Cardiopulmonary deconditioning and plasma volume loss are not sufficient to provoke orthostatic hypertension.

Orthostatic hypertension, defined by an increase of systolic blood pressure (SBP) of ≥20 mmHg upon standing, harbors an increased cardiovascular risk. We pooled data from two rigorously conducted head-down tilt bedrest studies to test the hypothesis that cardiopulmonary deconditioning and hypovolemia predispose to orthostatic hypertension. With bedrest, peak VO2 decreased by 6 ± 4 mlO2/min/kg (p < 0.0001) and plasma volume by 367 ± 348 ml (p < 0.0001). Supine SBP increased from 127 ± 9 mmHg before to 133 ± 10 mmHg after bedrest (p < 0.0001). In participants with stable hemodynamics following head-up tilt, the incidence of orthostatic hypertension was 2 out of 67 participants before bedrest and 2 out of 57 after bedrest. We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to cause orthostatic hypertension.

Characteristics and special challenges of neonatal emergency transports.

BACKGROUND: As a rule, newborns do not require special medical care. If unexpected complications occur peripartum or postpartum, support from and transport to specialised neonatal hospitals might be needed. METHODS: In a retrospective study, all transport protocols of a supraregional paediatric­neonatological maximum care hospital in northwestern Germany from 01.10.2018 through 30.09.2021 were analysed. The particular focus was on transports of newborns (<7 days) and the leading symptoms that led to contact. RESULTS: A total of 299 patients were included (average age of 15.4 h, 61.6 % males). The average complete transport time was approximately 2 h. Five leading neonatal diseases (respiratory, infectious, asphyxia, cardiac, haematological) were found to represent the causes of >80 % of transfers. Respiratory adaptation disorders are the main reason for transferring a newborn to a centre, whereas asphyxia is the most severe condition. The various symptoms differ in their time of onset, a factor which must be taken into account in practice. Differences were also found between different types of hospitals: while a large proportion of transports were carried out from maternity hospitals (80.6 %), children transported from children's hospitals were generally more severely ill. DISCUSSION: Transfers of neonates, especially from maternity hospitals to neonatal intensive care units due to special neonatal diseases, are not rare. In times of increasingly scarce resources, the effective care of sick or at-risk neonates is essential. For low-population regions, this means professional cooperation between maximum care providers and smaller children's hospitals and maternity-only hospitals.

Impact of daily artificial gravity on autonomic cardiovascular control following 60-day head-down tilt bed rest.

Impaired cardiovascular autonomic control following space flight or immobilization may limit the ability to cope with additional hemodynamic stimuli. Head-down tilt bedrest is an established terrestrial analog for space flight and offers the opportunity to test potential countermeasures for autonomic cardiovascular deconditioning. Previous studies revealed a possible benefit of daily artificial gravity on cardiovascular autonomic control following head-down tilt bedrest, but there is a need for efficiency in a long-term study before an artificial gravity facility would be brought to space. We hypothesized that artificial gravity through short-arm centrifugation attenuates functional adaptions of autonomic function during head-down tilt bed rest. 24 healthy persons (8 women, 33.4 ± 9.3 years, 24.3 ± 2.1 kg/m2) participated in the 60-day head-down tilt bed rest (AGBRESA) study. They were assigned to three groups, 30 min/day continuous, or 6(5 min intermittent short-arm centrifugation, or a control group. We assessed autonomic cardiovascular control in the supine position and in 5 minutes 80° head-up tilt position before and immediately after bed rest. We computed heart rate variability (HRV) in the time (rmssd) and frequency domain, blood pressure variability, and baroreflex sensitivity (BRS). RR interval corrected rmssd was reduced supine (p = 0.0358) and during HUT (p = 0.0161). Heart rate variability in the high-frequency band (hf-RRI; p = 0.0004) and BRS (p < 0.0001) decreased, whereas blood pressure variability in the low-frequency band (lf-SBP, p = 0.0008) increased following bedrest in all groups. We did not detect significant interactions between bedrest and interventions. We conclude that up to daily 30 min of artificial gravity on a short-arm centrifuge with 1Gz at the center of mass do not suffice to prevent changes in autonomic cardiovascular control following 60-day of 6° head-down tilt bed rest. Clinical Trial Registration: https://drks.de/search/en/trial/DRKS00015677, identifier, DRKS00015677.

Evaluating Scalable Supervised Learning for Synthesize-on-Demand Chemical Libraries.

