Assessing the use of minimally invasive self-sampling at home for long-term monitoring of the microbiota within UK families.

Monitoring the presence of commensal and pathogenic respiratory microorganisms is of critical global importance. However, community-based surveillance is difficult because nasopharyngeal swabs are uncomfortable and painful for a wide age range of participants. We designed a methodology for minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. Participants were invited to take part in an exit interview. Thirty-three families completed the study. Sampling using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Multi-niche self-sampling at home can be used by adults and children for longitudinal surveillance of respiratory microorganisms, providing key data for design of future studies.

[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.

[Decision support for patient admission in case of suspicion of COVID-19]. / Entscheidungshilfe zur Patientenzuweisung bei Verdacht auf COVID-19: Für die Anwendung im bayerischen Rettungsdienst.

During a pandemic situation, patients with suspected coronavirus disease (COVID-19) are also treated by emergency medical services (EMS). In order to establish an adequate procedure, a decision aid for the allocation of patients in case of suspicion of COVID-19 has been prepared for the ambulance staff as well as for the emergency physician in the Bavarian EMS. The decision-making aid includes the current guidelines and recommendations on COVID-19. A flowchart in A4 format was chosen for the presentation of the decision aid, which is structured according to the ABCDE scheme (A-Airway, B-Breathing, C-Circulation, D-Disability, E-Environment/Exposure) established in EMS. The flowchart allows patients to be categorized in three stages, based on (vital) parameters and criteria such as risk factors and specific framework conditions. The aim is to provide emergency physicians and ambulance staff with guidance for the assessment of patients and the resulting transport decision with a suitable target clinic if necessary.

Human-Machine Differentiation in Speed and Separation Monitoring for Improved Efficiency in Human-Robot Collaboration.

Human-robot collaborative applications have been receiving increasing attention in industrial applications. The efficiency of the applications is often quite low compared to traditional robotic applications without human interaction. Especially for applications that use speed and separation monitoring, there is potential to increase the efficiency with a cost-effective and easy to implement method. In this paper, we proposed to add human-machine differentiation to the speed and separation monitoring in human-robot collaborative applications. The formula for the protective separation distance was extended with a variable for the kind of object that approaches the robot. Different sensors for differentiation of human and non-human objects are presented. Thermal cameras are used to take measurements in a proof of concept. Through differentiation of human and non-human objects, it is possible to decrease the protective separation distance between the robot and the object and therefore increase the overall efficiency of the collaborative application.

[Full-scale simulation in German medical schools and anesthesia residency programs : Status quo]. / Full-Scale-Simulation in der anästhesiologischen Lehre und Weiterbildung in Deutschland : Gegenwärtiger Stand.

BACKGROUND: Simulation has been increasingly used in medicine. In 2003 German university departments of anesthesiology were provided with a full-scale patient simulator, designated for use with medical students. Meanwhile simulation courses are also offered to physicians and nurses. Currently, the national model curriculum for residency programs in anesthesiology is being revised, possibly to include mandatory simulation training. OBJECTIVES: To assess the status quo of full-scale simulation training for medical school, residency and continuing medical education in German anesthesiology. METHODS: All 38 German university chairs for anesthesiology as well as five arbitrarily chosen non-university facilities were invited to complete an online questionnaire regarding their centers' infrastructure and courses held between 2010 and 2012. RESULTS: The overall return rate was 86 %. In university simulation centers seven non-student staff members, mainly physicians, were involved, adding up to a full-time equivalent of 1.2. All hours of work were paid by 61 % of the centers. The median center size was 100 m2 (range 20-500 m2), equipped with three patient simulators (1-32). Simulators of high or very high fidelity are available at 80 % of the centers. Scripted scenarios were used by 91 %, video debriefing by 69 %. Of the participating university centers, 97 % offered courses for medical students, 81 % for the department's employees, 43 % for other departments of their hospital, and 61 % for external participants. In 2012 the median center reached 46 % of eligible students (0-100), 39 % of the department's physicians (8-96) and 16 % of its nurses (0-56) once. For physicians and nurses from these departments that equals one simulation-based training every 2.6 and 6 years, respectively. 31 % made simulation training mandatory for their residents, 29 % for their nurses and 24 % for their attending physicians. The overall rates of staff ever exposed to simulation were 45 % of residents (8-90), and 30 % each of nurses (10-80) and attendings (0-100). Including external courses the average center trained 59 (4-271) professionals overall in 2012. No clear trend could be observed over the three years polled. The results for the non-university centers were comparable. CONCLUSIONS: Important first steps have been taken to implement full-scale simulation in Germany. In addition to programs for medical students courses for physicians and nurses are available today. To reach everyone clinically involved in German anesthesiology on a regular basis the current capacities need to be dramatically increased. The basis for that to happen will be new concepts for funding, possibly supported by external requirements such as the national model curriculum for residency in anesthesiology.

