Violence against healthcare professionals in intensive care units: a systematic review and meta-analysis of frequency, risk factors, interventions, and preventive measures.

BACKGROUND: To assess the frequency, risk factors, consequences, and prevention of violence against healthcare workers in intensive care units. METHODS: PubMed, Scopus, Google Scholar, EMBASE, Cochrane, and Web of Science were searched for studies on violence against healthcare workers in adult intensive care units. Risk factors, patient characteristics, and implications for healthcare workers were collected. Study quality, bias, and level of evidence were assessed using established tools. RESULTS: Seventy-five studies with 139,533 healthcare workers from 32 countries were included. The overall median frequency of violence was 51% (IQR 37-75%). Up to 97% of healthcare workers experienced verbal violence, and up to 82% were victims of physical violence. Meta-analysis of frequency revealed an average frequency of 31% (95% CI 22-41%) for physical violence, 57% for verbal violence (95% CI 48-66%), and 12% for sexual violence (95% CI 4-23%). Heterogeneity was high according to the I2 statistics. Patients were the most common perpetrators (median 56%), followed by visitors (median 22%). Twenty-two studies reported increased risk ratios of up to 2.3 or odds ratios of up to 22.9 for healthcare workers in the ICU compared to other healthcare workers. Risk factors for experiencing violence included young age, less work experience, and being a nurse. Patients who exhibited violent behavior were often male, older, and physically impaired by drugs. Violence was underreported in up to 80% of cases and associated with higher burnout rates, increased anxiety, and higher turnover intentions. Overall the level of evidence was low. CONCLUSIONS: Workplace violence is frequent and underreported in intensive care units, with potential serious consequences for healthcare workers, calling for heightened awareness, screening, and preventive measures. The potential risk factors for violence should be further investigated. SYSTEMATIC REVIEW REGISTRATION: The protocol for this review was registered with Prospero on January 15, 2023 (ID CRD42023388449).

Separation of responsive and unresponsive patients under clinical conditions: comparison of symbolic transfer entropy and permutation entropy.

Electroencephalogram (EEG)-based monitoring during general anesthesia may help prevent harmful effects of high or low doses of general anesthetics. There is currently no convincing evidence in this regard for the proprietary algorithms of commercially available monitors. The purpose of this study was to investigate whether a more mechanism-based parameter of EEG analysis (symbolic transfer entropy, STE) can separate responsive from unresponsive patients better than a strictly probabilistic parameter (permutation entropy, PE) under clinical conditions. In this prospective single-center study, the EEG of 60 surgical ASA I-III patients was recorded perioperatively. During induction of and emergence from anesthesia, patients were asked to squeeze the investigators' hand every 15s. Time of loss of responsiveness (LoR) during induction and return of responsiveness (RoR) during emergence from anesthesia were registered. PE and STE were calculated at -15s and +30s of LoR and RoR and their ability to separate responsive from unresponsive patients was evaluated using accuracy statistics. 56 patients were included in the final analysis. STE and PE values decreased during anesthesia induction and increased during emergence. Intra-individual consistency was higher during induction than during emergence. Accuracy values during LoR and RoR were 0.71 (0.62-0.79) and 0.60 (0.51-0.69), respectively for STE and 0.74 (0.66-0.82) and 0.62 (0.53-0.71), respectively for PE. For the combination of LoR and RoR, values were 0.65 (0.59-0.71) for STE and 0.68 (0.62-0.74) for PE. The ability to differentiate between the clinical status of (un)responsiveness did not significantly differ between STE and PE at any time. Mechanism-based EEG analysis did not improve differentiation of responsive from unresponsive patients compared to the probabilistic PE.Trial registration: German Clinical Trials Register ID: DRKS00030562, November 4, 2022, retrospectively registered.

Spectral and Entropic Features Are Altered by Age in the Electroencephalogram in Patients under Sevoflurane Anesthesia.

