Adverse Effects After Prehospital Administration of Naloxone by Bystanders: A Preliminary Study.

OBJECTIVE: Opioid use disorder is a cause of significant morbidity and mortality. In order to reverse opioid overdose as quickly as possible, many institutions and municipalities have encouraged people with no professional medical training to carry and administer naloxone. This study sought to provide preliminary data for research into the rates of adverse effects of naloxone when administered by bystanders compared to Emergency Medical Services (EMS) personnel, since this question has not been studied previously. METHODS: This was a retrospective cohort study performed at an urban, tertiary, academic medical center that operates its own EMS service. A consecutive sample of patients presenting to EMS with opioid overdose requiring naloxone was separated into two groups based on whether naloxone was administered by bystanders or by EMS personnel. Each group was analyzed to determine the incidence of four pre-specified adverse events. RESULTS: There was no significant difference in the rate of adverse events between the bystander (19%) and EMS (16%) groups (OR = 1.23; 95% CI, 0.63 - 2.32; P = .499) in this small sample. Based on these initial results, a study would need a sample size of 6,188 in order to reach this conclusion with 80% power. Similarly, there were no significant differences in the rates of any of the individual adverse events. Secondary analysis of patients' demographics showed differences between the two groups which generate hypotheses for further investigation of disparities in naloxone administration. CONCLUSIONS: This preliminary study provides foundational data for further investigation of naloxone administration by bystanders. Adverse events after the prehospital administration of naloxone are rare, and future studies will require large sample sizes. These preliminary data did not demonstrate a statistically significant difference in adverse event rates when comparing naloxone administration by bystanders and EMS clinicians. This study provides data that will be useful for conducting further research on multiple facets of this topic.

Oscillatory Responses to Tactile Stimuli of Different Intensity.

Tactile perception encompasses several submodalities that are realized with distinct sensory subsystems. The processing of those submodalities and their interactions remains understudied. We developed a paradigm consisting of three types of touch tuned in terms of their force and velocity for different submodalities: discriminative touch (haptics), affective touch (C-tactile touch), and knismesis (alerting tickle). Touch was delivered with a high-precision robotic rotary touch stimulation device. A total of 39 healthy individuals participated in the study. EEG cluster analysis revealed a decrease in alpha and beta range (mu-rhythm) as well as theta and delta increase most pronounced to the most salient and fastest type of stimulation. The participants confirmed that slower stimuli targeted to affective touch low-threshold receptors were the most pleasant ones, and less intense stimuli aimed at knismesis were indeed the most ticklish ones, but those sensations did not form an EEG cluster, probably implying their processing involves deeper brain structures that are less accessible with EEG.

Studying perceptual bias in favor of the from-above Necker cube perspective in a goal-directed behavior.

When viewing a completely ambiguous image, different interpretations can switch involuntarily due to internal top-down processing. In the case of the Necker cube, an entirely ambiguous stimulus, observers often display a bias in perceptual switching between two interpretations based on their perspectives: one with a from-above perspective (FA) and the other with a from-below perspective (FB). Typically, observers exhibit a priori top-down bias in favor of the FA interpretation, which may stem from a statistical tendency in everyday life where we more frequently observe objects from above. However, it remains unclear whether this perceptual bias persists when individuals voluntarily decide on the Necker cube's interpretation in goal-directed behavior, and the impact of ambiguity in this context is not well-understood. In our study, we instructed observers to voluntarily identify the orientation of a Necker cube while manipulating its ambiguity from low (LA) to high (HA). Our investigation aimed to test two hypotheses: (i) whether the perspective (FA or FB) would result in a bias in response time, and (ii) whether this bias would depend on the level of stimulus ambiguity. Additionally, we analyzed electroencephalogram (EEG) signals to identify potential biomarkers that could explain the observed perceptual bias. The behavioral results confirmed a perceptual bias in favor of the from-above perspective, as indicated by shorter response times. However, this bias diminished for stimuli with high ambiguity. For the LA stimuli, the occipital theta-band power consistently exceeded the frontal theta-band power throughout most of the decision-making time. In contrast, for the HA stimuli, the frontal theta-band power started to exceed the occipital theta-band power during the 0.3-s period preceding the decision. We propose that occipital theta-band power reflects evidence accumulation, while frontal theta-band power reflects its evaluation and decision-making processes. For the FB perspective, occipital theta-band power exhibited higher values and dominated over a longer duration, leading to an overall increase in response time. These results suggest that more information and more time are needed to encode stimuli with a FB perspective, as this template is less common for the observers compared to the template for a cube with a FA perspective.