Colloid, adhesive and release properties of nanoparticular ternary complexes between cationic and anionic polysaccharides and basic proteins like bone morphogenetic protein BMP-2.

Herein we describe an interfacial local drug delivery system for bone morphogenetic protein 2 (BMP-2) based on coatings of polyelectrolyte complex (PEC) nanoparticles (NP). The application horizon is the functionalization of bone substituting materials (BSM) used for the therapy of systemic bone diseases. Nanoparticular ternary complexes of cationic and anionic polysaccharides and BMP-2 or two further model proteins, respectively, were prepared in dependence of the molar mixing ratio, pH value and of the cationic polysaccharide. As further proteins chymotrypsin (CHY) and papain (PAP) were selected, which served as model proteins for BMP-2 due to similar isoelectric points and molecular weights. As charged polysaccharides ethylenediamine modified cellulose (EDAC) and trimethylammonium modified cellulose (PQ10) were combined with cellulose sulphatesulfate (CS). Mixing diluted cationic and anionic polysaccharide and protein solutions according to a slight either anionic or cationic excess charge colloidal ternary dispersions formed, which were cast onto germanium model substrates by water evaporation. Dynamic light scattering (DLS) demonstrated, that these dispersions were colloidally stable for at least one week. Fourier Transform Infrared (FTIR) showed, that the cast protein loaded PEC NP coatings were irreversibly adhesive at the model substrate in contact to HEPES buffer and solely CHY, PAP and BMP-2 were released within long-term time scale. Advantageously, out of the three proteins BMP-2 showed the smallest initial burst and the slowest release kinetics and around 25% of the initial BMP-2 content were released within 14days. Released BMP-2 showed significant activity in the myoblast cells indicating the ability to regulate the formation of new bone. Therefore, BMP-2 loaded PEC NP are suggested as novel promising tool for the functionalization of BSM used for the therapy of systemic bone diseases.

[The basis for well-founded simulations]. / Grundlagen für ein fundiertes Simulationskonzept.

In medical education, simulation is gaining increasing importance for teaching a variety of subjects. A well-founded educational approach is necessary for effective use. In addition to material aspects, simulation environment, curriculum, learning environment, and methods of debriefing have to be considered. The role of a competent instructor should be emphasized and the importance of an elaborate change management process to implement a good concept should not be underestimated.

[Interdisciplinary consensus statement on alternative airway management with supraglottic airway devices in pediatric emergency medicine: Laryngeal mask is state of the art]. / Interdisziplinär konsentierte Stellungnahme zum Atemwegsmanagement mit supraglottischen Atemwegshilfen in der Kindernotfallmedizin: Larynxmaske ist State-of-the-art.

BACKGROUND: Airway management with supraglottic airway devices (SGA) in life-threatening emergencies involving children is becoming increasingly more important. The laryngeal mask (LM) and the laryngeal tube (LT) are devices commonly used for this purpose. This article presents a literature review and consensus statement by various societies on the use of SGA in pediatric emergency medicine. MATERIAL AND METHODS: Literature search in the database PubMed and classification of studies according to the criteria of the Oxford Centre for Evidence-based Medicine levels of evidence. RESULTS: The evidence for successful application of the various types of LM is significantly higher than for LT application. Reports of smaller series of successful applications of LT are currently limited to selected research groups and centers. Insufficient evidence currently exists for the successful application of the LT especially for children below 10 kg body weight and, therefore, its routine use cannot currently be recommended. SGAs used for emergencies should have a possibility for gastric drainage. 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) 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, 1.5, 2, 2.5, 3, 4 and 5) for prehospital and in-hospital emergency use and all users should be regularly trained in its application.