BACKGROUND: Preexisting factors such as age and cognitive performance can influence the electroencephalogram (EEG) during general anesthesia. Specifically, spectral EEG power is lower in elderly, compared to younger, subjects. Here, the authors investigate age-related changes in EEG architecture in patients undergoing general anesthesia through a detailed examination of spectral and entropic measures. METHODS: The authors retrospectively studied 180 frontal EEG recordings from patients undergoing general anesthesia, induced with propofol/fentanyl and maintained by sevoflurane at the Waikato Hospital in Hamilton, New Zealand. The authors calculated power spectral density and normalized power spectral density, the entropic measures approximate and permutation entropy, as well as the beta ratio and spectral entropy as exemplary parameters used in current monitoring systems from segments of EEG obtained before the onset of surgery (i.e., with no noxious stimulation). RESULTS: The oldest quartile of patients had significantly lower 1/f characteristics (P < 0.001; area under the receiver operating characteristics curve, 0.84 [0.76 0.92]), indicative of a more uniform distribution of spectral power. Analysis of the normalized power spectral density revealed no significant impact of age on relative alpha (P = 0.693; area under the receiver operating characteristics curve, 0.52 [0.41 0.63]) and a significant but weak effect on relative beta power (P = 0.041; area under the receiver operating characteristics curve, 0.62 [0.52 0.73]). Using entropic parameters, the authors found a significant age-related change toward a more irregular and unpredictable EEG (permutation entropy: P < 0.001, area under the receiver operating characteristics curve, 0.81 [0.71 0.90]; approximate entropy: P < 0.001; area under the receiver operating characteristics curve, 0.76 [0.66 0.85]). With approximate entropy, the authors could also detect an age-induced change in alpha-band activity (P = 0.002; area under the receiver operating characteristics curve, 0.69 [0.60 78]). CONCLUSIONS: Like the sleep literature, spectral and entropic EEG features under general anesthesia change with age revealing a shift toward a faster, more irregular, oscillatory composition of the EEG in older patients. Age-related changes in neurophysiological activity may underlie these findings however the contribution of age-related changes in filtering properties or the signal to noise ratio must also be considered. Regardless, most current EEG technology used to guide anesthetic management focus on spectral features, and improvements to these devices might involve integration of entropic features of the raw EEG.

Relationship of critical dynamics, functional connectivity, and states of consciousness in large-scale human brain networks.

Recent modeling and empirical studies support the hypothesis that large-scale brain networks function near a critical state. Similar functional connectivity patterns derived from resting state empirical data and brain network models at criticality provide further support. However, despite the strong implication of a relationship, there has been no principled explanation of how criticality shapes the characteristic functional connectivity in large-scale brain networks. Here, we hypothesized that the network science concept of partial phase locking is the underlying mechanism of optimal functional connectivity in the resting state. We further hypothesized that the characteristic connectivity of the critical state provides a theoretical boundary to quantify how far pharmacologically or pathologically perturbed brain connectivity deviates from its critical state, which could enable the differentiation of various states of consciousness with a theory-based metric. To test the hypothesis, we used a neuroanatomically informed brain network model with the resulting source signals projected to electroencephalogram (EEG)-like sensor signals with a forward model. Phase lag entropy (PLE), a measure of phase relation diversity, was estimated and the topography of PLE was analyzed. To measure the distance from criticality, the PLE topography at a critical state was compared with those of the EEG data from baseline consciousness, isoflurane anesthesia, ketamine anesthesia, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. We demonstrate that the partial phase locking at criticality shapes the functional connectivity and asymmetric anterior-posterior PLE topography, with low (high) PLE for high (low) degree nodes. The topographical similarity and the strength of PLE differentiates various pharmacologic and pathologic states of consciousness. Moreover, this model-based EEG network analysis provides a novel metric to quantify how far a pharmacologically or pathologically perturbed brain network is away from critical state, rather than merely determining whether it is in a critical or non-critical state.

The social insectivore: Peer and expert influence affect consumer evaluations of insects as food.

