Paediatric antibiotic prescribing in a nationwide direct-to-consumer telemedicine platform in France, 2018-2021.

Background: Recent regulatory and reimbursement changes facilitated the development of teleconsultation within primary care. French guidance advises against antibiotic prescribing in children in teleconsultation. We assessed paediatric antibiotic prescribing on a French teleconsultation platform. Methods: This cross-sectional observational study analysed paediatric (0-14 years) visits on a national direct-to-consumer teleconsultation platform between January 2018 and December 2021. Teleconsultations with complete information regarding diagnosis (ICD-10 coding) and prescriptions were included. We assessed antibiotic prescription rates per 100 visits across diagnoses and used logistic regression to identify factors associated with antibiotic prescribing. Results: In the 37 587 included paediatric teleconsultations (median age 3 years) performed by 713 general practitioners (GPs) and 89 paediatricians, antibiotics were prescribed for 12.1%. Respiratory tract infections (RTIs) accounted for 49.5% of antibiotic prescriptions. Antibiotic prescription rates per 100 visits were: sinusitis, 69.5%; urinary tract infections, 62.2%; pharyngitis, 59.0%; pneumonia, 45.5%; otitis, 46.6%; bronchitis, 19.6%; rhinitis, 11.6%; bronchiolitis 6.6%. Antibiotic prescription rates were higher in GPs than paediatricians [OR 2.21 (IC95% 2.07-2.35)], among physicians aged 45-54 and over 65 [OR 1.66 (1.48-1.85) and 1.48 (1.32-1.66), respectively], in female practitioners [OR 1.13 (1.05-1.21)], in children 3-6 years old [OR 1.41 (1.28-1.56)] and over 6 [OR 1.50 (1.35-1.66)], during winter [OR 1.28 (1.21-1.37)] and for RTIs [OR 1.99 (1.87-2.10)]. Antibiotic prescription rates were lower in doctors with extensive experience in teleconsultation [OR 0.92 (0.86-0.98)]. Conclusions: Despite current recommendations, paediatric patients were frequently prescribed antibiotics during acute care teleconsultations. Specific antibiotic stewardship campaigns should target paediatric teleconsultations.

Quality Improvement Intervention Using Social Prescribing at Discharge in a University Hospital in France: Quasi-Experimental Study.

BACKGROUND: Social prescription is seen as a public health intervention tool with the potential to mitigate social determinants of health. On one side, social prescription is not yet well developed in France, where social workers usually attend to social needs, and historically, there is a deep divide between the health and social sectors. On the other side, discharge coordination is gaining attention in France as a critical tool to improve the quality of care, assessed indirectly using unplanned rehospitalization rates. OBJECTIVE: This study aims to combine social prescription and discharge coordination to assess the need for social prescription and its effect on unplanned rehospitalization rates. METHODS: We conducted a quasi-experimental study in two departments of medicine in a French university hospital in a disadvantaged suburb of Paris over 2 years (October 2019-October 2021). A discharge coordinator screened patients for social prescribing needs and provided services on the spot or referred the patient to the appropriate service when needed. The primary outcome was the description of the services delivered by the discharge coordinator and of its process, as well as the characteristics of the patients in terms of social needs. The secondary outcome was the comparison of unplanned rehospitalization rates after data chaining. RESULTS: A total of 223 patients were included in the intervention arm, with recruitment being disrupted by the COVID-19 pandemic. More than two-thirds of patients (n=154, 69.1%) needed help understanding discharge information. Slightly less than half of the patients (n=98, 43.9%) seen by the discharge coordinator needed social prescribing, encompassing language, housing, health literacy, and financial issues. The social prescribing covered a large range of services, categorized into finding a general practitioner or private sector nurse, including language-matching; referral to a social worker; referral to nongovernmental organization or group activities; support for transportation issues; support for health-related administrative procedures; and support for additional appointments with nonmedical clinicians. All supports were delivered in a highly personalized way. Ethnic data collection was not legally permitted, but for 81% (n=182) of the patients, French was not the mother tongue. After data chaining, rehospitalization rates were compared between 203 patients who received the intervention (n=5, 3.1%) versus 2095 patients who did not (n=51, 2.6%), and there was no statistical difference. CONCLUSIONS: First, our study revealed the breadth of patient's unmet social needs in our university hospital, which caters to an area where the immigrant population is high. The study also revealed the complexity of the discharge coordinator's work, who provided highly personalized support and managed to gain trust. Hospital discharge could be used in France as an opportunity in disadvantaged settings. Eventually, indicators other than the rehospitalization rate should be devised to evaluate the effect of social prescribing and discharge coordination.

