Evaluating inter-individual variability captured by the Eleveld pharmacokinetics model.

Inter-individual variability in Pharmacokinetic (PK) and Pharmacodynamic (PD) models significantly affects the accuracy of Target Controlled Infusion and closed-loop control of anesthesia. We hypothesize that the novel Eleveld PK model captures more inter-individual variability relevant to both open-loop and closed-loop control design, resulting in reduced variability in PD models identified using the Eleveld PK model's plasma prediction compared to the Schuttler or Schnider PK model. We used a dataset of propofol infusion rates and Depth of Hypnosis measurements across three demographic groups: elderly, obese, and adult. PD models are identified based on plasma concentration prediction using three PK models (Schuttler, Schnider, and Eleveld). Validation methods are presented to confirm acceptable predictive performance and comparable PK-PD model variability within each demographic group. To test our hypothesis, we compared coefficient variations in step responses for open-loop control and multiplicative uncertainty of PD model sets for closed-loop control. Validated PKPD models using the Schuttler and Schnider PK model showed no significant differences in predictive response and multiplicative uncertainty compared to the Eleveld PK model. The coefficient variations in step responses of PD model sets and the frequency ranges, corresponding to uncertainty below one, were comparable for all three PK models. The comparison of the accumulated coefficient of variation in the step-response and the uncertainty of the PD model sets indicated that the Eleveld PK model does not offer any advantage for the design of open-loop or closed-loop control of anesthesia.

Choosing blood pressure thresholds to inform pregnancy care in the community: An analysis of cluster trials.

OBJECTIVE: To inform digital health design by evaluating diagnostic test properties of antenatal blood pressure (BP) outputs and levels to identify women at risk of adverse outcomes. DESIGN: Planned secondary analysis of cluster randomised trials. SETTING: India, Pakistan, Mozambique. POPULATION: Women with in-community BP measurements and known pregnancy outcomes. METHODS: Blood pressure was defined by its outputs (systolic and/or diastolic, systolic only, diastolic only or mean arterial pressure [calculated]) and level: normotension-1 (<135/85 mmHg), normotension-2 (135-139/85-89 mmHg), non-severe hypertension (140-149/90-99 mmHg; 150-154/100-104 mmHg; 155-159/105-109 mmHg) and severe hypertension (≥160/110 mmHg). Dose-response (adjusted risk ratio [aRR]) and diagnostic test properties (negative [-LR] and positive [+LR] likelihood ratios) were estimated. MAIN OUTCOME MEASURES: Maternal/perinatal composites of mortality/morbidity. RESULTS: Among 21 069 pregnancies, different BP outputs had similar aRR, -LR, and +LR for adverse outcomes. No BP level (even normotension-1) was associated with low risk (all -LR ≥0.20). Across outcomes, risks rose progressively with higher BP levels above normotension-1. For each of maternal central nervous system events and stillbirth, BP ≥155/105 mmHg showed at least good diagnostic test performance (+LR ≥5.0) and BP ≥135/85 mmHg at least fair performance, similar to BP ≥140/90 mmHg (+LR 2.0-4.99). CONCLUSIONS: In the community, normal BP values do not provide reassurance about subsequent adverse outcomes. Given the similar performance of BP cut-offs of 135/85 and 140/90 mmHg for hypertension, and 155/105 and 160/110 mmHg for severe hypertension, digital decision support for women in the community should consider using these lower thresholds.

The Effect of Low-Dose Intraoperative Ketamine on Closed-Loop-Controlled General Anesthesia: A Randomized Controlled Equivalence Trial.

