A brain machine interface framework for exploring proactive control of smart environments.

Brain machine interfaces (BMIs) can substantially improve the quality of life of elderly or disabled people. However, performing complex action sequences with a BMI system is onerous because it requires issuing commands sequentially. Fundamentally different from this, we have designed a BMI system that reads out mental planning activity and issues commands in a proactive manner. To demonstrate this, we recorded brain activity from freely-moving monkeys performing an instructed task and decoded it with an energy-efficient, small and mobile field-programmable gate array hardware decoder triggering real-time action execution on smart devices. Core of this is an adaptive decoding algorithm that can compensate for the day-by-day neuronal signal fluctuations with minimal re-calibration effort. We show that open-loop planning-ahead control is possible using signals from primary and pre-motor areas leading to significant time-gain in the execution of action sequences. This novel approach provides, thus, a stepping stone towards improved and more humane control of different smart environments with mobile brain machine interfaces.

Quality indicators in intensive care medicine for Germany - fourth edition 2022.

The measurement of quality indicators supports quality improvement initiatives. The German Interdisciplinary Society of Intensive Care Medicine (DIVI) has published quality indicators for intensive care medicine for the fourth time now. After a scheduled evaluation after three years, changes in several indicators were made. Other indicators were not changed or only minimally. The focus remained strongly on relevant treatment processes like management of analgesia and sedation, mechanical ventilation and weaning, and infections in the ICU. Another focus was communication inside the ICU. The number of 10 indicators remained the same. The development method was more structured and transparency was increased by adding new features like evidence levels or author contribution and potential conflicts of interest. These quality indicators should be used in the peer review in intensive care, a method endorsed by the DIVI. Other forms of measurement and evaluation are also reasonable, for example in quality management. This fourth edition of the quality indicators will be updated in the future to reflect the recently published recommendations on the structure of intensive care units by the DIVI.

The effect of non-invasive ventilation on intra-abdominal pressure.

BACKGROUND: Non-invasive ventilation is a well-established treatment modality in patients with respiratory failure of different aetiologies. A previous case report described how non-invasive ventilation caused gastric distension and intra-abdominal hypertension with subsequent cardio-respiratory arrest and clinical recovery following resuscitative efforts including gastric decompression with a nasogastric tube. METHODS: The aim of this prospective multicentre observational study was to assess the effect of non-invasive ventilation on intra-abdominal pressure. Following informed consent, intra-abdominal pressure and PaCO2 were measured before and after the application of non-invasive ventilation for up to three days in critically ill patients requiring non-invasive ventilation. RESULTS: Thirty-five patients were enrolled; mean (±SD) age of 67.8 (±12.5) years, median (interquartile range) body mass index of 27.9 (24.5-30.0) kg m-2, Acute Physiology and Chronic Health Evaluation II score of 15.8 (±6.4). On admission and after 24 hours of non-invasive ventilation, intra-abdominal pressure was 11.0 (7.5-15.0) mm Hg and 11.0 (8.5-14.5) mm Hg (P = 0.82) and PaCO2 was 44.4 (±11.4) mm Hg and 51.3 (±14.3) mm Hg (P = 0.19), respectively. CONCLUSIONS: The application of non-invasive ventilation was not associated with an increase in intra-abdominal pressure over 72 hours in this small observational study. Thus, it appears that intra-abdominal pressure does not frequently increase when applying non-invasive ventilation in critically ill patients with respiratory failure.

Rabbit neurospheres as a novel in vitro tool for studying neurodevelopmental effects induced by intrauterine growth restriction.