Use of actigraphy for monitoring agitation and rest-activity cycles in patients with acute traumatic brain injury in the ICU.

BACKGROUND: In traumatic brain injury patients (TBI) admitted to the intensive care unit (ICU), agitation can lead to accidental removal of catheters, devices as well as self-extubation and falls. Actigraphy could be a potential tool to continuously monitor agitation. The objectives of this study were to assess the feasibility of monitoring agitation with actigraphs and to compare activity levels in agitated and non-agitated critically ill TBI patients. METHODS: Actigraphs were placed on patients' wrists; 24-hour monitoring was continued until ICU discharge or limitation of therapeutic efforts. Feasibility was assessed by actigraphy recording duration and missing activity count per day. RESULTS: Data from 25 patients were analyzed. The mean number of completed day of actigraphy per patient was 6.5 ± 5.1. The mean missing activity count was 20.3 minutes (±81.7) per day. The mean level of activity measured by raw actigraphy counts per minute over 24 hours was higher in participants with agitation than without agitation. CONCLUSIONS: This study supports the feasibility of actigraphy use in TBI patients in the ICU. In the acute phase of TBI, agitated patients have higher levels of activity, confirming the potential of actigraphy to monitor agitation.

Longer sleep duration and neuroinflammation in at-risk elderly with a parental history of Alzheimer's disease.

STUDY OBJECTIVES: Although short sleep could promote neurodegeneration, long sleep may be a marker of ongoing neurodegeneration, potentially as a result of neuroinflammation. The objective was to evaluate sleep patterns with age of expected Alzheimer's disease (AD) onset and neuroinflammation. METHODS: We tested 203 dementia-free participants (68.5 ±â€…5.4 years old, 78M). The PREVENT-AD cohort includes older persons with a parental history of AD whose age was nearing their expected AD onset. We estimated expected years to AD onset by subtracting the participants' age from their parent's at AD dementia onset. We extracted actigraphy sleep variables of interest (times of sleep onset and morning awakening, time in bed, sleep efficiency, and sleep duration) and general profiles (sleep fragmentation, phase delay, and hypersomnia). Cerebrospinal fluid (CSF) inflammatory biomarkers were assessed with OLINK multiplex technology. RESULTS: Proximity to, or exceeding, expected age of onset was associated with a sleep profile suggestive of hypersomnia (longer sleep and later morning awakening time). This hypersomnia sleep profile was associated with higher CSF neuroinflammatory biomarkers (IL-6, MCP-1, and global score). Interaction analyses revealed that some of these sleep-neuroinflammation associations were present mostly in those closer/exceeding the age of expected AD onset, APOE4 carriers, and those with better memory performance. CONCLUSIONS: Proximity to, or exceeding, parental AD dementia onset was associated with a longer sleep pattern, which was related to elevated proinflammatory CSF biomarkers. We speculate that longer sleep may serve a compensatory purpose potentially triggered by neuroinflammation as individuals are approaching AD onset. Further studies should investigate whether neuroinflammatory-triggered long sleep duration could mitigate cognitive deficits.

Day-to-day sleep variability with Alzheimer's biomarkers in at-risk elderly.