As conventional animal production is a significant contributor to anthropogenic climate change, eating of insects in Western markets has been primarily discussed from an environmental perspective. Following advances in food technology and regulation, edible insects are an emerging research topic not only in environmental sciences, but also in consumer research. To contribute to this rising interest, the present research presents consumer psychological drivers to promote insect consumption based on research on social influence. Two experiments that assessed the influence of peer (Study 1) as well as expert influence (Study 2) on acceptance indicators suggest that both types of influence are significantly associated with acceptance of insects as foods. Study 2 further reveals that the proposed effect of expert influence on acceptance of insects is moderated by insect-based disgust sensitivity in a way that expert influence is stronger for consumers low in insect-based disgust sensitivity. Taken together, our research shows that managing expectations via social influence can be an important driver to increase the adoption of insects in Western markets.

Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures.

Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles, paralleling responses to adjuvant-containing vaccines in vivo Age-specific in vitro modeling coupled with proteomics may provide fresh insight into the ontogeny of adjuvant action thereby informing targeted adjuvanted vaccine development for distinct age groups.

Placental Proteomics Reveal Insights into Fetal Alcohol Spectrum Disorders.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) describe many of the well-known neurodevelopmental deficits afflicting children exposed to alcohol in utero. The effects of alcohol on the maternal-fetal interface, especially the placenta, have been less explored. We herein hypothesized that chronic binge alcohol exposure during pregnancy significantly alters the placental protein profile in a rat FASD model. METHODS: Pregnant rats were orogastrically treated daily with alcohol (4.5 g/kg, gestational day [GD] 5 to 10; 6.0 g/kg, GD 11 to 19) or 50% maltose dextrin (isocalorically matched pair-fed controls). On GD 20, placentae were collected, flash-frozen, and stored until tissues were homogenized. Protein lysates were denatured, reduced, captured on a 10-kDa spin filter, and digested. Peptides were eluted, reconstituted, and analyzed by a Q Exactive™ Hybrid Quadrupole-Orbitrap™ mass spectrometer. RESULTS: Mass spectrometry (MS) analysis identified 2,285 placental proteins based on normalized spectral counts and 2,000 proteins by intensity-based absolute quantification. Forty-five placental proteins were significantly (p < 0.05) altered by gestational alcohol exposure by both quantification approaches. These included proteins directly related to alcohol metabolism; specific isoforms of alcohol dehydrogenase and aldehyde dehydrogenase were up-regulated in the alcohol group. Ingenuity analysis identified ethanol degradation as the most significantly altered canonical pathway in placenta, and fetal/organ development as most altered function, with increased risk for metabolic, neurological, and cardiovascular diseases. Physiological roles of the significantly altered proteins were related to early pregnancy adaptations, implantation, gestational diseases, fetal organ development, neurodevelopment, and immune functions. CONCLUSIONS: We conclude that the placenta is a valuable organ not only to understand FASD etiology but it may also serve as a diagnostic tool to identify novel biomarkers for detecting the outcome of fetal alcohol exposure. Placental MS analysis can offer sophisticated insights into identifying alcohol metabolism-related enzymes and regulators of fetal development.

MStern Blotting-High Throughput Polyvinylidene Fluoride (PVDF) Membrane-Based Proteomic Sample Preparation for 96-Well Plates.

We describe a 96-well plate compatible membrane-based proteomic sample processing method, which enables the complete processing of 96 samples (or multiples thereof) within a single workday. This method uses a large-pore hydrophobic PVDF membrane that efficiently adsorbs proteins, resulting in fast liquid transfer through the membrane and significantly reduced sample processing times. Low liquid transfer speeds have prevented the useful 96-well plate implementation of FASP as a widely used membrane-based proteomic sample processing method. We validated our approach on whole-cell lysate and urine and cerebrospinal fluid as clinically relevant body fluids. Without compromising peptide and protein identification, our method uses a vacuum manifold and circumvents the need for digest desalting, making our processing method compatible with standard liquid handling robots. In summary, our new method maintains the strengths of FASP and simultaneously overcomes one of the major limitations of FASP without compromising protein identification and quantification.

Drug-induced sleep endoscopy with target-controlled infusion using propofol and monitored depth of sedation to determine treatment strategies in obstructive sleep apnea.