The aim of this study was to develop a rabbit neurosphere culture to characterize differences in basic processes of neurogenesis induced by intrauterine growth restriction (IUGR). A novel in vitro neurosphere culture has been established using fresh or frozen neural progenitor cells from newborn (PND0) rabbit brains. After surgical IUGR induction in pregnant rabbits and cesarean section 5 days later, neural progenitor cells from both control and IUGR groups were isolated and directly cultured or frozen at -80°C. These neural progenitor cells spontaneously formed neurospheres after 7 days in culture. The ability of control and IUGR neurospheres to migrate, proliferate, differentiate to neurons, astrocytes, or oligodendrocytes was compared and the possibility to modulate their responses was tested by exposure to several positive and negative controls. Neurospheres obtained from IUGR brains have a significant impairment in oligodendrocyte differentiation, whereas no significant differences are observed in other basic processes of neurogenesis. This impairment can be reverted by in vitro exposure of IUGR neurospheres to thyroid hormone, which is known to play an essential role in white matter maturation in vivo. Our new rabbit neurosphere model and the results of this study open the possibility to test several substances in vitro as neuroprotective candidates against IUGR induced neurodevelopmental damage while decreasing the number of animals and resources and allowing a more mechanistic approach at a cellular functional level.

The future development of intensive care quality indicators - a methods paper.

Introduction: Medical quality indicators (QI) are important tools in the evaluation of medical quality. Their development is subject to specific methodological requirements, which include practical applicability. This is especially true for intensive care medicine with its complex processes and their interactions. This methods paper presents the status quo and shows necessary methodological developments for intensive care QI. For this purpose, a cooperation with the Association of the Scientific Medical Societies' Institute for Medical Knowledge Management (AWMF-IMWi) was established. Methodology: Review of published German manuals for QI development from guidelines and narrative review of quality indicators with a focus on evidence and consensus-based guideline recommendations. Future methodological adaptations of indicator development for improved operationalization, measurability and pilot testing are presented, and a development process is proposed. Results: The development of intensive care quality indicators in Germany is based on an established process. In the future, additional evaluation criteria (QUALIFY criteria) will be applied to assess the evidence base. In addition, a continuous exchange between the national steering committee of the DIVI responsible for QI development and guideline development groups involved in intensive care medicine is planned. Conclusion: Intensive care quality indicators will have to meet improved methodological requirements in the future by means of an improved development process. Future QI development is intended to improve the structure of the development process, with a focus on scientific evidence and a link to guideline projects. This is intended to achieve the goal of a broad application of QI and to further evaluate its relevance for patient outcome and performance of institutions.

Unexpected NADPH Hydratase Activity in the Nitrile Reductase QueF from Escherichia coli.

The nitrile reductase QueF catalyzes NADPH-dependent reduction of the nitrile group of preQ0 (7-cyano-7-deazaguanine) into the primary amine of preQ1 (7-aminomethyl-7-deazaguanine), a biologically unique reaction important in bacterial nucleoside biosynthesis. Here we have discovered that the QueF from Escherichia coli-its D197A and E89L variants in particular (apparent kcat ≈10-2  min-1 )-also catalyze the slow hydration of the C5=C6 double bond of the dihydronicotinamide moiety of NADPH. The enzymatically C6-hydrated NADPH is a 3.5:1 mixture of R and S forms and rearranges spontaneously through anomeric epimerization (ß→α) and cyclization at the tetrahydronicotinamide C6 and the ribosyl O2. NADH and 1-methyl- or 1-benzyl-1,4-dihydronicotinamide are not substrates of the enzymatic hydration. Mutagenesis results support a QueF hydratase mechanism, in which Cys190-the essential catalytic nucleophile for nitrile reduction-acts as the general acid for protonation at the dihydronicotinamide C5 of NADPH. Thus, the NADPH hydration in the presence of QueF bears mechanistic resemblance to the C=C double bond hydration in natural hydratases.

Modular Neural Mechanisms for Gait Phase Tracking, Prediction, and Selection in Personalizable Knee-Ankle-Foot-Orthoses.