INTRODUCTION: Measuring day-to-day sleep variability might reveal unstable sleep-wake cycles reflecting neurodegenerative processes. We evaluated the association between Alzheimer's disease (AD) fluid biomarkers with day-to-day sleep variability. METHODS: In the PREVENT-AD cohort, 203 dementia-free participants (age: 68.3 ± 5.4; 78 males) with a parental history of sporadic AD were tested with actigraphy and fluid biomarkers. Day-to-day variability (standard deviations over a week) was assessed for sleep midpoint, duration, efficiency, and nighttime activity count. RESULTS: Lower cerebrospinal fluid (CSF) ApoE, higher CSF p-tau181/amyloid-ß (Aß)42, and higher plasma p-tau231/Aß42 were associated with higher variability of sleep midpoint, sleep duration, and/or activity count. The associations between fluid biomarkers with greater sleep duration variability were especially observed in those that carried the APOE4 allele, mild cognitive impairment converters, or those with gray matter atrophy. DISCUSSION: Day-to-day sleep variability were associated with biomarkers of AD in at-risk individuals, suggesting that unstable sleep promotes neurodegeneration or, conversely, that AD neuropathology disrupts sleep-wake cycles.

Depth of Anesthesia and Nociception Monitoring: Current State and Vision For 2050.

Anesthesia objectives have evolved into combining hypnosis, amnesia, analgesia, paralysis, and suppression of the sympathetic autonomic nervous system. Technological improvements have led to new monitoring strategies, aimed at translating a qualitative physiological state into quantitative metrics, but the optimal strategies for depth of anesthesia (DoA) and analgesia monitoring continue to stimulate debate. Historically, DoA monitoring used patient's movement as a surrogate of awareness. Pharmacokinetic models and metrics, including minimum alveolar concentration for inhaled anesthetics and target-controlled infusion models for intravenous anesthesia, provided further insights to clinicians, but electroencephalography and its derivatives (processed EEG; pEEG) offer the potential for personalization of anesthesia care. Current studies appear to affirm that pEEG monitoring decreases the quantity of anesthetics administered, diminishes postanesthesia care unit duration, and may reduce the occurrence of postoperative delirium (notwithstanding the difficulties of defining this condition). Major trials are underway to further elucidate the impact on postoperative cognitive dysfunction. In this manuscript, we discuss the Bispectral (BIS) index, Narcotrend monitor, Patient State Index, entropy-based monitoring, and Neurosense monitor, as well as middle latency evoked auditory potential, before exploring how these technologies could evolve in the upcoming years. In contrast to developments in pEEG monitors, nociception monitors remain by comparison underdeveloped and underutilized. Just as with anesthetic agents, excessive analgesia can lead to harmful side effects, whereas inadequate analgesia is associated with increased stress response, poorer hemodynamic conditions and coagulation, metabolic, and immune system dysregulation. Broadly, 3 distinct monitoring strategies have emerged: motor reflex, central nervous system, and autonomic nervous system monitoring. Generally, nociceptive monitors outperform basic clinical vital sign monitoring in reducing perioperative opioid use. This manuscript describes pupillometry, surgical pleth index, analgesia nociception index, and nociception level index, and suggest how future developments could impact their use. The final section of this review explores the profound implications of future monitoring technologies on anesthesiology practice and envisages 3 transformative scenarios: helping in creation of an optimal analgesic drug, the advent of bidirectional neuron-microelectronic interfaces, and the synergistic combination of hypnosis and virtual reality.

Theoretical Neurobiology of Consciousness Applied to Human Cerebral Organoids.

Organoids and specifically human cerebral organoids (HCOs) are one of the most relevant novelties in the field of biomedical research. Grown either from embryonic or induced pluripotent stem cells, HCOs can be used as in vitro three-dimensional models, mimicking the developmental process and organization of the developing human brain. Based on that, and despite their current limitations, it cannot be assumed that they will never at any stage of development manifest some rudimentary form of consciousness. In the absence of behavioral indicators of consciousness, the theoretical neurobiology of consciousness being applied to unresponsive brain-injured patients can be considered with respect to HCOs. In clinical neurology, it is difficult to discern a capacity for consciousness in unresponsive brain-injured patients who provide no behavioral indicators of consciousness. In such scenarios, a validated neurobiological theory of consciousness, which tells us what the neural mechanisms of consciousness are, could be used to identify a capacity for consciousness. Like the unresponsive patients that provide a diagnostic difficulty for neurologists, HCOs provide no behavioral indicators of consciousness. Therefore, this article discusses how three prominent neurobiological theories of consciousness apply to human cerebral organoids. From the perspective of the Temporal Circuit Hypothesis, the Global Neuronal Workspace Theory, and the Integrated Information Theory, we discuss what neuronal structures and functions might indicate that cerebral organoids have a neurobiological capacity to be conscious.