BACKGROUND: Drug-induced sleep endoscopy (DISE) has become an important diagnostic examination tool in the treatment decision process for surgical therapies in the treatment of obstructive sleep apnea (OSA). Currently, there is a variety of regimes for the performance of DISE, which renders comparison and assessment across results difficult. It remains unclear how the different regimes influence the findings of the examination and the resulting conclusions and treatment recommendations. This study aimed to investigate the correlation between increasing levels of sedation (i.e., light, medium, and deep) induced by propofol using a target-controlled infusion (TCI) pump, with the obstruction patterns at the levels of the velum, oropharynx, tongue base, and epiglottis (i.e., VOTE classification). A second goal was the establishment of a sufficient sedation level to enable a reliable decision regarding treatment recommendations. MATERIAL AND METHODS: Forty-three patients with OSA underwent a DISE procedure using propofol TCI. Three levels of sedation were defined, depending on entropy levels and assessment of sedation: light sedation, medium sedation, and deep sedation. The evaluation of the upper airway at each level, with increasing sedation, was documented using the VOTE classification. The elapsed time at which each assessment was performed was recorded. RESULTS: Upper airway changes occurred and were measured throughout the DISE procedure. Clinically useful determinations of airway closure occurred at medium sedation; this level of sedation was most probably achieved with a blood propofol concentration of 3.2 µg/ml. In all 43 patients, definite treatment decisions could be made at medium sedation level. Increasing sedation did not result in changes in the treatment decision. CONCLUSIONS: Changes in upper airway collapse during DISE with propofol TCI occur at levels of medium sedation. Decisions regarding surgical treatment could be made at this level of sedation. CLINICAL TRIAL NAME: Upper Airway Collapse in Patients with Obstructive Sleep Apnea Syndrome by Drug Induced Sleep Endoscopy (URL: https://clinicaltrials.gov/ct2/results?term=NCT02588300&Search=Search ) REGISTRATION NUMBER: NCT02588300.

The interrelationships of birthweight, inflammation and body composition in healthy adults.

BACKGROUND: Lower birthweight is associated with an increased risk of cardiovascular diseases and diabetes. We hypothesized that inflammation and body fat may be potential mediators for these inverse relationships. MATERIALS AND METHODS: Healthy adults aged 25-41 years were enrolled in a prospective population-based cohort study in the Principality of Liechtenstein. Main exclusion criteria were diabetes, overt cardiovascular disease or a body mass index > 35 kg/m(2) . Birthweight was self-reported by the study participants. White blood cell (WBC) count and high-sensitivity C-reactive protein (hs-CRP) levels were assayed from fresh blood samples. Body composition was determined by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships between birthweight, inflammation and body composition. RESULTS: Our sample consisted of 1774 participants (53·4% females) with a median age of 37 years. Median birthweight was 3355 g. In multivariable models, we found an inverse relationship of birthweight with hs-CRP levels (ß -0·010 (95% CI -0·02; -0·002), P = 0·01) and WBC count (ß -0·002 (95% CI -0·004; -0·0002), P = 0·03). Additional adjustment for body fat mass attenuated these relationships (ß -0·008 (95% CI -0·02; 0·0003), P = 0·06 for hs-CRP levels and (ß -0·002 (95% CI -0·004; 0·0006), P = 0·16 for WBC count. Body fat mass itself was strongly associated with birthweight (ß -0·06 (95% CI -0·10; -0·03), P < 0·0001). CONCLUSION: Birthweight is inversely associated with inflammation in adulthood. This relationship may be mediated by an elevated body fat mass among individuals with lower birthweight.

Neural Correlates of Sevoflurane-induced Unconsciousness Identified by Simultaneous Functional Magnetic Resonance Imaging and Electroencephalography.