Orthoses for the lower limbs support patients to perform movements that they could not perform on their own. In traditional devices, generic gait models for a limited set of supported movements restrict the patients mobility and device acceptance. To overcome such limitations, we propose a modular neural control approach with user feedback for personalizable Knee-Ankle-Foot-Orthoses (KAFO). The modular controller consists of two main neural components: neural orthosis control for gait phase tracking and neural internal models for gait prediction and selection. A user interface providing online feedback allows the user to shape the control output that adjusts the knee damping parameter of a KAFO. The accuracy and robustness of the control approach were investigated in different conditions including walking on flat ground and descending stairs as well as stair climbing. We show that the controller accurately tracks and predicts the user's movements and generates corresponding gaits. Furthermore, based on the modular control architecture, the controller can be extended to support various distinguishable gaits depending on differences in sensory feedback.

Quality indicators in intensive care medicine for Germany - third edition 2017.

Quality improvement in medicine is depending on measurement of relevant quality indicators. The quality indicators for intensive care medicine of the German Interdisciplinary Society of Intensive Care Medicine (DIVI) from the year 2013 underwent a scheduled evaluation after three years. There were major changes in several indicators but also some indicators were changed only minimally. The focus on treatment processes like ward rounds, management of analgesia and sedation, mechanical ventilation and weaning, as well as the number of 10 indicators were not changed. Most topics remained except for early mobilization which was introduced instead of hypothermia following resuscitation. Infection prevention was added as an outcome indicator. These quality indicators are used in the peer review in intensive care, a method endorsed by the DIVI. A validity period of three years is planned for the quality indicators.

End-of-life decisions in surgical intensive care medicine - the relevance of blood transfusions.

BACKGROUND: End-of-life decisions (EOLDs) are common in the intensive care unit (ICU). EOLDs underlie a dynamic process and limitation of ICU-therapies is often done sequentially. Questionnaire-based and observational studies on medical ICUs and in palliative care reveal blood transfusions as the first therapy physicians withhold as an EOLD. METHODS: To test whether this practice also applies to surgical ICU-patients, in an observational study, all deceased patients (n = 303) admitted to an academic surgical ICU in a three-year period were analyzed for the process of limiting ICU-therapies. RESULTS: Restriction of further surgery (85.4%) and limiting doses of vasopressors (75.8%) were the most frequent forms of limitations in surgical ICU therapies. Surgical patients, who had blood transfusions withheld (44.6%), had more ICU-therapies withheld or withdrawn simultaneously than patients who had transfusions maintained (5 ± 2 vs. 2 ± 1, p < 0.001). Secondary EOLDs and subsequent limitations occurred less frequently in patients who had transfusions withheld with their first EOLD (17.1% vs. 35.6%, p < 0.05). CONCLUSION: Limitation orders for blood transfusions are not a prioritized decision in EOLDs of surgical ICU patients. Withholding blood transfusions correlates with discontinuation of further significant life-support therapies. This suggests that EOLDs to withhold blood transfusions are part of the most advanced limitations of therapy on the surgical ICU.

Early levosimendan administration is associated with decreased mortality after cardiac surgery.

PURPOSE: The aim of this study was to assess the effects on postoperative outcome of levosimendan with respect to timing of its administration in cardiac surgery patients. MATERIALS AND METHODS: Levosimendan administration was triggered by a severely reduced left ventricular systolic function (left ventricular ejection fraction, <35%) and/or signs of a low cardiac output syndrome. A total of 159 patients were retrospectively assigned depending on an early (perioperatively up to the first hour after intensive care unit [ICU] admission) vs late (later than the first hour after ICU admission) start of treatment. RESULTS: Patients receiving levosimendan after the first hour of ICU admission (n = 89) had a significantly increased inhospital (P = .004) and 1-year (P = .027) mortality. Duration of mechanical ventilation (P = .002), incidence of renal dysfunction (P = .002), and need of renal replacement therapy (P = .032) were significantly increased in the late start group. A late start of levosimendan treatment was associated with an odds ratio of 2.258 (95% confidence interval, 1.139-4.550; P = .021) for inhospital mortality and an adjusted hazard ratio of 1.827 (95% confidence interval, 1.155-2.890; P = .010) for 1-year survival. CONCLUSIONS: Findings of this retrospective analysis favor an "early," that is, intraoperatively up to the first hour after ICU admission, start of perioperative levosimendan treatment to maximize its ability to reduce mortality and morbidity.