A Shorter Door-In-Door-Out Time Is Associated with Improved Outcome in Large Vessel Occlusion Stroke.

Introduction: Endovascular thrombectomy (EVT) significantly improves outcomes in large vessel occlusion stroke (LVOS). When a patient with a LVOS arrives at a hospital that does not perform EVT, emergent transfer to an endovascular stroke center (ESC) is required. Our objective was to determine the association between door-in-door-out time (DIDO) and 90-day outcomes in patients undergoing EVT. Methods: We conducted an analysis of the Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry of 2,400 LVOS patients treated at nine ESCs in the United States. We examined the association between DIDO times and 90-day outcomes as measured by the modified Rankin scale. Results: A total of 435 patients were included in the final analysis. The mean DIDO time for patients with good outcomes was 17 minute shorter than patients with poor outcomes (122 minutes [min] vs 139 min, P = 0.04). Absolute DIDO cutoff times of ≤60 min, ≤90 min, or ≤120 min were not associated with improved functional outcomes (46.4 vs 32.3%, P = 0.12; 38.6 vs 30.6%, P = 0.10; and 36.4 vs 28.9%, P = 0.10, respectively). This held true for patients with hyperacute strokes of less than four-hour onset. Lower baseline National Institutes of Health Stroke Scale (NIHSS) score (11.9 vs 18.2, P = <.001) and younger age (62.5 vs 74.9 years (P < .001) were associated with improved outcomes. On multiple regression analysis, age (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.45-2.02) and baseline NIHSS score (OR 1.67, 95% CI 1.42-1.98) were associated with improved outcomes while DIDO time was not associated with better outcome (OR 1.13, 95% CI 0.99-1.30). Conclusion: Although the DIDO time was shorter for patients with a good outcome, this was non-significant in multiple regression analysis. Receipt of intravenous thrombolysis and time to EVT were not associated with better outcomes, while male gender, lower age, arrival by private vehicle, and lower NIHSS score portended better outcomes. No absolute DIDO-time cutoff or modifiable factor was associated with improved outcomes for LVOS. This study underscores the need to streamline DIDO times but not to set an artificial DIDO time benchmark to meet.

Delay in hospital presentation is the main reason large vessel occlusion stroke patients do not receive intravenous thrombolysi.

Objectives: Intravenous thrombolysis (IVT) and endovascular therapy (EVT) are the mainstays of treatment for large vessel occlusion stroke (LVOS). Prior studies have examined why patients have not received IVT, the most cited reasons being last-known-well (LKW) to hospital arrival of >4.5 hours and minor/resolving stroke symptoms. Given that LVOS patients typically present moderate-to-severe neurologic deficits, these patients should be easier to identify and treat than patients with minor strokes. This investigation explores why IVT was not administered to a cohort of LVOS patients who underwent EVT. Methods: This is an analysis of the Optimizing the Use of Prehospital Stroke Systems of Care (OPUS-REACH) registry, which contains patients from 9 endovascular centers who underwent EVT between 2015 and 2020. The exposure of interest was the receipt of intravenous thrombolysis. Descriptive summary statistics are presented as means and SDs for continuous variables and as frequencies with percentages for categorical variables. Two-sample t tests were used to compare continuous variables and the chi-square test was used to compare categorical variables between those who received IVT and those who did not receive EVT. Results: Two thousand forty-three patients were included and 60% did not receive IVT. The most common reason for withholding IVT was LKW to arrival of >4.5 (57.2%). The second most common contraindication was oral anticoagulation (15.5%). On multivariable analysis, 2 factors were associated with not receiving IVT: increasing age (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.78-0.93) and increasing time from LKW-to hospital arrival (OR 0.45 95% CI 0.46-0.49). Conclusion: Like prior studies, the most frequent reason for exclusion from IVT was a LKW to hospital presentation of >4.5 hours; the second reason was anticoagulation. Efforts must be made to increase awareness of the time-sensitive nature of IVT and evaluate the safety of IVT in patients on oral anticoagulants.

Abnormal spectral and scale-free properties of resting-state EEG in girls with Rett syndrome.