BACKGROUND: The neural correlates of anesthetic-induced unconsciousness have yet to be fully elucidated. Sedative and anesthetic states induced by propofol have been studied extensively, consistently revealing a decrease of frontoparietal and thalamocortical connectivity. There is, however, less understanding of the effects of halogenated ethers on functional brain networks. METHODS: The authors recorded simultaneous resting-state functional magnetic resonance imaging and electroencephalography in 16 artificially ventilated volunteers during sevoflurane anesthesia at burst suppression and 3 and 2 vol% steady-state concentrations for 700 s each to assess functional connectivity changes compared to wakefulness. Electroencephalographic data were analyzed using symbolic transfer entropy (surrogate of information transfer) and permutation entropy (surrogate of cortical information processing). Functional magnetic resonance imaging data were analyzed by an independent component analysis and a region-of-interest-based analysis. RESULTS: Electroencephalographic analysis showed a significant reduction of anterior-to-posterior symbolic transfer entropy and global permutation entropy. At 2 vol% sevoflurane concentrations, frontal and thalamic networks identified by independent component analysis showed significantly reduced within-network connectivity. Primary sensory networks did not show a significant change. At burst suppression, all cortical networks showed significantly reduced functional connectivity. Region-of-interest-based thalamic connectivity at 2 vol% was significantly reduced to frontoparietal and posterior cingulate cortices but not to sensory areas. CONCLUSIONS: Sevoflurane decreased frontal and thalamocortical connectivity. The changes in blood oxygenation level dependent connectivity were consistent with reduced anterior-to-posterior directed connectivity and reduced cortical information processing. These data advance the understanding of sevoflurane-induced unconsciousness and contribute to a neural basis of electroencephalographic measures that hold promise for intraoperative anesthesia monitoring.

Advancing Urinary Protein Biomarker Discovery by Data-Independent Acquisition on a Quadrupole-Orbitrap Mass Spectrometer.

The promises of data-independent acquisition (DIA) strategies are a comprehensive and reproducible digital qualitative and quantitative record of the proteins present in a sample. We developed a fast and robust DIA method for comprehensive mapping of the urinary proteome that enables large scale urine proteomics studies. Compared to a data-dependent acquisition (DDA) experiments, our DIA assay doubled the number of identified peptides and proteins per sample at half the coefficients of variation observed for DDA data (DIA = ∼8%; DDA = ∼16%). We also tested different spectral libraries and their effects on overall protein and peptide identifications and their reproducibilities, which provided clear evidence that sample type-specific spectral libraries are preferred for reliable data analysis. To show applicability for biomarker discovery experiments, we analyzed a sample set of 87 urine samples from children seen in the emergency department with abdominal pain. The whole set was analyzed with high proteome coverage (∼1300 proteins/sample) in less than 4 days. The data set revealed excellent biomarker candidates for ovarian cyst and urinary tract infection. The improved throughput and quantitative performance of our optimized DIA workflow allow for the efficient simultaneous discovery and verification of biomarker candidates without the requirement for an early bias toward selected proteins.

Drowning and Nonfatal Drowning in Children and Adolescents: A Subsequent Retrospective Data Analysis.

Fatal and nonfatal drowning are among the leading causes of death and lifelong severe neurological impairment among children and adolescents. This study aimed to complement research from Leipzig 1994-2008 to seek trends within risk factors, treatments, and outcomes throughout the last decade. We retrospectively investigated data of 47 inpatients aged 0-18 admitted to Leipzig University Department of Pediatrics who matched ICD-10 code T75.1 from 2008 to 2020 and compared them to a preceding study at the same institution. We also examined the prognostic value of parameters regarding the patients' outcomes. There were three median incidents per annum. The median age was 2.75 years; 76% of incidents happened in males. An accumulation was seen during the summer months and weekends. Most drowning incidents occurred in private ponds or pools (48.9%). Thirty-nine children were discharged without resulting morbidity, four showed neurological impairment, and three died. Risk factors concerning age, sex, and incident characteristics were confirmed. Special supervision needs still apply to 1-3-year-old male children or children with pre-existing health conditions around private pools and ponds. Hospitalization duration shortened, and morbidity and lethality decreased since the previous study. There was structural improvement in primary care and medical documentation. Parameters suggesting good outcomes include a submersion time < 5 min, GCS > 3 points, spontaneous movement upon admission, remaining pupillary light response, the absence of cardiovascular arrest, body temperature ≥ 32 °C, pH > 7, blood glucose < 15 mmol/L, lactate < 14 mmol/L, base excess ≥ -15 mmol/L, and the absence of ARDS. Clear legislation can contribute to improved private home water safety. Further studies should include a broad in- and outpatient spectrum and standardized incident documentation presupposing Utstein-style reporting. Regular reinvestigation of consistent geographical regions facilitates process evaluations of drowning epidemiology and therapy evolution.