Traditional small-molecule drug discovery is a time-consuming and costly endeavor. High-throughput chemical screening can only assess a tiny fraction of drug-like chemical space. The strong predictive power of modern machine-learning methods for virtual chemical screening enables training models on known active and inactive compounds and extrapolating to much larger chemical libraries. However, there has been limited experimental validation of these methods in practical applications on large commercially available or synthesize-on-demand chemical libraries. Through a prospective evaluation with the bacterial protein-protein interaction PriA-SSB, we demonstrate that ligand-based virtual screening can identify many active compounds in large commercial libraries. We use cross-validation to compare different types of supervised learning models and select a random forest (RF) classifier as the best model for this target. When predicting the activity of more than 8 million compounds from Aldrich Market Select, the RF substantially outperforms a naïve baseline based on chemical structure similarity. 48% of the RF's 701 selected compounds are active. The RF model easily scales to score one billion compounds from the synthesize-on-demand Enamine REAL database. We tested 68 chemically diverse top predictions from Enamine REAL and observed 31 hits (46%), including one with an IC50 value of 1.3 µM.

Effects of daily artificial gravity training on orthostatic tolerance following 60-day strict head-down tilt bedrest.

PURPOSE: Orthostatic intolerance commonly occurs following immobilization or space flight. We hypothesized that daily artificial gravity training through short-arm centrifugation could help to maintain orthostatic tolerance following head-down tilt bedrest, which is an established terrestrial model for weightlessness. METHODS: We studied 24 healthy persons (eight women; age 33.3 ± 9.0 years; BMI 24.3 ± 2.1 kg/m2) who participated in the 60-days head-down tilt bedrest (AGBRESA) study. They were assigned to 30 min/day continuous or 6 × 5 min intermittent short-arm centrifugation with 1Gz at the center of mass or a control group. We performed head-up tilt testing with incremental lower-body negative pressure until presyncope before and after bedrest. We recorded an electrocardiogram, beat-to-beat finger blood pressure, and brachial blood pressure and obtained blood samples from an antecubital venous catheter. Orthostatic tolerance was defined as time to presyncope. We related changes in orthostatic tolerance to changes in plasma volume determined by carbon dioxide rebreathing. RESULTS: Compared with baseline measurements, supine and upright heart rate increased in all three groups following head-down tilt bedrest. Compared with baseline measurements, time to presyncope decreased by 323 ± 235 s with continuous centrifugation, by 296 ± 508 s with intermittent centrifugation, and by 801 ± 354 s in the control group (p = 0.0249 between interventions). The change in orthostatic tolerance was not correlated with changes in plasma volume. CONCLUSIONS: Daily artificial gravity training on a short-arm centrifuge attenuated the reduction in orthostatic tolerance after 60 days of head-down tilt bedrest.

[Update 2022: interdisciplinary statement on airway management with supraglottic airway devices in pediatric emergency medicine-The laryngeal mask is and remains state of the art : Joint statement of the Institute for Emergency Medicine and Medicine Management (INM), the University Clinic Munich, LMU Munich, Germany, the Working Group for Pediatric Critical Care and Emergency Medicine of the German Interdisciplinary Society for Critical Care and Emergency Medicine (DIVI), the Medical Directors of Emergency Medical Services in Bavaria (ÄLRD), the Scientific Working Group for Pediatric Anesthesia (WAKKA) of the German Society for Anesthesiology and Intensive Care Medicine (DGAI), the Scientific Working Group for Emergency Medicine of the German Society for Anesthesiology and Intensive Care Medicine (DGAI) and the Society of Neonatology and Pediatric Critical Care Medicine (GNPI)]. / Update 2022: Interdisziplinäre Stellungnahme zum Atemwegsmanagement mit supraglottischen Atemwegshilfen in der Kindernotfallmedizin ­ die Larynxmaske ist und bleibt State of the Art : Gemeinsame Stellungnahme des Instituts für Notfallmedizin und Medizinmanagement (INM), Klinikum der Universität München, der Sektion Pädiatrische Intensiv- und Notfallmedizin der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI), des Ärztlicher Leiter Rettungsdienst Bayern (ÄLRD Bayern), des Wissenschaftlichen Arbeitskreises Kinderanästhesie (WAKKA) der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI), des Wissenschaftlichen Arbeitskreises Notfallmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI) und der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI).