Spontaneous EEG contains important information about neuronal network properties that is valuable for understanding different neurological and psychiatric conditions. Rett syndrome (RTT) is a rare neurodevelopmental disorder, caused by mutation in the MECP2 gene. RTT is characterized by severe motor impairments that prevent adequate assessment of cognitive functions. Here we probe EEG parameters obtained in no visual input condition from a 28-channels system in 23 patients with Rett Syndrome and 38 their typically developing peers aged 3-17 years old. Confirming previous results, RTT showed a fronto-central theta power (4-6.25 Hz) increase that correlates with a progression of the disease. Alpha power (6.75-11.75 Hz) across multiple regions was, on the contrary, decreased in RTT, also corresponding to general background slowing reported previously. Among novel results we found an increase in gamma power (31-39.5 Hz) across frontal, central and temporal electrodes, suggesting elevated excitation/inhibition ratio. Long-range temporal correlation measured by detrended fluctuation analysis within 6-13 Hz was also increased, pointing to a more predictable oscillation pattern in RTT. Overall measured EEG parameters allow to differentiate groups with high accuracy, ROC AUC value of 0.92 ± 0.08, indicating clinical relevance.

Factors associated with door-in-door-out times in large vessel occlusion stroke patients undergoing endovascular therapy.

INTRODUCTION: In the management of large vessel occlusion stroke (LVOS), patients are frequently evaluated first at a non-endovascular stroke center and later transferred to an endovascular stroke center (ESC) for endovascular treatment (EVT). The door-in-door-out time (DIDO) is frequently used as a benchmark for transferring hospitals though there is no universally accepted nor evidenced-based DIDO time. The goal of this study was to identify factors affecting DIDO times in LVOS patients who ultimately underwent EVT. METHODS: The Optimizing Prehospital Use of Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry is comprised of all LVOS patients who underwent EVT at one of nine endovascular centers in the Northeast United States between 2015 and 2020. We queried the registry for all patients who were transferred from a non-ESC to one of the nine ESCs for EVT. Univariate analysis was performed using t-tests to obtain a p value. A priori, we defined a p value of <0.05 as significant. Multiple logistic regression was conducted to determine the association of variables to estimate an odds ratio. RESULTS: 511 patients were included in the final analysis. The mean DIDO times for all patients was 137.8 min. Vascular imaging and treatment at a non-certified stroke center were associated with longer DIDO times by 23 and 14 min, respectively. On multivariate analyses, the acquisition of vascular imaging was associated with 16 additional minutes spent at the non-ESC while presentation to a non-stroke certified hospital was associated with 20 additional minutes spent at the transferring hospital. The administration of intravenous thrombolysis (IVT) was associated with 15 min less spent at the non-ESC. DISCUSSION: Vascular imaging and non-stroke certified stroke centers were associated with longer DIDO times. Non-ESCs should integrate vascular imaging into their workflow as feasible to reduce DIDO times. Further work examining other details regarding the transfer process such as transfer via ground or air, could help further identify opportunities to improve DIDO times.

Evolution of endovascular stroke centers and disparities in access to stroke care in four Northeastern states: 2015-2019.

OBJECTIVES: Disparities exist throughout our healthcare system, especially related to access to care. Advanced stroke care for strokes is only available at selected endovascular centers (ESCs) in the United States. Although the number of ESCs increase each year, this does not necessarily reflect increased access to care. Here, we look at the evolution of ESC in four states and disparities in access to advanced stroke care. MATERIALS AND METHODS: This is a descriptive study of access to ESCs in four Northeastern states between 2015-2019. Using data from the United States Census Bureau and spatial analysis, we examined the proportion of the population with drive times of less than 60 minutes stratified by income, race/ethnicity, population density, and insurance. We also calculated the mean drive time for each of these socioeconomic groups from their census tracts to the nearest ESC. RESULTS: Between 2015 and 2019, the number of ESCs increased from 15 to 48. The proportion of patients within a 60-minute drive of an ESC increased from 77% to 88%. However, only 66% of the least densely populated quartile lived within 60 min of an ESC. By income, access to ESCs in the wealthiest quartile was 96.6% compared to 83.7% in the lowest quartile. Hispanics and non-Hispanic Blacks had the largest proportions of populations within 60 minutes of an ESC while Non-Hispanic Whites had the smallest. CONCLUSIONS: This study underscores the need to evaluate the placement of new ESCs to assure that these hospitals decrease disparities and increase access to advanced stroke care.

Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH): a pragmatic registry of large vessel occlusion stroke patients to create evidence-based stroke systems of care and eliminate disparities in access to stroke care.