End-of-life decisions in intensive care medicine-shared decision-making and intensive care unit length of stay.

BACKGROUND: Most deaths on the intensive care unit (ICU) occur after end-of-life decisions (EOLD) have been made. During the decision-making process, responsibility is often shared within the caregiver team and with the patients' surrogates. The intensive care unit length of stay (ICU-LOS) of surgical ICU-patients depends on the primary illness as well as on the past medical history. Whether an increasing ICU-LOS affects the process of EOLD making is unknown. METHODS: A retrospective analysis was conducted on all deceased patients (n = 303) in a 22-bed surgical ICU of a German university medical center. Patient characteristics were compared between surgical patients with an ICU-LOS up to 1 week and those with an ICU-LOS of more than 7 days. RESULTS: Deceased patients with a long ICU-LOS received more often an EOLD (83.2% vs. 63.6%, p = 0.001). Groups did not differ in urgency of admission. Attending intensivists participated in every EOLD. Participation of surgeons was significantly higher in patients with a short ICU-LOS (24.1%, p = 0.003), whereas nurses and the patients' surrogates were involved more frequently in patients with a long ICU-LOS (18.8%, p = 0.021 and 18.9%, p = 0.018, respectively). CONCLUSION: EOLDs of surgical ICU-patients are associated with the ICU-LOS. Reversal of the primary illness leads the early ICU course, while in prolonged ICU-LOS, the patients' predicted will and the expected post-ICU-quality of life gain interest. Nurses and the patients' surrogates participate more frequently in EOLDs with prolonged ICU-LOS. To improve EOLD making on surgical ICUs, the ICU-LOS associated participation of the different decision makers needs further prospective analysis.

Early administration of levosimendan is associated with improved kidney function after cardiac surgery - a retrospective analysis.

BACKGROUND: Several animal studies suggest beneficial effects on kidney function upon administration of levosimendan. As recent data from clinical studies are heterogeneous, we sought to investigate whether levosimendan is associated with improved postoperative kidney function in cardiac surgery patients with respect to timing of its administration. METHODS: Retrospective, single centre, observational analysis at a university hospital in Berlin, Germany. All adult patients without preoperative renal dysfunction that underwent coronary artery bypass grafting and/or valve reconstruction/replacement between 01/01/2007 and 31/12/2011 were considered for analyses. RESULTS: Out of 1.095 included patients, 46 patients were treated with levosimendan due to a severely reduced left ventricular systolic function preoperatively (LVEF < 35%) and/or clinical signs of a low cardiac output syndrome. Sixty-one percent received the drug whilst in the OR, 39% after postoperative intensive care unit admission. When levosimendan was given immediately after anaesthesia induction, creatinine plasma levels (p = 0.009 for nonparametric analysis of longitudinal data in a two-factorial design) and incidence of postoperative renal dysfunction (67.9% vs. 94.4%; p = 0.033) were significantly reduced in contrast to a later start of treatment. In addition, duration of renal replacement therapy was significantly shorter (79 [35;332] vs. 272 [132;703] minutes; p = 0.046) in that group. CONCLUSIONS: Postoperative kidney dysfunction is a common condition in patients under going cardiac surgery. Patients with severely reduced left ventricular function and/or clinical signs of a low cardiac output syndrome who preoperatively presented with a normal kidney function may benefit from an early start of levosimendan administration, i.e. immediately after anaesthesia. TRIAL REGISTRATION: Clinicaltrials.gov-ID: NCT01918618 .

Voluntary peer review as innovative tool for quality improvement in the intensive care unit--a retrospective descriptive cohort study in German intensive care units.