Automated ICD10-Coding of Teleconsultations Conclusions in Primary Care.

The national teleconsultation platform Qare offers a promising tool to collect data in primary care by sharing the same EHR among teleconsultants. Conclusions for every teleconsultation are thus collected by a text using an ICD10 code or not. Nevertheless, the use of the ICD10 classification by primary care doctors is scarce. We developed an algorithm based on bags of words that associates an ICD10 code for each textual conclusion and evaluated it. It shows good performances (88 to 89% concordance) to assign ICD10 category. It could be used to enhance the volume of coded teleconsultations ready to be reused.

Sleep Disruptions in Hospitalized Adults Sustaining a Traumatic Brain Injury: A Scoping Review.

OBJECTIVE: Adults sustaining a traumatic brain injury (TBI) are at risk of sleep disturbances during their recovery, including when such an injury requires hospitalization. However, the sleep-wake profile, and internal and external factors that may interfere with sleep initiation/maintenance in hospitalized TBI patients are poorly understood. This review aimed to: (1) identify/summarize the existing evidence regarding sleep and sleep measurements in TBI adults receiving around-the-clock care in a hospital or during inpatient rehabilitation, and (2) identify internal/external factors linked to poor sleep in this context. METHODS: A scoping review was conducted in accordance with the PRISMA Scoping Review Extension guidelines. A search was conducted in MEDLINE, PsycINFO, CINAHL, and Web of Science databases. RESULTS: Thirty relevant studies were identified. The most common sleep variables that were put forth in the studies to characterize sleep during hospitalization were nighttime sleep time (mean = 6.5 hours; range: 5.2-8.9 hours), wake after sleep onset (87.1 minutes; range: 30.4-180 minutes), and sleep efficiency (mean = 72.9%; range: 33%-96%) using mainly actigraphy, polysomnography, and questionnaires (eg, the sleep-wake disturbance item of the Delirium Rating Scale or the Pittsburgh Sleep Quality Index). Twenty-four studies (80%) suggested that hospitalized TBI patients do not get sufficient nighttime sleep, based on the general recommendations for adults (7-9 hours per night). Sleep disruptions during hospitalization were found to be associated to several internal factors including TBI severity, cognitive status, and analgesia intake. External and modifiable factors, such as noise, light, and patient care, were consistently associated with sleep disruptions in this context. CONCLUSION: Although the literature on sleep disturbances in hospitalized TBI patients has been increasing in recent years, many gaps in knowledge remain, including phenotypes and risk factors. Identifying these factors could help clinicians better understand the multiple sources of TBI patients' sleep difficulties and intervene accordingly.

A scoping review for building a criticality-based conceptual framework of altered states of consciousness.

The healthy conscious brain is thought to operate near a critical state, reflecting optimal information processing and high susceptibility to external stimuli. Conversely, deviations from the critical state are hypothesized to give rise to altered states of consciousness (ASC). Measures of criticality could therefore be an effective way of establishing the conscious state of an individual. Furthermore, characterizing the direction of a deviation from criticality may enable the development of treatment strategies for pathological ASC. The aim of this scoping review is to assess the current evidence supporting the criticality hypothesis, and the use of criticality as a conceptual framework for ASC. Using the PRISMA guidelines, Web of Science and PubMed were searched from inception to February 7th 2022 to find articles relating to measures of criticality across ASC. N = 427 independent papers were initially found on the subject. N = 378 were excluded because they were either: not related to criticality; not related to consciousness; not presenting results from a primary study; presenting model data. N = 49 independent papers were included in the present research, separated in 7 sub-categories of ASC: disorders of consciousness (DOC) (n = 5); sleep (n = 13); anesthesia (n = 18); epilepsy (n = 12); psychedelics and shamanic state of consciousness (n = 4); delirium (n = 1); meditative state (n = 2). Each category included articles suggesting a deviation of the critical state. While most studies were only able to identify a deviation from criticality without being certain of its direction, the preliminary consensus arising from the literature is that non-rapid eye movement (NREM) sleep reflects a subcritical state, epileptic seizures reflect a supercritical state, and psychedelics are closer to the critical state than normal consciousness. This scoping review suggests that, though the literature is limited and methodologically inhomogeneous, ASC are characterized by a deviation from criticality, though its direction is not clearly reported in a majority of studies. Criticality could become, with more extensive research, an effective and objective way to characterize ASC, and help identify therapeutic avenues to improve criticality in pathological brain states. Furthermore, we suggest how anesthesia and psychedelics could potentially be used as neuromodulation techniques to restore criticality in DOC.

