out to test the hypothesis that TnpB nucleases may have also been repurposed for novel, unexpected functions other than CRISPR-Cas. Here, using phylogenetics, structural predictions, comparative genomics, and functional assays, we uncover multiple instances of programmable transcription factors that we name TnpB-like nuclease-dead repressors (TldR). These proteins employ naturally occurring guide RNAs to specifically target conserved promoter regions of the genome, leading to potent gene repression in a mechanism akin to CRISPRi technologies invented by humans7. Focusing on a TldR clade found broadly in Enterobacteriaceae, we discover that bacteriophages exploit the combined action of TldR and an adjacently encoded phage gene to alter the expression and composition of the host flagellar assembly, a transformation with the potential to impact motility8, phage susceptibility9, and host immunity10. Collectively, this work showcases the diverse molecular innovations that were enabled through repeated exaptation of genes encoded by transposable elements, and reveals that RNA-guided transcription factors emerged long before the development of dCas9-based editors.

Factors influencing the success and complications of intraosseous access in pediatric patients-a prospective nationwide surveillance study in Germany.

Background: Vascular access is essential for the efficient treatment of critically ill children, but it can be difficult to obtain. Our study was conducted to analyze the feasibility and short-term safety of intraosseous access (IO) use as well as factors influencing its success and the incidence of complications in pediatric emergencies and resuscitation. This dataset of systematically documented intraosseous access attempts constitutes one of the largest published in the literature. Methods: Two-year nationwide prospective surveillance study in Germany from July 2017 to June 2019. Pediatric hospitals anonymously reported the case data of all children aged 28 days to 18 years who arrived with or were treated with an intraosseous access to the German Pediatric Surveillance Unit (GPSU). The main outcomes were the occurrence of complications, overall success and success at the first attempt. The influence of individual factors on outcomes was evaluated using multivariate regression models. Results: A total of 417 patients underwent 549 intraosseous access attempts. The overall rates of success and success at the first attempt were 98.3% and 81.9%, respectively. Approximately 63.6% of patients were successfully punctured within 3 min from the time of indication. Approximately 47.7% of IO access attempts required patient resuscitation. Dislocation [OR 17.74 (5.32, 59.15)] and other complications [OR 9.29 (2.65, 32.55)] occurred more frequently in the prehospital environment. A total of 22.7% of patients experienced minor complications, while 2.5% of patients experienced potentially severe complications. Conclusion: We conclude that intraosseous access is a commonly used method for establishing emergency vascular access in children, being associated with a low (age-dependent) rate of severe complications and providing mostly reliable vascular access despite a relatively high rate of dislocation.

Ambulance deployment without transport: a retrospective difference analysis for the description of emergency interventions without patient transport in Bavaria.

BACKGROUND: Not all patients who call the ambulance service are subsequently transported to hospital. In 2018, a quarter of deployments of an emergency ambulance in Bavaria were not followed by patient transport. This study describes factors that influence patient transport rates. METHOD: This is a retrospective cross-sectional study based on data from all Integrated Dispatch Centres of the Free State of Bavaria in 2018. Included were ambulance deployments without emergency physician involvement, which were subdivided into ambulance deployments without transport and ambulance deployments with transport. The proportion of transported patients were determined for the primary reasons for deployment and for the different community types. On-scene time was compared for calls with and without patient transport. Differences were tested for statistical significance using Chi2 tests and the odds ratio was calculated to determine differences between groups. RESULTS: Of 510,145 deployments, 147,621 (28.9%) could be classified as ambulance deployments without transport and 362,524 (71.1%) as ambulance deployments with transport.The lowest proportion of patients transported was found for activations where the fire brigade was involved ("fire alarm system" 0.6%, "fire with emergency medical services" 5.4%) and "personal emergency response system active alarm" (18.6%). The highest transport rates were observed for emergencies involving "childbirth/delivery" (96.9%) and "trauma" (83.2%). A lower proportion of patients is transported in large cities as compared to smaller cities or rural communities; in large cities, the odds ratio for emergencies without transport is 2.02 [95% confidence interval 1.98-2.06] referenced to rural communites. The median on-scene time for emergencies without transport was 20.8 min (n = 141,052) as compared to 16.5 min for emergencies with transport (n = 362,524). The shortest on-scene times for emergencies without transport were identified for activations related to "fire alarm system" (9.0 min) and "personal emergency response system active alarm" (10.6 min). CONCLUSION: This study indicates that the proportion of patients transported depends on the reason for deployment and whether the emergency location is urban or rural. Particularly low transport rates are found if an ambulance was dispatched in connection with a fire department operation or a personal emergency medical alert button was activated. The on-scene-time of the rescue vehicle is increased for deployments without transport. The study could not provide a rationale for this and further research is needed. Trial registration This paper is part of the study "Rettungswageneinsatz ohne Transport" ["Ambulance deployment without transport"] (RoT), which was registered in the German Register of Clinical Studies under the number DRKS00017758.