INTRODUCTION: Quality improvement and safety in intensive care are rapidly evolving topics. However, there is no gold standard for assessing quality improvement in intensive care medicine yet. In 2007 a pilot project in German intensive care units (ICUs) started using voluntary peer reviews as an innovative tool for quality assessment and improvement. We describe the method of voluntary peer review and assessed its feasibility by evaluating anonymized peer review reports and analysed the thematic clusters highlighted in these reports. METHODS: Retrospective data analysis from 22 anonymous reports of peer reviews. All ICUs - representing over 300 patient beds - had undergone voluntary peer review. Data were retrieved from reports of peers of the review teams and representatives of visited ICUs. Data were analysed with regard to number of topics addressed and results of assessment questionnaires. Reports of strengths, weaknesses, opportunities and threats (SWOT reports) of these ICUs are presented. RESULTS: External assessment of structure, process and outcome indicators revealed high percentages of adherence to predefined quality goals. In the SWOT reports 11 main thematic clusters were identified representative for common ICUs. 58.1% of mentioned topics covered personnel issues, team and communication issues as well as organisation and treatment standards. The most mentioned weaknesses were observed in the issues documentation/reporting, hygiene and ethics. We identified several unique patterns regarding quality in the ICU of which long-term personnel problems und lack of good reporting methods were most interesting Conclusion: Voluntary peer review could be established as a feasible and valuable tool for quality improvement. Peer reports addressed common areas of interest in intensive care medicine in more detail compared to other methods like measurement of quality indicators.

The German quality indicators in intensive care medicine 2013--second edition.

Quality indicators are key elements of quality management. The quality indicators for intensive care medicine of the German Interdisciplinary Society of Intensive Care Medicine (DIVI) from the year 2010 were recently evaluated when their validity time expired after two years. Overall one indicator was replaced and further three were in part changed. The former indicator I "elevation of head of bed" was replaced by the indicator "Daily multi-professional ward rounds with the documentation of daily therapy goals" and added to the indicator IV "Weaning and other measures to prevent ventilator associated pneumonias (short: Weaning/VAP Bundle)" (VAP = ventilator-associated pneumonia) which aims at the reduction of VAP incidence. The indicator VIII "Documentation of structured relative-/next-of-kin communication" was refined. The indicator X "Direction of the ICU by a specially trained certified intensivist with no other clinical duties in a department" was also updated according to recent study results. These updated quality indicators are part of the Peer Review in intensive care medicine. The next update of the quality indicators is due in 2016.

Catecholamine dosing and survival in adult intensive care unit patients.

BACKGROUND: Volume management and vasopressor support remain the gold standard of critical care for patients with shock. However, prolonged therapy with catecholamines in high doses is associated with a negative patient outcome. The aim of the present study was to analyze the administered levels of catecholamines over time with respect to survival, and to identify a cut-off to allow a prediction of survival. METHODS: Consecutively, 9,108 adult patients during 22 months were evaluated. This group included 1,543 patients treated with epinephrine and/or norepinephrine with any dose at any time. Time and dosages of the applied drugs, the sequential organ failure assessment and acute and chronic health evaluation II scores on admission and daily, the length of intensive care unit stay, and the outcomes were recorded. RESULTS: The non-survivors received higher doses of norepinephrine and epinephrine than the survivors (p < 0.001). The receiver operator characteristic curve for the area under the curve with non-survival as the classifier revealed a cut-off level of 294.33 µg/kg for norepinephrine with a sensitivity of 74.73 % and a specificity of 70.48 % and a cut-off for epinephrine of 70.36 µg/kg with a sensitivity of 83.87 % and a specificity of 72.79 %. Dose-dependent time curves using these cut-off values were calculated. CONCLUSIONS: Survival of patients with prolonged therapy with norepinephrine and epinephrine above the evaluated thresholds is poor, whereas short-term application of high-dose catecholamines is not associated with poor outcome. Therefore, it remains for the individual clinician, patients, and their surrogates to decide whether the use of high doses of vasopressors is appropriate in view of the low probability of survival.

[Peer review in ICU]. / Peer Reviews in der Intensivmedizin.