Refinement of the Target Population for Colorectal Cancer Screening in France, Inventory as a Prelude to the Use of Medico-Administrative Database.

The study describes the level of improvement in the risk of misclassification that would be achieved by refining the campaign target population using a query in the French medico-administrative database (SNDS). The SNDS's use requires other new strategies that can minimize the number of people wrongly included in the campaigns, because its accuracy is less than 100%.

Aperiodic brain activity and response to anesthesia vary in disorders of consciousness.

In the human electroencephalogram (EEG), oscillatory power co-exist with non-oscillatory, aperiodic activity. Although EEG analysis has traditionally focused exclusively on oscillatory power, recent investigations have shown that the aperiodic EEG component can distinguish conscious wakefulness from sleep and anesthetic-induced unconsciousness. This study investigates the aperiodic EEG component of individuals in a disorder of consciousness (DOC); how it changes in response to exposure to anesthesia; and how it relates to the brain's information richness and criticality. High-density EEG was recorded from 43 individuals in a DOC, with 16 of these individuals undergoing a protocol of propofol anesthesia. The aperiodic component was defined by the spectral slope of the power spectral density. Our results demonstrate that the EEG aperiodic component is more informative about the participants' level of consciousness than the oscillatory component, especially for patients that suffered from a stroke. Importantly, the pharmacologically induced change in the spectral slope from 30 to 45 Hz positively correlated with individual's pre-anesthetic level of consciousness. The pharmacologically induced loss of information-richness and criticality was associated with individual's pre-anesthetic aperiodic component. During exposure to anesthesia, the aperiodic component distinguished individuals with DOC, according to their 3-month recovery status. The aperiodic EEG component has been historically neglected; this research highlights the necessity of considering this measure for the assessment of individuals in DOC and future research that seeks to understand the neurophysiological underpinnings of consciousness.

Assessing Cognitive Outcomes in Coma Survivors: A Literature Review.

(1) Background: Although cognitive impairments in coma survivors are common, methods of measuring long-term cognitive outcomes in this population are inconsistent, precluding the development of a strong evidence-base to support clinical decision making. In this literature review, we identify and characterize the measures used to track cognitive recovery in coma survivors to data. (2) Methods: We extracted the instrument used for cognitive assessment, the cognitive domains assessed, methods administration and scoring, and timing of assessment from 134 of 996 screened records. (3) Results: A total of 133 unique cognitive tests and cognitive testing batteries were identified, with 97 cognitive instruments used in less than three articles. The instruments assessed 20 different cognitive domains, with 73 articles also using tests that assess general "cognitive ability". Cognitive instruments ranged from subjective assessments to comprehensive cognitive batteries. There were inconsistent points of reference for the timing of assessment across studies, with few studies repeating assessments at more than one time point, and arbitrary time intervals between tests. (4) Conclusions: Overall, this review illustrates the enormous disparity between studies that track cognitive outcome in coma survivors, and the need for a systematic, patient-accessible method of assessing cognitive functioning in future studies with this population.

Users' Reactions to Announced Vaccines Against COVID-19 Before Marketing in France: Analysis of Twitter Posts.