BACKGROUND: Large vessel occlusion (LVO) strokes are best treated with rapid endovascular therapy (EVT). There are two routes that LVO stroke patients can take to EVT therapy when transported by EMS: primary transport (ambulance transports directly to an endovascular stroke center (ESC) or secondary transport (EMS transports to a non-ESC then transfers for EVT). There is no clear evidence which path to care results in better functional outcomes for LVO stroke patients. To find this answer, an analysis of a large, real-world population of LVO stroke patients must be performed. METHODS: A pragmatic registry of LVO stroke patients from nine health systems across the United States. The nine health systems span urban and rural populations as well as the spectrum of socioeconomic statuses. We will use univariate and multivariate analysis to explore the relationships between type of EMS transport, socioeconomic factors, and LVO stroke outcomes. We will use geographic information systems and spatial analysis to examine the complex movements of patients in time and space. To detect an 8% difference between groups, with a 3:1 patient ratio of primary to secondary transports, 95% confidence and 80% power, we will need approximately 1600 patients. The primary outcome is the patients with modified Rankin Scale (mRS) ≤ 2 at 90 days. Subgroup analyses include patients who receive intravenous thrombolysis and duration of stroke systems. Secondary analyses include socioeconomic factors associated with poor outcomes after LVO stroke. DISCUSSION: Using the data obtained from the OPUS-REACH registry, we will develop evidence based algorithms for prehospital transport of LVO stroke patients. Unlike prior research, the OPUS-REACH registry contains patient-level data spanning from EMS dispatch to ninety day functional outcomes. We expect that we will find modifiable factors and socioeconomic disparities associated with poor outcomes in LVO stroke. OPUS-REACH with its breadth of locations, detailed patient records, and multidisciplinary researchers will design the optimal prehospital stroke system of care for LVO stroke patients.

Combining Statistical Analysis and Machine Learning for EEG Scalp Topograms Classification.

Incorporating brain-computer interfaces (BCIs) into daily life requires reducing the reliance of decoding algorithms on the calibration or enabling calibration with the minimal burden on the user. A potential solution could be a pre-trained decoder demonstrating a reasonable accuracy on the naive operators. Addressing this issue, we considered ambiguous stimuli classification tasks and trained an artificial neural network to classify brain responses to the stimuli of low and high ambiguity. We built a pre-trained classifier utilizing time-frequency features corresponding to the fundamental neurophysiological processes shared between subjects. To extract these features, we statistically contrasted electroencephalographic (EEG) spectral power between the classes in the representative group of subjects. As a result, the pre-trained classifier achieved 74% accuracy on the data of newly recruited subjects. Analysis of the literature suggested that a pre-trained classifier could help naive users to start using BCI bypassing training and further increased accuracy during the feedback session. Thus, our results contribute to using BCI during paralysis or limb amputation when there is no explicit user-generated kinematic output to properly train a decoder. In machine learning, our approach may facilitate the development of transfer learning (TL) methods for addressing the cross-subject problem. It allows extracting the interpretable feature subspace from the source data (the representative group of subjects) related to the target data (a naive user), preventing the negative transfer in the cross-subject tasks.

Monitoring the Cortical Activity of Children and Adults during Cognitive Task Completion.

In this paper, we used an EEG system to monitor and analyze the cortical activity of children and adults at a sensor level during cognitive tasks in the form of a Schulte table. This complex cognitive task simultaneously involves several cognitive processes and systems: visual search, working memory, and mental arithmetic. We revealed that adults found numbers on average two times faster than children in the beginning. However, this difference diminished at the end of table completion to 1.8 times. In children, the EEG analysis revealed high parietal alpha-band power at the end of the task. This indicates the shift from procedural strategy to less demanding fact-retrieval. In adults, the frontal beta-band power increased at the end of the task. It reflects enhanced reliance on the top-down mechanisms, cognitive control, or attentional modulation rather than a change in arithmetic strategy. Finally, the alpha-band power of adults exceeded one of the children in the left hemisphere, providing potential evidence for the fact-retrieval strategy. Since the completion of the Schulte table involves a whole set of elementary cognitive functions, the obtained results were essential for developing passive brain-computer interfaces for monitoring and adjusting a human state in the process of learning and solving cognitive tasks of various types.

Sensor-Level Wavelet Analysis Reveals EEG Biomarkers of Perceptual Decision-Making.