BACKGROUND: Closed-loop control of propofol-remifentanil anesthesia using the processed electroencephalography depth-of-hypnosis index provided by the NeuroSENSE monitor (WAVCNS) has been previously described. The purpose of this placebo-controlled study was to evaluate the performance (percentage time within ±10 units of the setpoint during the maintenance of anesthesia) of a closed-loop propofol-remifentanil controller during induction and maintenance of anesthesia in the presence of a low dose of ketamine. METHODS: Following ethical approval and informed consent, American Society of Anesthesiologist (ASA) physical status I-II patients aged 19-54 years, scheduled for elective orthopedic surgery requiring general anesthesia for >60 minutes duration, were enrolled in a double-blind randomized, placebo-controlled, 2-group equivalence trial. Immediately before induction of anesthesia, participants in the ketamine group received a 0.25 mg·kg-1 bolus of intravenous ketamine over 60 seconds followed by a continuous 5 µg·kg-1·min-1 infusion for up to 45 minutes. Participants in the control group received an equivalent volume of normal saline. After the initial study drug bolus, closed-loop induction of anesthesia was initiated; propofol and remifentanil remained under closed-loop control until the anesthetic was tapered and turned off at the anesthesiologist's discretion. An equivalence range of ±8.99% was assumed for comparing controller performance. RESULTS: Sixty patients participated: 41 males, 54 ASA physical status I, with a median (interquartile range [IQR]) age of 29 [23, 38] years and weight of 82 [71, 93] kg. Complete data were available from 29 cases in the ketamine group and 27 in the control group. Percentage time within ±10 units of the WAVCNS setpoint was median [IQR] 86.6% [79.7, 90.2] in the ketamine group and 86.4% [76.5, 89.8] in the control group (median difference, 1.0%; 95% confidence interval [CI] -3.6 to 5.0). Mean propofol dose during maintenance of anesthesia for the ketamine group was higher than for the control group (median difference, 24.9 µg·kg-1·min-1; 95% CI, 6.5-43.1; P = .005). CONCLUSIONS: Because the 95% CI of the difference in controller performance lies entirely within the a priori equivalence range, we infer that this analgesic dose of ketamine did not alter controller performance. Further study is required to confirm the finding that mean propofol dosing was higher in the ketamine group, and to investigate the implication that this dose of ketamine may have affected the WAVCNS.

Effect of ketamine on the NeuroSENSE WAVCNS during propofol anesthesia; a randomized feasibility trial.

Dose-dependent effects of ketamine on processed electroencephalographic depth-of-hypnosis indices have been reported. Limited data are available for the NeuroSENSE WAVCNS index. Our aim was to establish the feasibility of closed-loop propofol-remifentanil anesthesia guided by the WAVCNS index in the presence of an analgesic dose of ketamine. Thirty ASA I-II adults, 18-54 years, requiring general anesthesia for anterior cruciate ligament surgery were randomized to receive: full-dose [ketamine, 0.5 mg kg-1 initial bolus, 10 mcg kg-1 min-1 infusion] (recommended dose for postoperative pain management); half-dose [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion]; or control [no ketamine]. After the ketamine bolus, patients received 1.0 mcg kg-1 remifentanil over 30 s, then 1.5 mg kg-1 propofol over 30 s, followed by manually-adjusted propofol-remifentanil anesthesia. The WAVCNS was > 60 for 7/9 patients in the full-dose group at 7 min after starting the propofol infusion. This was inconsistent with clinical observations of depth-of-hypnosis and significantly higher than control (median difference [MD] 17.0, 95% confidence interval [CI] 11.4-26.8). WAVCNS was median [interquartile range] 49.3 [42.2-62.6] in the half-dose group, and not different to control (MD 5.1, 95% CI - 4.9 to 17.9). During maintenance of anesthesia, the WAVCNS was higher in the full-dose group compared to control (MD 14.7, 95% CI 10.2-19.2) and in the half-dose group compared to control (MD 11.4, 95% CI 4.7-20.4). The full-dose of ketamine recommended for postoperative pain management had a significant effect on the WAVCNS. This effect should be considered when using the WAVCNS to guide propofol-remifentanil dosing.Trial Registration ClinicalTrails.gov No. NCT02908945.

Evaluating NeuroSENSE for assessing depth of hypnosis during desflurane anesthesia: an adaptive, randomized-controlled trial.