BACKGROUND: Within a few months, the COVID-19 pandemic had spread to many countries and had been a real challenge for health systems all around the world. This unprecedented crisis has led to a surge of online discussions about potential cures for the disease. Among them, vaccines have been at the heart of the debates and have faced lack of confidence before marketing in France. OBJECTIVE: This study aims to identify and investigate the opinions of French Twitter users on the announced vaccines against COVID-19 through sentiment analysis. METHODS: This study was conducted in 2 phases. First, we filtered a collection of tweets related to COVID-19 available on Twitter from February 2020 to August 2020 with a set of keywords associated with vaccine mistrust using word embeddings. Second, we performed sentiment analysis using deep learning to identify the characteristics of vaccine mistrust. The model was trained on a hand-labeled subset of 4548 tweets. RESULTS: A set of 69 relevant keywords were identified as the semantic concept of the word "vaccin" (vaccine in French) and focused mainly on conspiracies, pharmaceutical companies, and alternative treatments. Those keywords enabled us to extract nearly 350,000 tweets in French. The sentiment analysis model achieved 0.75 accuracy. The model then predicted 16% of positive tweets, 41% of negative tweets, and 43% of neutral tweets. This allowed us to explore the semantic concepts of positive and negative tweets and to plot the trends of each sentiment. The main negative rhetoric identified from users' tweets was that vaccines are perceived as having a political purpose and that COVID-19 is a commercial argument for the pharmaceutical companies. CONCLUSIONS: Twitter might be a useful tool to investigate the arguments for vaccine mistrust because it unveils political criticism contrasting with the usual concerns on adverse drug reactions. As the opposition rhetoric is more consistent and more widely spread than the positive rhetoric, we believe that this research provides effective tools to help health authorities better characterize the risk of vaccine mistrust.

Paradoxical markers of conscious levels: Effects of propofol on patients in disorders of consciousness.

Human consciousness is widely understood to be underpinned by rich and diverse functional networks, whose breakdown results in unconsciousness. Candidate neural correlates of anesthetic-induced unconsciousness include: (1) disrupted frontoparietal functional connectivity; (2) disrupted brain network hubs; and (3) reduced spatiotemporal complexity. However, emerging counterexamples have revealed that these markers may appear outside of the state they are associated with, challenging both their inclusion as markers of conscious level, and the theories of consciousness that rely on their evidence. In this study, we present a case series of three individuals in disorders of consciousness (DOC) who exhibit paradoxical brain responses to exposure to anesthesia. High-density electroencephalographic data were recorded from three patients with unresponsive wakefulness syndrome (UWS) while they underwent a protocol of propofol anesthesia with a targeted effect site concentration of 2 µg/ml. Network hubs and directionality of functional connectivity in the alpha frequency band (8-13 Hz), were estimated using the weighted phase lag index (wPLI) and directed phase lag index (dPLI). The spatiotemporal signal complexity was estimated using three types of Lempel-Ziv complexity (LZC). Our results illustrate that exposure to propofol anesthesia can paradoxically result in: (1) increased frontoparietal feedback-dominant connectivity; (2) posterior network hubs; and (3) increased spatiotemporal complexity. The case examples presented in this paper challenge the role of functional connectivity and spatiotemporal complexity in theories of consciousness and for the clinical evaluation of levels of human consciousness.

Qualitative Evaluation of a Drug Terminology Server.

BACKGROUND: Although the drug is finished, identifiable, there is no universally accepted standard for naming them. The objective of this work is to evaluate qualitatively the HeTOP drug terminology server by two categories of students: (a) pharmacy students and (b) a control group. METHODS: A formal evaluation was built to measure the perception of users about the HeTOP drug server, using the three mains questions about "teaching interest", "skill interest" (or competence) and "ergonomics". RESULTS: The three pharmacy student subgroups gave the best and the worst score to the same categories. CONCLUSION: All three criteria are rated above 6.5 out of 10. The HeTOP drug terminology server is freely available to "non drug" specialists (URL: www.hetop.eu/hetop/drugs/).

When Context Matters for Credible Measurement of Drug-Drug Interactions Based on Real-World Data.

The frequency of potential drug-drug interactions (DDI) in published studies on real world data considerably varies due to the methodological framework. Contextualization of DDI has a proven effect in limiting false positives. In this paper, we experimented with the application of various DDIs contexts elements to see their impact on the frequency of potential DDIs measured on the same set of prescription data collected in EDSaN, the clinical data warehouse of Rouen University Hospital. Depending on the context applied, the frequency of daily prescriptions with potential DDI ranged from 0.89% to 3.90%. Substance-level analysis accounted for 48% of false positives because it did not account for some drug-related attributes. Consideration of the patient's context could eliminate up to an additional 29% of false positives.