Teamwork and mental workload in postsurgical pediatric patient handovers: Prospective effect evaluation of an improvement intervention for OR-PICU patient transitions.

Postsurgical handover of pediatric patients from operating rooms (OR) to pediatric intensive care units (PICU) is a critical step. This transition is susceptible to errors and inefficiencies particularly if poor multidisciplinary teamwork occurs. Despite wide adoption of standardized handover interventions, comprehensive investigations into joint effects for patient care and provider outcomes are scarce. We aimed to improve OR-PICU handovers quality and sought to evaluate the intervention with particular attention to patient care effects and provider outcomes. A prospective, before-after-study design with an interrupted-series and a multi-source, mixed-methods evaluation approach was established. Drawing upon a participative plan-do-study-act approach, a standardized, checklist-based handover process was designed and implemented. For effect assessments, we observed OR-PICU handovers on site (pre implementation: n = 31, post: n = 30), respectively, with standardized expert observation and provider self-report tools (n = 111, n = 110). Setting was a tertiary Pediatric University Hospital. Supplementary qualitative, semi-structured interviews were conducted, and a general inductive content analysis approach was used to identify key facilitators and barriers on implementation. Improvement efforts focused on stepwise implementation of (1) standardized handover process and (2) a checklist for multi-professional OR-PICU handover communication. We observed significant increases in team and patient setup (pre: 79.3%, post: 98.6%, p < .01), enhanced team engagement (pre: 50%, post: 81.7%, p < .01), and comprehensive information transfer by the anesthesia sub-team (pre: 78.6%, post: 87.3%, p < .01). Expert-rated teamwork outcomes were consistently higher, yet self-reported teamwork did not change over time. Provider perceived stress and disruptions did not change, mental workload tended to decrease over time (pre: M = 3.2, post: 2.9, p = .08). Comprehensiveness of post-operative patient information reported by PICU physician increased significantly: pre: 65.9%, post: 76.2%, p < .05. After implementation, providers acknowledged the importance of standardized handover practices and associated benefits for facilitation of information transfer and comprehensiveness. Among reported barriers were obstacles during implementation as well as insufficient consideration of professionals' individual workflow after surgery. CONCLUSION:  A multidisciplinary intervention for postsurgical pediatric patient handovers was associated with improved expert-rated teamwork and fewer omissions of key patient information over time. Inconsistent results were obtained for provider-rated mental workload and teamwork outcomes. The findings contribute to a better understanding concerning the interplay of teamwork and provider cognitions in the course of establishing safe patient transitions in pediatric care. WHAT IS KNOWN: • Transfer of critically ill children conveys significant challenges for interprofessional communication and teamwork. Prospective research into interventions for safe and efficient handover practices of OR PICU patient transitions is necessary. • Checklists are assumed to facilitate cognitive load among providers in acute clinical environments. WHAT IS NEW: • A standardized, checklist-based handover intervention was associated with improvements in team set-up and information transfer. Provider outcomes such as mental workload and stress did not change over time. • The combination of teamwork and provider assessments allows a more nuanced understanding of implementation barriers and sustainable effects in course of OR-PICU handover interventions.

Out-of-hospital cardiac arrest in children: an epidemiological study based on the German Resuscitation Registry identifying modifiable factors for return of spontaneous circulation.

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.

[Pediatric emergency patients in the emergency departments of a German metropolitan region : A retrospective cross-sectional study over a one-year period]. / Pädiatrische Notfallpatienten in den Notaufnahmen einer deutschen Metropolregion : Eine retrospektive Querschnittsstudie über einen 1-Jahres-Zeitraum.