Peer reviewing in intensive care medicine is an evaluation process that promotes a professional understanding of quality and the exchange of experience in intensive care. It will help integrate evidence-based knowledge into the treatment process at an earlier stage and thus improve the quality of intensive care and intensive nursing care. The process is a learning experience for all involved and is highly satisfying to the participants. The exchange of experience is an essential part of quality control.

Managing end-of-life decision making in intensive care medicine--a perspective from Charité Hospital, Germany.

INTRODUCTION: End-of-life-decisions (EOLD) have become an important part of modern intensive care medicine. With increasing therapeutic possibilities on the one hand and many ICU-patients lacking decision making capacity or an advance directive on the other the decision making process is a major challenge on the intensive care unit (ICU). Currently, data are poor on factors associated with EOLD in Germany. In 2009, a new law on advance directives binding physicians and the patient's surrogate decision makers was enacted in Germany. So far it is unknown if this law influenced proceedings of EOLD making on the ICU. METHODS: A retrospective analysis was conducted on all deceased patients (n = 224) in a 22-bed surgical ICU of a German university medical center from 08/2008 to 09/2010. Patient characteristics were compared between patients with an EOLD and those without an EOLD. Patients with an EOLD admitted before and after change of legislation were compared with respect to frequencies of EOLD performance as well as advance directive rates. RESULTS: In total, 166 (74.1%) of deaths occurred after an EOLD. Compared to patients without an EOLD, comorbidities, ICU severity scores, and organ replacement technology did not differ significantly. EOLDs were shared within the caregiverteam and with the patient's surrogate decision makers. After law enacting, no differences in EOLD performance or frequency of advance directives (8.9% vs. 9.9%; p = 0.807) were observed except an increase of documentation efforts associated with EOLDs (18.7% vs. 43.6%; p<0.001). CONCLUSIONS: In our ICU EOLD proceedings were performed patient-individually. But EOLDs follow a standard of shared decision making within the caregiverteam and the patient's surrogate decision makers. Enacting a law on advance directives has not affected the decision making-process in EOLDs nor has it affected population's advance care planning habits. However, it has led to increased EOLD-associated documentation on the ICU. TRIAL REGISTRATION: [corrected] ClinicalTrials.gov NCT01294189.

Effects of intensivist coverage in a post-anaesthesia care unit on surgical patients' case mix and characteristics of the intensive care unit.

INTRODUCTION: There is an increasing demand for intensive care in hospitals, which can lead to capacity limitations in the intensive care unit (ICU). Due to postponement of elective surgery or delayed admission of emergency patients, outcome may be negatively influenced. To optimize the admission process to intensive care, the post-anaesthesia care unit (PACU) was staffed with intensivist coverage around the clock. The aim of this study is to demonstrate the impact of the PACU on the structure of ICU-patients and the contribution to overall hospital profit in terms of changes in the case mix index for all surgical patients. METHODS: The administrative data of all surgical patients (n = 51,040) 20 months prior and 20 months after the introduction of a round-the-clock intensivist staffing of the PACU were evaluated and compared. RESULTS: The relative number of patients with longer length of stay (LOS) (more than seven days) in the ICU increased after the introduction of the PACU. The average monthly number of treatment days of patients staying less than 24 hours in the ICU decreased by about 50% (138.95 vs. 68.19 treatment days, P <0.005). The mean LOS in the PACU was 0.45 (± 0.41) days, compared to 0.27 (± 0.2) days prior to the implementation. The preoperative times in the hospital decreased significantly for all patients. The case mix index (CMI) per hospital day for all surgical patients was significantly higher after the introduction of a PACU: 0.286 (± 0.234) vs. 0.309 (± 0.272) P <0.001 CMI/hospital day. CONCLUSIONS: The introduction of a PACU and the staffing with intensive care staff might shorten the hospital LOS for surgical patients. The revenues for the hospital, as determined by the case mix index of the patients per hospital day, increased after the implementation of a PACU and more patients can be treated in the same time, due to a better use of resources.