PURPOSE: Processed electroencephalography (EEG) monitors support depth-of-hypnosis assessment during anesthesia. This randomized-controlled trial investigated the performance of the NeuroSENSE electroencephalography (EEG) monitor to determine whether its wavelet anesthetic value for central nervous system (WAVCNS) index distinguishes consciousness from unconsciousness during induction of anesthesia (as assessed by the anesthesiologist) and emergence from anesthesia (indicated by patient responsiveness), and whether it correlates with changes in desflurane minimum alveolar concentration (MAC) during maintenance of anesthesia. METHODS: EEG was collected using a fronto-temporal bilateral montage. The WAVCNS was continuously recorded by the NeuroSENSE monitor, to which the anesthesiologist was blinded. Anesthesia was induced with propofol/remifentanil and maintained with desflurane, with randomized changes of -0.4, 0, or +0.4 MAC every 7.5 min within the 0.8-1.6 MAC range, if clinically acceptable to the anesthesiologist. During emergence from anesthesia, desflurane was stepped down by 0.2 MAC every five minutes. RESULTS: Data from 75 patients with a median [interquartile range] age of 41[35-52] yr were obtained. The WAVCNS distinguished consciousness from unconsciousness as assessed by the anesthesiologist, with area under the receiver operating characteristic curve of 99.5% (95% confidence interval [CI], 98.5 to 100.0) at loss of consciousness and 99.4% (95% CI, 98.5 to 100.0) at return of consciousness. Bilateral WAVCNS changes correlated with desflurane concentrations, with -8.0 and -8.6 WAVCNS units, respectively, per 1 MAC change in the 0.8-1.6 MAC range during maintenance of anesthesia and -10.0 and -10.5 WAVCNS units, respectively, in the 0.4-1.6 MAC range including emergence from anesthesia. CONCLUSION: The NeuroSENSE monitor can reliably discriminate between consciousness and unconsciousness, as assessed by the anesthesiologist, during induction of anesthesia and with a lower level of reliability during emergence from anesthesia. The WAVCNS correlates with desflurane concentration but plateaus at higher concentrations, similar to other EEG monitors, which suggests limited utility to titrate higher concentrations of anesthetic vapour. TRIAL REGISTRATION: clinicaltrials.gov, NCT02088671; registered 17 March, 2014.

Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and Safety System.

BACKGROUND: Closed-loop control of anesthesia involves continual adjustment of drug infusion rates according to measured clinical effect. The NeuroSENSE monitor provides an electroencephalographic measure of depth of hypnosis (wavelet-based anesthetic value for central nervous system monitoring [WAVCNS]). It has previously been used as feedback for closed-loop control of propofol, in a system designed using robust control engineering principles, which implements features specifically designed to ensure patient safety. Closed-loop control of a second drug, remifentanil, may be added to improve WAVCNS stability in the presence of variable surgical stimulation. The objective of this study was to design and evaluate the feasibility of a closed-loop system for robust control of propofol and remifentanil infusions using WAVCNS feedback, with an infusion safety system based on the known pharmacological characteristics of these 2 drugs. METHODS: With Health Canada authorization, research ethics board approval, and informed consent, American Society of Anesthesiologists I-III adults, requiring general anesthesia for elective surgery, were enrolled in a 2-phase study. In both phases, infusion of propofol was controlled in closed loop during induction and maintenance of anesthesia, using WAVCNS feedback, but bounded by upper- and lower-estimated effect-site concentration limits. In phase I, remifentanil was administered using an adjustable target-controlled infusion and a controller was designed based on the collected data. In phase II, remifentanil was automatically titrated to counteract rapid increases in WAVCNS. RESULTS: Data were analyzed for 127 patients, of median (range) age 64 (22-86) years, undergoing surgical procedures lasting 105 (9-348) minutes, with 52 participating in phase I and 75 in phase II. The overall control performance indicator, global score, was a median (interquartile range) 18.3 (14.2-27.7) in phase I and 14.6 (11.6-20.7) in phase II (median difference, -3.25; 95% confidence interval, -6.35 to -0.52). The WAVCNS was within ±10 of the setpoint for 84.3% (76.6-90.6) of the maintenance of anesthesia in phase I and 88.2% (83.1-93.4) in phase II (median difference, 3.7; 95% confidence interval, 0.1-6.9). The lower propofol safety bound was activated during 30 of 52 (58%) cases in phase I and 51 of 75 (68%) cases in phase II. CONCLUSIONS: Adding closed-loop control of remifentanil improved overall controller performance. This controller design offers a robust method to optimize the control of 2 drugs using a single sensor. The infusion safety system is an important component of a robust automated anesthesia system, but further research is required to determine the optimal constraints for these safe conditions.

Feasibility of continuous sedation monitoring in critically ill intensive care unit patients using the NeuroSENSE WAVCNS index.