BACKGROUND: To date, no detailed analysis of pediatric emergencies treated in emergency departments (ED) exists. However, in the context of capacity planning and upcoming emergency care reform in Germany, these data are urgently needed. METHODS: Retrospective, multicenter cross-sectional study for the period 01 July 2013 to 01 June 2014 of pediatric cases in emergency departments in Munich. RESULTS: A total of 103,830 cases were analyzed (age: 6.9 ± 5.4 years, boys/girls 55%/45%). A total of 85.9% of cases were treated as outpatients, 12.4% (9.6 per 100,000 children) were admitted to normal and 1.7% (1.0 per 100,000 children) to intensive care. However, the real bed requirements exceeded these guideline numbers, with an absolute requirement of 4.9 ICU beds and 35.1 normal ward beds per day. Load peaks were seen on Wednesday and Friday afternoons and on weekends. Every 8th patient who presented to an ED as a self-referral was treated as an inpatient. CONCLUSION: Capacity planning for inpatient emergency care of pediatric patients requires planning for more beds than can be expected on a population basis. The availability of panel physician care influences patient volume in the EDs. Initial medical assessment tools for treatment need and urgency are needed to distribute patients. The pediatric emergency centers planned as part of the current reform of emergency care must be adequately staffed and financed in order to be able to handle-in close cooperation with statutory health insurance-accredited medical care-the expected demand for care.

Transposon-encoded nucleases use guide RNAs to promote their selfish spread.

Insertion sequences are compact and pervasive transposable elements found in bacteria, which encode only the genes necessary for their mobilization and maintenance1. IS200- and IS605-family transposons undergo 'peel-and-paste' transposition catalysed by a TnpA transposase2, but they also encode diverse, TnpB- and IscB-family proteins that are evolutionarily related to the CRISPR-associated effectors Cas12 and Cas9, respectively3,4. Recent studies have demonstrated that TnpB and IscB function as RNA-guided DNA endonucleases5,6, but the broader biological role of this activity has remained enigmatic. Here we show that TnpB and IscB are essential to prevent permanent transposon loss as a consequence of the TnpA transposition mechanism. We selected a family of related insertion sequences from Geobacillus stearothermophilus that encode several TnpB and IscB orthologues, and showed that a single TnpA transposase was broadly active for transposon mobilization. The donor joints formed upon religation of transposon-flanking sequences were efficiently targeted for cleavage by RNA-guided TnpB and IscB nucleases, and co-expression of TnpB and TnpA led to substantially greater transposon retention relative to conditions in which TnpA was expressed alone. Notably, TnpA and TnpB also stimulated recombination frequencies, surpassing rates observed with TnpB alone. Collectively, this study reveals that RNA-guided DNA cleavage arose as a primal biochemical activity to bias the selfish inheritance and spread of transposable elements, which was later co-opted during the evolution of CRISPR-Cas adaptive immunity for antiviral defence.

Recommendations on the structure, personal, and organization of intensive care units.

Background: Intensive care units (ICU) are central facilities of medical care in hospitals world-wide and pose a significant financial burden on the health care system. Objectives: To provide guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units. Design and setting: Development of recommendations based on a systematic literature search and a formal consensus process from a group of multidisciplinary and multiprofessional specialists from the German Interdisciplinary Association of Intensive Care and Emergency Medicine (DIVI). The grading of the recommendation follows the report from an American College of Chest Physicians Task Force. Results: The recommendations cover the fields of a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, qualitative and quantitative requirements of physicians and nurses as well as staffing with physiotherapists, pharmacists, psychologists, palliative medicine and other specialists, all adapted to the 3 levels of ICUs. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied. Conclusion: This document provides a detailed framework for organizing and planning the operation and construction/renovation of ICUs.

Systemic review of age brackets in pediatric emergency medicine literature and the development of a universal age classification for pediatric emergency patients - the Munich Age Classification System (MACS).