Reliability of Drug-Drug Interaction Measurement on Real-Word Data: The ReMIAMes Project.

The ReMIAMes project proposes a methodological framework to provide a reliable and reproducible measurement of the frequency of drug-drug interactions (DDI) when performed on real-world data. This framework relies on (i) a fine-grained and contextualized definition of DDIs, (ii) a shared minimum information model to select the appropriate data for the correct interpretation of potential DDIs, (iii) an ontology-based inference module able to handle missing data to classify prescription lines with potential DDIs, (iv) a report generator giving the value of the measurement and explanations when potential false positive are detected due to a lack of available data. All the tools developed are intended to be publicly shared under open license.

Sleep from acute to chronic traumatic brain injury and cognitive outcomes.

STUDY OBJECTIVES: Traumatic brain injuries (TBIs) cause persistent cerebral damage and cognitive deficits. Because sleep may be a critical factor for brain recovery, we characterized the sleep of patients with TBI from early hospitalization to years post-injury and explored the hypothesis that better sleep during hospitalization predicts more favorable long-term cognitive outcomes. METHODS: We tested patients with moderate-to-severe TBI in the hospitalized (n = 11) and chronic (n = 43) stages using full-night polysomnography, with 82% of the hospitalized group being retested years post-injury. Hospitalized patients with severe orthopedic and/or spinal cord injury (n = 14) and healthy participants (n = 36) were tested as controls for the hospitalized and chronic TBI groups, respectively. Groups had similar age and sex and were compared for sleep characteristics, including slow waves and spindles. For patients with TBI, associations between sleep during hospitalization and long-term memory and executive function were assessed. RESULTS: Hospitalized patients with TBI or orthopedic injuries had lower sleep efficiency, higher wake after sleep onset, and lower spindle density than the chronic TBI and healthy control groups, but only hospitalized patients with brain injury had an increased proportion of slow-wave sleep. During hospitalization for TBI, less fragmented sleep, more slow-wave sleep, and higher spindle density were associated to more favorable cognitive outcomes years post-injury, while injury severity markers were not associated with these outcomes. CONCLUSION: These findings highlight the importance of sleep following TBI, as it could be a strong predictor of neurological recovery, either as a promoter or an early marker of cognitive outcomes.

Brain Responses to Propofol in Advance of Recovery from Coma and Disorders of Consciousness: A Preliminary Study.

Rationale: Predicting recovery of consciousness in unresponsive, brain-injured individuals has crucial implications for clinical decision-making. Propofol induces distinctive brain network reconfiguration in the healthy brain as it loses consciousness. In patients with disorders of consciousness, the brain network's reconfiguration to propofol may reveal the patient's underlying capacity for consciousness. Objectives: To design and test a new metric for the prognostication of consciousness recovery in disorders of consciousness. Methods: Using a within-subject design, we conducted an anesthetic protocol with concomitant high-density EEG in 12 patients with a disorder of consciousness after a brain injury. We quantified the reconfiguration of EEG network hubs and directed functional connectivity before, during, and after propofol exposure and obtained an index of propofol-induced network reconfiguration: the adaptive reconfiguration index. We compared the index of patients who recovered consciousness 3 months after EEG (n = 3) to that of patients who did not recover or remained in a chronic disorder of consciousness (n = 7) and conducted a logistic regression to assess prognostic accuracy. Measurements and Main Results: The adaptive reconfiguration index was significantly higher in patients who later recovered full consciousness (U value = 21, P = 0.008) and able to discriminate with 100% accuracy whether the patient recovered consciousness. Conclusions: The adaptive reconfiguration index of patients who recovered from a disorder of consciousness at 3-month follow-up was linearly separable from that of patients who did not recover or remained in a chronic disorder of consciousness on the single-subject level. EEG and propofol can be administered at the bedside with few contraindications, affording the adaptive reconfiguration index tremendous translational potential as a prognostic measure of consciousness recovery in acute clinical settings.