[Better apprehension of errors in the early clinical treatment of the severely injured]. / Fehler in der frühklinischen Schwerverletztenversorgung besser begreifen.

BACKGROUND: Every year preventable adverse events endanger a considerable number of patients. Current guidelines of the Federal Joint Committee require clinical quality management to provide amongst others an independent clinical risk management and a critical incident reporting system (CIRS). Such guidelines increase the pressure to actively deal with errors, even in emergency medicine. Human error is considered to be the main cause of preventable adverse events in high-risk industries, such as aviation. This observation is gladly directly transferred to clinical medicine. OBJECTIVES: This study investigated where the true causes for preventable adverse events during the resuscitation of severely injured patients can be found. METHODS: A non-systematic literature search of the PubMed database was performed. RESULTS: The search identified three recent studies addressing these objectives that revealed human error as the most important cause of preventable adverse events during emergency room resuscitation (88-97%). Errors during resuscitation in the emergency room occur in approximately 10 %. It is striking that such data do not differ greatly from findings described in studies undertaken 20 years ago. One possible explanation might be that the systematic evaluation of medical errors in the emergency room is a weak spot and that too few lessons can be learnt from such incidents. Therefore, this article describes models of error development and outlines methods to collect data for root cause analysis and for clinical risk management. Thus, this review aims at a better understanding of how errors originate and to allow development of strategies to prevent errors from happening again. CONCLUSION: Human error is the most important cause of preventable adverse events during emergency room resuscitation. Presumably, errors occur unintentionally and as a result of situational misjudgment. As such errors have marked consequences on mortality and morbidity of severely injured patients, an extensive risk management is mandatory for the improvement of quality and safety. Appropriate methods to record errors in order to allow a correct root cause analysis according to well-established protocols is a basic prerequisite.

Fast and slow interactions of n-alkanols with human 5-HT3A receptors: Implications for anesthetic mechanisms.

This is part of a continuing patch-clamp study exploring molecular actions of anesthetics and systematically varied related substances on 5-HT3A receptors as prototypes of ligand-gated ion channels. Specifically, n-alkanols, related to but simpler in structure than propofol, were studied to explore the complex actions of this leading intravenous anesthetic. Outside-out patches excised from HEK 293 cells heterologously expressing human 5-HT3A receptors were superfused with even-numbered n-alkanols (ethanol through n-tetradecanol) of different concentrations. Fast solution exchange for varying durations allowed separation of drug actions by their kinetics. Compared with propofol the electrophysiological responses to n-alkanols were not much simpler. n-Alkanols produced fast and slow inhibition or potentiation of current amplitudes, and acceleration of current rise and decay time constants, depending on exposure time, concentration, and chain-length of the drug. Inhibition dominated, characterized by fast and slow processes with time constants separated by two orders of magnitude which were similar for different n-alkanols and for propofol. Absolute interaction energies for ethanol to n-dodecanol (relative to xenon) ranged from -10.8 to -37.3kJmol(-1). No two n-alkanols act completely alike. Potency increases with chain length (until cutoff) mainly because of methylene groups interacting with protein sites rather than because of their tendency to escape from the aqueous phase. Similar wash-in time constants for n-alkanols and propofol suggest similar mechanisms, dominated by the kinetics of conformational state changes rather than by binding reactions.

10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.

Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3-45%; P < 0·01), 19F (21-66%; P < 0·01) and 23F (13-36%; P = 0·02), but not serotypes 6B (24-42%; P = 0·24) and 14 (21-40%; P = 0·06). Correlations between antibodies and memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides.

Effects of opioids on human serotonin transporters.