Currently arbitrary, inconsistent and non-evidence-based age cutoffs are used in the literature to classify pediatric emergencies. None of these classifications have valid medical rationale. This leads to confusion and poor comparability of the different study results. To clarify this problem, this paper presents a systematic review of the commonly used age limits from 115 relevant articles. In the literature search 6226 articles were screened. To be included, the articles had to address the following three topics: "health services research in emergency medicine", "pediatrics" and "age as a differentiator". Physiologic and anatomic principles with reference to emergency medicine were used to solve the problem to create a medically based age classification for the first time.The Munich Age Classification System (MACS) presented in this paper is thus consistent with previous literature and is based on medical evidence. In the future, MAC should lead to ensure that a uniform classification is used. This will allow a better comparability of study results and enable meta-analyses across studies.

Trends in Pediatric Mild Traumatic Brain Injury During COVID-19-Related Lockdown-A Single-Center Study.

BACKGROUND: A relevant number of visits to pediatric emergency departments (pED) are associated with mild traumatic brain injury (mTBI). On March 16, 2020, the Bavarian government declared a first full lockdown (LD) related to the coronavirus (COVID-19) pandemic. AIM: The aim of the study was to investigate the impact of LD on pediatric mTBI. METHODS: Retrospective chart review of presentations to a pED due to mTBI. Study periods covered LD (03/17/2020 through 05/05/2020) and the same time in 2017, 2018, and 2019 as reference period (RP). Comparative analyses were performed by Chi-square or Fisher's exact test. RESULTS: Numbers of mTBI cases decreased by half. Age distribution did not differ. A significantly higher proportion of mTBI were related to falls at home (p = 0.001). Further, a higher rate of hospital admissions (p = 0.03), a higher proportion of intensive care unit admissions (p = 0.001), a longer duration of hospital stay (p = 0.02), and a higher rate of intracranial pathologies on neuroimaging were observed during LD (p = 0.007). CONCLUSION: The decrease in mTBI presentations is likely due to an absolute decrease in numbers related to the LD measures, combined with a hesitation to present very minor mTBI to the hospital, because of fear of being infected or not to put additional strain on the healthcare system during this healthcare crisis. On the other hand, data of those that presented with mTBI tend to reflect the more severe spectrum of mTBI.

[DIVI-Recommendations on the infrastruture of adult intensive care units]. / DIVI-Empfehlung zur Struktur und Ausstattung von Intensivstationen 2022 (Erwachsene).

This document on the Structure and Equipment for Intensive Care Units of the German Association for Intensive and Emergency Care (DIVI) aims at providing guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units. The recommendations are based on a systematic literature search and a formal consensus process from a group of multi-disciplinary and multiprofessional specialists from the DIVI. The recommendations comprise a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, the staffing requirement of physicians, nurses, physiotherapists, pharmacists, psychologists, and other specialists. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied.

Transposon-encoded nucleases use guide RNAs to selfishly bias their inheritance.

Insertion sequences (IS) are compact and pervasive transposable elements found in bacteria, which encode only the genes necessary for their mobilization and maintenance. IS 200 /IS 605 elements undergo 'peel-and-paste' transposition catalyzed by a TnpA transposase, but intriguingly, they also encode diverse, TnpB- and IscB-family proteins that are evolutionarily related to the CRISPR-associated effectors Cas12 and Cas9, respectively. Recent studies demonstrated that TnpB-family enzymes function as RNA-guided DNA endonucleases, but the broader biological role of this activity has remained enigmatic. Here we show that TnpB/IscB are essential to prevent permanent transposon loss as a consequence of the TnpA transposition mechanism. We selected a family of related IS elements from Geobacillus stearothermophilus that encode diverse TnpB/IscB orthologs, and showed that a single TnpA transposase was active for transposon excision. The donor joints formed upon religation of IS-flanking sequences were efficiently targeted for cleavage by RNA-guided TnpB/IscB nucleases, and co-expression of TnpB together with TnpA led to significantly greater transposon retention, relative to conditions in which TnpA was expressed alone. Remarkably, TnpA and TnpB/IscB recognize the same AT-rich transposon-adjacent motif (TAM) during transposon excision and RNA-guided DNA cleavage, respectively, revealing a striking convergence in the evolution of DNA sequence specificity between collaborating transposase and nuclease proteins. Collectively, our study reveals that RNA-guided DNA cleavage is a primal biochemical activity that arose to bias the selfish inheritance and spread of transposable elements, which was later co-opted during the evolution of CRISPR-Cas adaptive immunity for antiviral defense.