Sedation in the intensive care unit (ICU) is challenging, as both over- and under-sedation are detrimental. Current methods of assessment, such as the Richmond Agitation Sedation Scale (RASS), are measured intermittently and rely on patients' behavioral response to stimulation, which may interrupt sleep/rest. A non-stimulating method for continuous sedation monitoring may be beneficial and allow more frequent assessment. Processed electroencephalography (EEG) monitors have not been routinely adopted in the ICU. The aim of this observational study was to assess the feasibility of using the NeuroSENSE™ monitor for EEG-based continuous sedation assessment. With ethical approval, ICU patients on continuous propofol sedation were recruited. Depth-of-hypnosis index (WAVCNS) values were obtained from the NeuroSENSE. Bedside nurses, blinded to the NeuroSENSE, performed regular RASS assessments and maintained the sedation regimen as per standard of care. Participants were monitored throughout the duration of their propofol infusion, up to 24 h. Fifteen patients, with median [interquartile range] age of 57 [52-62.5] years were each monitored for a duration of 9.0 [5.7-20.1] h. Valid WAVCNS values were obtained for 89% [66-99] of monitoring time and were widely distributed within and between individuals, with 6% [1-31] spent < 40 (very deep), and 3% [1-15] spent > 90 (awake). Significant EEG suppression was detected in 3/15 (20%) participants. Observed RASS matched RASS goals in 36/89 (40%) assessments. The WAVCNS variability, and incidence of EEG suppression, highlight the limitations of using RASS as a standalone sedation measure, and suggests potential benefit of adjunct continuous brain monitoring.

A delayed functional observer/predictor with bounded-error for depth of hypnosis monitoring.

With the motivation of providing safety for a patient under anesthesia, this paper suggests conditions for evaluating the correctness of an available user interface for systems under shared control based on observability and predictability requirements. Situation awareness is necessary for the user to make correct decisions about the inputs. In this article, we develop a technique to investigate the conditions under which an anesthetists can attain situation awareness about a limited but important aspect of anesthesia, namely depth of hypnosis (DOH). Furthermore, we consider that, in practice, to attain situation awareness, the estimation of the task states does not necessarily need to be precise but can be bounded within certain margins. Hence, attaining situation awareness about DOH is modeled as a bounded-error delayed functional observation/prediction. Unless such an observer/predictor exists for a system with a given user-interface, the safety of the operation may be compromised. The suggested technique proves that, in order to provide safety for the patient under anesthesia, it is necessary for the anesthetist to have access to the predictive information from a clinical decision support system.

Feedback control for clinicians.

Although feedback control and automation has revolutionized many fields of human activity, it has yet to have a significant impact on healthcare, particularly when a patient is in the loop. Although there have been a number of studies concerned with closed-loop control of anesthesia, they have yet to have an impact on clinical practice. For such systems to be successful, engineers and clinicians have to work hand in hand, for this they have to have a basic understanding of each other's fields. The goal of this paper is to introduce clinicians to basic concepts in control engineering, with an emphasis on the properties of feedback control. Concepts such as modelling for control, feedback and uncertainty, robustness, feedback controller such as proportional-integral-derivative control, predictive control and adaptive control are briefly reviewed. Finally we discuss the safety issues around closed-loop control and discuss ways by which safe control can be guaranteed.

Geographical validation of the Smart Triage Model by age group.

Infectious diseases in neonates account for half of the under-five mortality in low- and middle-income countries. Data-driven algorithms such as clinical prediction models can be used to efficiently detect critically ill children in order to optimize care and reduce mortality. Thus far, only a handful of prediction models have been externally validated and are limited to neonatal in-hospital mortality. The aim of this study is to externally validate a previously derived clinical prediction model (Smart Triage) using a combined prospective baseline cohort from Uganda and Kenya with a composite endpoint of hospital admission, mortality, and readmission. We evaluated model discrimination using area under the receiver-operator curve (AUROC) and visualized calibration plots with age subsets (< 30 days, ≤ 2 months, ≤ 6 months, and < 5 years). Due to reduced performance in neonates (< 1 month), we re-estimated the intercept and coefficients and selected new thresholds to maximize sensitivity and specificity. 11595 participants under the age of five (under-5) were included in the analysis. The proportion with an endpoint ranged from 8.9% in all children under-5 (including neonates) to 26% in the neonatal subset alone. The model achieved good discrimination for children under-5 with AUROC of 0.81 (95% CI: 0.79-0.82) but poor discrimination for neonates with AUROC of 0.62 (95% CI: 0.55-0.70). Sensitivity at the low-risk thresholds (CI) were 85% (83%-87%) and 68% (58%-76%) for children under-5 and neonates, respectively. After model revision for neonates, we achieved an AUROC of 0.83 (95% CI: 0.79-0.87) with 13% and 41% as the low- and high-risk thresholds, respectively. The updated Smart Triage performs well in its predictive ability across different age groups and can be incorporated into current triage guidelines at local healthcare facilities. Additional validation of the model is indicated, especially for the neonatal model.