BACKGROUND: Airway management with supraglottic airway devices (SGA) in life-threatening emergencies in children is increasingly being used. Different specifications of laryngeal masks (LM) and the laryngeal tube (LT) are commonly used devices for this purpose. We present a literature review and interdisciplinary consensus statement of different societies on the use of SGA in pediatric emergency medicine. MATERIAL AND METHODS: Literature review in the PubMed database and classification of studies according to the criteria of the Oxford Centre for Evidence-based Medicine. Levels and consensus finding within the group of authors. RESULTS: The evidence for successful applications of the various types of LM is significantly higher than for LT application. Reported smaller series of successful applications of LT are currently limited to selected research groups and centers. Especially for children below 10 kg body weight there currently exists insufficient evidence for the successful application of the LT and therefore its routine use cannot be recommended. SGAs used for emergencies should have a gastric drainage possibility. DISCUSSION: Considering the scientific data and the large clinical experience with the LM in medical routine and emergency situations in children currently only the LM can be recommended for alternative (i.e., non-intubation) emergency airway management in children. If alternative airway management is part of a local emergency strategy, the LM should be provided in all pediatric sizes (1, 1½, 2, 2½, 3) for out of hospital use and in hospital emergency use and all users should regularly be trained in its application.

[Stroke alarm-Arterial ischemic stroke as one of the most time-critical emergencies in children and adolescents]. / Notfall-Neuropädiatrie ­ Der arteriell ischämische Schlaganfall als einer der zeitkritischsten Notfälle bei Kindern und Jugendlichen.

Arterial ischemic stroke in childhood and adolescence is one of the most time-critical emergencies in pediatrics. Nevertheless, it is often diagnosed with a considerable time delay which may be associated with low awareness, the sometimes nonspecific clinical presentation with a wide variety of differential diagnoses, and less established 'acute care structures'. The revascularisation strategies in adult stroke care are also potential and promising treatment options for children, even if available evidence is still limited. In the post-acute phase, the etiological work-up is complex due to the multitude of risk factors to be considered. But it is essential to identify each child's individual risk profile as it determines secondary prevention, risk of recurrence and outcome. Long-term care in a multiprofessional, interdisciplinary team must take into account the bio-psycho-social aspects to integrate the child into its social and educational, and later professional environment.

[Childhood emergencies-worsening healthcare bottlenecks for children in a systematic long-term analysis of the EMS system in a German metropolis]. / Der Notfall beim Kind ­ zunehmende Versorgungsengpässe für Kinder in einer systematischen Langzeitanalyse des Rettungssystems einer deutschen Metropole.

BACKGROUND: Children have the right to the best possible medical care. The lack of treatment capacity is rising steadily and increasingly leads to forced centralized allocation of patients by the emergency medical services (EMS) to pediatric emergency departments that are, officially, temporarily "closed". AIM: The aim of this study is to present trends in allocation of pediatric emergency patients in greater Munich. MATERIALS AND METHODS: Retrospective analysis of hospital admissions of children < 18 years of age collected from 01 January 2015 to 31 December 2019 by means of the web-based IT system IVENA eHealth (manis IT, Frankfurt) used by the emergency medical services. The focus of the evaluation is on patients in category II, who are likely to require inpatient admission. RESULTS: During the 5­year observation period, a total of 44,549 pediatric patients < 18 years of age (90.6% of total admissions) were admitted to a children's hospital by the ambulance service as category II (SKII) in the Munich metropolitan area. These patients showed an increase in the relative frequency of forced allocations from 1.7% (2015) to 9.4% (2019). Parallel to this, there is an increasing frequency of time intervals over the years in which all children's hospitals were temporarily closed due to lack of treatment availability, especially in the winter half-year. CONCLUSION: In the examined period from 2015 to 2019, there has been a relevant increase in the number of forced allocations to children's hospitals by the emergency medical services in the Munich area. This observed trend is likely to persist over the coming years, in view of current staff shortages and diminishing hospital capacities.

[Debriefing in pediatric emergency care]. / Debriefing in der Kindernotfallversorgung: Grundlage für die Verbesserung der Patientenversorgung.