Adverse events related to physical restraint use in intensive care units: A review of the literature.

Physical restraints are widely used and accepted as protective measures during treatment in intensive care unit (ICU). This review of the literature summarizes the adverse events and outcomes associated with physical restraint use, and the risk factors associated with their use during treatment in the ICU. The PubMed, Scopus, and Google Scholar databases were screened using predefined search terms to identify studies pertaining to adverse events and/or outcomes associated with physical restraint use, and the factors associated with their use in adult patients admitted to the ICU. A total of 24 articles (including 6126 patients) that were published between 2006 and 2022 were identified. The described adverse events associated with physical restraint use included skin injuries, subsequent delirium, neurofunctional impairment, and a higher rate of post-traumatic stress disorder. Subsequent delirium was the most frequent adverse event to be reported. No alternative measures to physical restraints were discussed, and only one study reported a standardized protocol for their use. Although physical restraint use has been reported to be associated with adverse events (including neurofunctional impairment) in the literature, the available evidence is limited. Although causality cannot be confirmed, a definite association appears to exist. Our findings suggest that it is essential to improve awareness regarding their adverse impact and optimize approaches for their detection, management, and prevention using protocols or checklists.

Concurrence of seizures and peri-ictal delirium in the critically ill - its frequency, associated characteristics, and outcomes.

BACKGROUND: To assess the frequency, clinical features, and outcome of peri-ictal delirium in adult patients experiencing seizures during intensive care. METHODS: This observational study was conducted at a Swiss intensive care unit from 2015 to 2020. Patients aged ≥ 18 years with seizures were categorized as peri-ictal delirious (Intensive Care Delirium Screening Checklist [i.e., ICDSC] ≥ 4) or not (i.e., ICDSC < 4) within 24 h of seizures. The frequency of peri-ictal delirium and in-hospital death were defined as the primary endpoints. Illness severity and treatment characteristics between delirious and non-delirious patients were secondary endpoints. Logistic regression was used to compare in-hospital death and differences regarding clinical characteristics between delirious and non-delirious patients. RESULTS: 48% of 200 patients had peri-ictal delirium for a median of 3 days. Delirious patients were older (median age 69 vs. 62 years, p = 0.002), had lower Simplified Acute Physiology Scores II (SAPS II; median 43 vs. 54, p = 0.013), received neuroleptics more frequently (31 vs. 5%, p < 0.001), were mechanically ventilated less often (56% vs. 73%, p = 0.013) and shorter (median 3 vs. 5 days, p = 0.011), and had decreased odds for in-hospital death with delirium (OR = 0.41, 95% CI 0.20-0.84) in multivariable analyses. CONCLUSIONS: Delirium emerged in every second patient experiencing seizures and was associated with lower SAPS II, shorter mechanical ventilation, and better outcomes, contradicting assumptions that altered cerebral function, from seizures and delirium, are linked to unfavorable outcomes.

Advance directives in the intensive care unit: An eight-year vanguard cohort study.