Perceptual decision-making requires transforming sensory information into decisions. An ambiguity of sensory input affects perceptual decisions inducing specific time-frequency patterns on EEG (electroencephalogram) signals. This paper uses a wavelet-based method to analyze how ambiguity affects EEG features during a perceptual decision-making task. We observe that parietal and temporal beta-band wavelet power monotonically increases throughout the perceptual process. Ambiguity induces high frontal beta-band power at 0.3-0.6 s post-stimulus onset. It may reflect the increasing reliance on the top-down mechanisms to facilitate accumulating decision-relevant sensory features. Finally, this study analyzes the perceptual process using mixed within-trial and within-subject design. First, we found significant percept-related changes in each subject and then test their significance at the group level. Thus, observed beta-band biomarkers are pronounced in single EEG trials and may serve as control commands for brain-computer interface (BCI).

Effect of repetition on the behavioral and neuronal responses to ambiguous Necker cube images.

A repeated presentation of an item facilitates its subsequent detection or identification, a phenomenon of priming. Priming may involve different types of memory and attention and affects neural activity in various brain regions. Here we instructed participants to report on the orientation of repeatedly presented Necker cubes with high (HA) and low (LA) ambiguity. Manipulating the contrast of internal edges, we varied the ambiguity and orientation of the cube. We tested how both the repeated orientation (referred to as a stimulus factor) and the repeated ambiguity (referred to as a top-down factor) modulated neuronal and behavioral response. On the behavioral level, we observed higher speed and correctness of the response to the HA stimulus following the HA stimulus and a faster response to the right-oriented LA stimulus following the right-oriented stimulus. On the neuronal level, the prestimulus theta-band power grew for the repeated HA stimulus, indicating activation of the neural networks related to attention and uncertainty processing. The repeated HA stimulus enhanced hippocampal activation after stimulus onset. The right-oriented LA stimulus following the right-oriented stimulus enhanced activity in the precuneus and the left frontal gyri before the behavioral response. During the repeated HA stimulus processing, enhanced hippocampal activation may evidence retrieving information to disambiguate the stimulus and define its orientation. Increased activation of the precuneus and the left prefrontal cortex before responding to the right-oriented LA stimulus following the right-oriented stimulus may indicate a match between their orientations. Finally, we observed increased hippocampal activation after responding to the stimuli, reflecting the encoding stimulus features in memory. In line with the large body of works relating the hippocampal activity with episodic memory, we suppose that this type of memory may subserve the priming effect during the repeated presentation of ambiguous images.

Dissociating Cognitive Processes During Ambiguous Information Processing in Perceptual Decision-Making.

Decision-making requires the accumulation of sensory evidence. However, in everyday life, sensory information is often ambiguous and contains decision-irrelevant features. This means that the brain must disambiguate sensory input and extract decision-relevant features. Sensory information processing and decision-making represent two subsequent stages of the perceptual decision-making process. While sensory processing relies on occipito-parietal neuronal activity during the earlier time window, decision-making lasts for a prolonged time, involving parietal and frontal areas. Although perceptual decision-making is being actively studied, its neuronal mechanisms under ambiguous sensory evidence lack detailed consideration. Here, we analyzed the brain activity of subjects accomplishing a perceptual decision-making task involving the classification of ambiguous stimuli. We demonstrated that ambiguity induced high frontal θ-band power for 0.15 s post-stimulus onset, indicating increased reliance on top-down processes, such as expectations and memory. Ambiguous processing also caused high occipito-parietal ß-band power for 0.2 s and high fronto-parietal ß-power for 0.35-0.42 s post-stimulus onset. We supposed that the former component reflected the disambiguation process while the latter reflected the decision-making phase. Our findings complemented existing knowledge about ambiguous perception by providing additional information regarding the temporal discrepancy between the different cognitive processes during perceptual decision-making.

Ectopia cordis: a rare congenital anomaly.

Ectopia cordis (EC) is a rare congenital anomaly associated with the heart positioned outside of the thoracic cavity either partially or completely. The ectopic heart can be found along a spectrum of anatomical locations, including the cervical, thoracic and abdominal regions and in most cases, it protrudes outside the chest through a split sternum. Although the first case of EC was identified during the early 1600s only 91 cases have been reported since then in the literature. This review will discuss the history and prevalence of EC, its etiology, morphology, presentation and symptoms, complications, diagnosis, treatment and management and prognosis.