The serotonin (5-hydroxtryptamine, 5-HT) system plays a role in analgesia and emesis. The aim of this study was to test whether opioids or ketamine inhibit the human 5-HT transporter and whether this increases free plasma 5-HT concentrations. HEK293 cells, stably transfected with the human 5-HT transporter cDNA, were incubated with morphine, hydromorphone, fentanyl, alfentanil, pethidine (meperidine), tramadol, ketamine, and the reference substance citalopram (specific 5-HT transporter inhibitor). The uptake of [(3)H]5-HT was measured by liquid scintillation counting. In a second series of experiments, study drugs were incubated with plasma of ten healthy blood donors and change of 5-HT plasma-concentrations were measured (ELISA). The end point was the inhibition of the 5-HT transporter by different analgesics either in HEK293 cells or in human platelets ex vivo. Tramadol, pethidine, and ketamine suppressed [(3)H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230 µM, respectively. These drugs also prevented 5-HT uptake in platelets with an increase in free plasma 5-HT. Free 5-HT concentrations in human plasma were increased by citalopram 1 µM, tramadol 20 µM, pethidine 30 µM, and ketamine 100 µM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p < 0.005). No change in both experimental settings was observed for the other opioids. Tramadol and pethidine inhibited the 5-HT transporter in HEK293 cells and platelets. This inhibition may contribute to serotonergic effects when these opioids are given in combination, e.g., with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors.

[Rocuronium and sugammadex in emergency medicine: requirements of a muscle relaxant for rapid sequence induction]. / Rocuronium und Sugammadex in der Notfallmedizin : Anforderungen an ein Muskelrelaxans für die "rapid sequence induction"

UNLABELLED: The required characteristics of neuromuscular blockers for rapid sequence induction (RSI) are clearly defined: nearly immediate effectiveness and short duration of effect. These demands are not only necessary for ideal conditions of quick endotracheal intubation without mask-bag intermediate ventilation but are also essential to enable a quick return to sufficient spontaneous breathing in case of a cannot intubate cannot ventilate situation. Until recently only succinylcholine had these characteristics; however, a considerable number of dangerous side effects and contraindications had to be accepted. In 1996, rocuronium was introduced, which was capable of immediately establishing good intubation conditions similar to succinylcholine. However, the median duration of effect is 45-60 min and it therefore contains a risk if the patient cannot be ventilated and oxygenated. Therefore, rocuronium is considered a good alternative but not a complete substitute for succinylcholine. The introduction of sugammadex in 2008 for quick reversal of rocuronium changed matters. Comparative studies from the past 4 years dealing with rocuronium/sugammadex versus uccinylcholine in RSI showed that rocuronium and sugammadex combined enabled a significantly faster return to sufficient spontaneous ventilation in emergency situations and also proved that the use of rocuronium significantly reduced the degree of desaturation during the interval between injection and ventilation postintubation. CONCLUSION: rocuronium used in hospital is a very good substitute for succinylcholine as a neuromuscular blocker during RSI as long as sugammadex is at hand for reversal. It remains to be considered that in a situation with severe problems of the airway and breathing, which are the main preclinical indications for intubation, a forward strategy for ventilation of the patient is the only acceptable way in most cases and the return to spontaneous breathing is not an alternative. Therefore, the value of sugammadex and also of succinylcholine is limited for these situations. Additionally, economic factors such as storage conditions for rocuronium and the cost of sugammadex must also be considered.

Direct effects of morphine but not of fentanyl-type opioids on human 5-HT3A receptors in outside-out patch-clamp studies.

BACKGROUND: The alkaloid morphine is historically the oldest opiate, yet still today it has clinically important uses in analgesic therapies. The main analgesic effect of opioids, including synthetic opioids belonging to the family of 4-anilidopiperidines, is mediated via activation of opioid receptors spread throughout the peripheral and central nervous system. However, morphine acting as a 'dirty' drug also exhibits effects on other receptor systems, e.g., the serotonergic system and its 5-HT3 receptor. Therefore, this study focuses on the interaction of morphine and fentanyl-type opioids (alfentanil, remifentanil and sufentanil) with 5-HT3A receptors. METHODS: Excised outside-out patches from human embryonic kidney-293 cells, stably transfected with the human 5-HT3A receptor cDNA, were used to determine the opioid effects using the patch-clamp technique. RESULTS: Within clinical concentrations, the effects of morphine are concentration-dependent. Morphine reduced current amplitudes, as well as activation and decay time constants. These effects were not competitive. Contrary to these results, all fentanyl-type opioids only exerted effects far above their clinical concentration ranges. These effects were not homogenous but varying. CONCLUSIONS: Morphine is an opioid compound exhibiting special antagonistic interaction with 5-HT3A receptors. This interaction is not shared by the newer synthetic derivatives of the fentanyl-type opioids in the clinical relevant concentration range.