PURPOSE: To investigate the frequency, content, and clinical translation of advance directives in intensive care units (ICUs). MATERIAL AND METHODS: Retrospective cohort study in a Swiss tertiary ICU, including patients with advance directives treated in ICUs ≥48 h. The primary endpoint was the violation of directives. Key secondary endpoints were the directives' prevalence and their translation into clinical practice. RESULTS: Of 5'851 patients treated ≥48 h in ICUs, 2.7 % had documented directives. Despite 92 % using templates, subjective or contradictory wording was found in 19 % and 12 %. Nine percent of directives were violated. Patients with directive violations had worse in-hospital outcomes (p = 0.012). At admission, 64 % of patients experiencing violations could not communicate, and directives were missing/unrecognized in 30 %. Mostly, directives were not followed regarding life-prolonging measures (6 %), ICU admission (5 %), and mechanical ventilation (3 %). Kaplan Meier statistics revealed a lower survival rate with directives recognized at admission (p = 0.04) and when treatment was withheld (p < 0.001). CONCLUSIONS: Advance directives are available in a minority of ICU patients and often contain subjective/contradictory wording. Physicians respected directives in 90 % of patients, with treatment adapted following their wishes. However, violation of directives may have serious consequences with unfavorable in-hospital outcomes and decreased long-term survival with treatment adaption following directives.

Addressing climate change with behavioral science: A global intervention tournament in 63 countries.

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions' effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior-several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people's initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.

Simultaneous electroencephalographic and functional magnetic resonance imaging indicate impaired cortical top-down processing in association with anesthetic-induced unconsciousness.

BACKGROUND: In imaging functional connectivity (FC) analyses of the resting brain, alterations of FC during unconsciousness have been reported. These results are in accordance with recent electroencephalographic studies observing impaired top-down processing during anesthesia. In this study, simultaneous records of functional magnetic resonance imaging (fMRI) and electroencephalogram were performed to investigate the causality of neural mechanisms during propofol-induced loss of consciousness by correlating FC in fMRI and directional connectivity (DC) in electroencephalogram. METHODS: Resting-state 63-channel electroencephalogram and blood oxygen level-dependent 3-Tesla fMRI of 15 healthy subjects were simultaneously registered during consciousness and propofol-induced loss of consciousness. To indicate DC, electroencephalographic symbolic transfer entropy was applied as a nonlinear measure of mutual interdependencies between underlying physiological processes. The relationship between FC of resting-state networks of the brain (z values) and DC was analyzed by a partial correlation. RESULTS: Independent component analyses of resting-state fMRI showed decreased FC in frontoparietal default networks during unconsciousness, whereas FC in primary sensory networks increased. DC indicated a decline in frontal-parietal (area under the receiver characteristic curve, 0.92; 95% CI, 0.68-1.00) and frontooccipital (0.82; 0.53-1.00) feedback DC (P<0.05 corrected). The changes of FC in the anterior default network correlated with the changes of DC in frontal-parietal (rpartial=+0.62; P=0.030) and frontal-occipital (+0.63; 0.048) electroencephalographic electrodes (P<0.05 corrected). CONCLUSION: The simultaneous propofol-induced suppression of frontal feedback connectivity in the electroencephalogram and of frontoparietal FC in the fMRI indicates a fundamental role of top-down processing for consciousness.

Neurological evolution of severe baclofen intoxication: from brain death mimic to recovered brain function.

Patients with brain death have by definition irreversible and complete loss of brainstem reflexes. Before a definite diagnosis of brain death can be confirmed, all potential confounders must be thoroughly excluded. Baclofen intoxication is a rare cause of brain death mimic characterised by transient deep coma and absence of brainstem reflexes and might be mistaken with brain death. We report the case of a female patient in her 70s who ingested baclofen with suicidal intent and was admitted with a deep coma and loss of all brainstem reflexes and a spontaneous burst-suppression pattern in the electroencephalography which resolved over 10 hours. After a state mimicking brain death for 6 hours, the patient experienced complete recovery. Severe baclofen intoxication can mimic brain death clinically and is associated with temporary pathological electroencephalographic findings. Awareness of this toxidrome is crucial, as appropriate management can lead to full recovery.

Large but diminishing effects of climate action nudges under rising costs.

Behavioural public policy has received broad research attention, particularly in the domain of motivating pro-environmental behaviours. We investigate how far the efficacy of arguably one the most popular behavioural policy tools (green 'default change' nudges) depends on the associated cost. On the basis of a field study involving carbon offsets for over 30,000 flights booked by more than 11,000 airline customers, we show that green defaults have a large effect on voluntary climate action, even when several hundreds of Euros are at stake. The effect fully vanishes only as costs approach approximately €800.