Closed-loop control of anesthesia: a primer for anesthesiologists.

Feedback control is ubiquitous in nature and engineering and has revolutionized safety in fields from space travel to the automobile. In anesthesia, automated feedback control holds the promise of limiting the effects on performance of individual patient variability, optimizing the workload of the anesthesiologist, increasing the time spent in a more desirable clinical state, and ultimately improving the safety and quality of anesthesia care. The benefits of control systems will not be realized without widespread support from the health care team in close collaboration with industrial partners. In this review, we provide an introduction to the established field of control systems research for the everyday anesthesiologist. We introduce important concepts such as feedback and modeling specific to control problems and provide insight into design requirements for guaranteeing the safety and performance of feedback control systems. We focus our discussion on the optimization of anesthetic drug administration.

An evaluation of an expert system for detecting critical events during anesthesia in a human patient simulator: a prospective randomized controlled study.

BACKGROUND: Perioperative monitoring systems produce a large amount of uninterpreted data, use threshold alarms prone to artifacts, and rely on the clinician to continuously visually track changes in physiological data. To address these deficiencies, we developed an expert system that provides real-time clinical decisions for the identification of critical events. We evaluated the efficacy of the expert system for enhancing critical event detection in a simulated environment. We hypothesized that anesthesiologists would identify critical ventilatory events more rapidly and accurately with the expert system. METHODS: We used a high-fidelity human patient simulator to simulate an operating room environment. Participants managed 4 scenarios (anesthetic vapor overdose, tension pneumothorax, anaphylaxis, and endotracheal tube cuff leak) in random order. In 2 of their 4 scenarios, participants were randomly assigned to the expert system, which provided trend-based alerts and potential differential diagnoses. Time to detection and time to treatment were measured. Workload questionnaires and structured debriefings were completed after each scenario, and a usability questionnaire at the conclusion of the session. Data were analyzed using a mixed-effects linear regression model; Fisher exact test was used for workload scores. RESULTS: Twenty anesthesiology trainees and 15 staff anesthesiologists with a combined median (range) of 36 (29-66) years of age and 6 (1-38) years of anesthesia experience participated. For the endotracheal tube cuff leak, the expert system caused mean reductions of 128 (99% confidence interval [CI], 54-202) seconds in time to detection and 140 (99% CI, 79-200) seconds in time to treatment. In the other 3 scenarios, a best-case decrease of 97 seconds (lower 99% CI) in time to diagnosis for anaphylaxis and a worst-case increase of 63 seconds (upper 99% CI) in time to treatment for anesthetic vapor overdose were found. Participants were highly satisfied with the expert system (median score, 2 on a scale of 1-7). Based on participant debriefings, we identified avoidance of task fixation, reassurance to initiate invasive treatment, and confirmation of a suspected diagnosis as 3 safety-critical areas. CONCLUSION: When using the expert system, clinically important and statistically significant decreases in time to detection and time to treatment were observed for the endotracheal tube cuff Leak scenario. The observed differences in the other 3 scenarios were much smaller and not statistically significant. Further evaluation is required to confirm the clinical utility of real-time expert systems for anesthesia.

Robust closed-loop control of induction and maintenance of propofol anesthesia in children.