Communication errors and system problems negatively impact teamwork and shared decision-making and can cause patient harm. However, regular debriefings after critical events positively impact teamwork and patient outcome in pediatric emergency care. Team reflection promotes learning, helps teams to improve and to minimize errors from being repeated in the future. Nevertheless, debriefings in daily practice have not yet become a standard quality marker. Reasons include lack of time, lack of experienced debriefers and lack of support from the key stakeholders. Debriefings can take place at different timepoints with variable duration as needed. Due to the global pandemic, virtual debriefings or hybrid events with a mix of virtual and in-person participation are not only currently relevant but may perhaps also be of future relevance. Debriefings should focus on collaborative learning and future-oriented improvements. Not only life-threatening events but also potentially critical situations such as routine intubations warrant debriefings. Debriefing scripts promote a structured approach and allow even inexperienced moderators to navigate all relevant aspects. In addition to areas of challenge, debriefings should also explore and reinforce positive performance to facilitate learning from success. Debriefers should discuss not only obvious observable accomplishments, but also motivations behind key behaviors. This strategy promotes needs-based learning and focuses on solutions. Helpful strategies include specific questioning techniques, genuine interest and a positive safety culture.

[S2k Guideline - Recommendations for Inpatient Therapy of Patients with COVID-19]. / S2k-Leitlinie ­ Empfehlungen zur stationären Therapie von Patienten mit COVID-19.

Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6 % require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (> 30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.

Recommendations for treatment of critically ill patients with COVID-19 : Version 3 S1 guideline.

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.

[Epistaxis and anticoagulation therapy: an analysis based on health insurance data from Lower Saxony]. / Epistaxis und antithrombotische Medikation: eine Analyse der Daten einer gesetzlichen Krankenversicherung in Niedersachsen.

BACKGROUND: Epistaxis is a common symptom in the medical practice. It is associated with various comorbidities and the use of medications, especially anticoagulants. Despite the high lifetime prevalence, there is limited data on prevalence and possible risk factors. METHODS: The study examines epistaxis care in a large patient population (AOK Lower Saxony) over a ten-year period (2007-2016). Risk factors, age at diagnosis, concomitant medication and comorbidities were analysed and the prevalence in the study period calculated. RESULTS: 162,167 patients visited their doctors between 2007-2016 (308,947 cases). Most patients were treated as outpatients (96.6%) and 54% of patients were men. Over the study period, the prevalence of epistaxis rose by 21% (increase from 8.6 to 9.3 per 1000 insured persons per year) with a comparatively stable prevalence for the inpatient setting (0.2 per 1000 insured persons per year). In 54,105 of all epistaxis cases (17.5%), the use of antithrombotic drugs was recorded (oral anticoagulants: 9.5%). During the study period, increased prescribing of oral anticoagulants (from 7.7% of cases in 2007 to 11.8% in 2016), especially of NOAC was documented (from 0.1% of cases in 2011 to 5.1% in 2016). CONCLUSION: In addition to arterial hypertension, the predominant male sex and the typical age distribution, we found that cases of epistaxis often received anticoagulation therapy. This study showed an increase of epistaxis along with rising prescriptions of NOAC. In contrast, no increase of severe epistaxis cases leading to hospitalization was found.

[Development of a new module for the TraumaRegister DGU® : Better collation of the sequelae of severe injuries during pregnancy]. / Entwicklung eines neuen Moduls für das TraumaRegister DGU® : Folgen schwerer Verletzungen während der Schwangerschaft besser erfassen.

BACKGROUND: Life-threatening injuries during pregnancy are a rare occurrence. The TraumaRegister DGU® (TR-DGU) has been recording whether seriously injured women were pregnant since 2016. This information is not sufficient to enable a differentiated assessment of the quality of care because parameters, such as gestational age, state of pregnancy at discharge and survival of the child are missing. The TraumaRegister working group of the committee on emergency medicine, intensive care and severe trauma management (section NIS) of the German Trauma Society (DGU) therefore came to the conclusion that the fetal outcome or the intactness of the pregnancy after acute treatment is an important measure of the quality of care of pregnant women. They commissioned a task force to work out a suitable data set for a better analysis of such cases. This article presents the so-called fetus module in detail. METHODS: The data set was developed in an interdisciplinary process together with accredited experts from the German Society for Gynecology and Obstetrics (DGGG), the German Society for Perinatal Medicine (DGPM) and the Society for Neonatology and Pediatric Intensive Care Medicine (GNPI). RESULTS: The fetus module comprises 20 parameters describing the pregnancy, the condition of the mother and child on admission and discharge. CONCLUSION: The fetus module will provide important data to make the process and outcome quality of care of severely injured pregnant women measurable and to develop prognostic instruments with which predictions about high-risk constellations for the outcome of mother and child can be made.