BACKGROUND: During closed-loop control, a drug infusion is continually adjusted according to a measure of clinical effect (e.g., an electroencephalographic depth of hypnosis (DoH) index). Inconsistency in population-derived pediatric pharmacokinetic/pharmacodynamic models and the large interpatient variability observed in children suggest a role for closed-loop control in optimizing the administration of intravenous anesthesia. OBJECTIVE: To clinically evaluate a robustly tuned system for closed-loop control of the induction and maintenance of propofol anesthesia in children undergoing gastrointestinal endoscopy. METHODS: One hundred and eight children, aged 6-17, ASA I-II, were enrolled. Prior to induction of anesthesia, NeuroSENSE™ sensors were applied to obtain the WAVCNS DoH index. An intravenous cannula was inserted and lidocaine (0.5 mg·kg(-1) ) administered. Remifentanil was administered as a bolus (0.5 µg·kg(-1) ), followed by continuous infusion (0.03 µg·kg(-1) ·min(-1) ). The propofol infusion was closed-loop controlled throughout induction and maintenance of anesthesia, using WAVCNS as feedback. RESULTS: Anesthesia was closed-loop controlled in 102 cases. The system achieved and maintained an adequate DoH without manual adjustment in 87/102 (85%) cases. Induction of anesthesia (to WAVCNS  ≤ 60) was completed in median 3.8 min (interquartile range (IQR) 3.1-5.0), culminating in a propofol effect-site concentration (Ce ) of median 3.5 µg·ml(-1) (IQR 2.7-4.5). During maintenance of anesthesia, WAVCNS was measured within 10 units of the target for median 89% (IQR 79-96) of the time. Spontaneous breathing required no manual intervention in 91/102 (89%) cases. CONCLUSIONS: A robust closed-loop system can provide effective propofol administration during induction and maintenance of anesthesia in children. Wide variation in the calculated Ce highlights the limitation of open-loop regimes based on pharmacokinetic/pharmacodynamic models.

Design and evaluation of a low-cost smartphone pulse oximeter.

Infectious diseases such as pneumonia take the lives of millions of children in low- and middle-income countries every year. Many of these deaths could be prevented with the availability of robust and low-cost diagnostic tools using integrated sensor technology. Pulse oximetry in particular, offers a unique non-invasive and specific test for an increase in the severity of many infectious diseases such as pneumonia. If pulse oximetry could be delivered on widely available mobile phones, it could become a compelling solution to global health challenges. Many lives could be saved if this technology was disseminated effectively in the affected regions of the world to rescue patients from the fatal consequences of these infectious diseases. We describe the implementation of such an oximeter that interfaces a conventional clinical oximeter finger sensor with a smartphone through the headset jack audio interface, and present a simulator-based systematic verification system to be used for automated validation of the sensor interface on different smartphones and media players. An excellent agreement was found between the simulator and the audio oximeter for both oxygen saturation and heart rate over a wide range of optical transmission levels on 4th and 5th generations of the iPod TouchTM and iPhoneTM devices.

Monitoring nociception during general anesthesia with cardiorespiratory coherence.

A novel wavelet transform cardiorespiratory coherence (WTCRC) algorithm has been developed to measure the autonomic state. WTCRC may be used as a nociception index, ranging from 0 (no nociception, strong coherence) to 100 (strong nociception, low coherence). The aim of this study is to estimate the sensitivity of the algorithm to nociception (dental dam insertions) and antinociception (bolus doses of anesthetic drugs). WTCRC's sensitivity is compared to mean heart rate (HRmean) and mean non-invasive blood pressure (NIBPmean), which are commonly used clinical signs. Data were collected from 48 children receiving general anesthesia during dental surgery. The times of dental dam insertion and anesthetic bolus events were noted in real-time during surgeries. 42 dental dam insertion and 57 anesthetic bolus events were analyzed. The change in average WTCRC, HRmean, and NIBPmean was calculated between a baseline period before each event and a response period after. A Wilcoxon rank-sum test was used to compare changes. Dental dam insertion changed the WTCRC nociception index by an average of 14 (82 %) [95 % CI from 7.4 to 19], HRmean by 7.3 beats/min (8.1 %) [5.6-9.6], and NIBPmean by 8.3 mmHg (12 %) [4.9-13]. A bolus dose of anesthetics changed the WTCRC by -15 (-50 %) [-21 to -9.3], HRmean by -4.8 beats/min (4.6 %) [-6.6 to -2.9], and NIBPmean by -2.6 mmHg (3.4 %) [-4.7 to -0.50]. A nociception index based on cardiorespiratory coherence is more sensitive to nociception and antinociception than are HRmean or NIBPmean. The WTCRC algorithm shows promise for noninvasively monitoring nociception during general anesthesia.

Effective pandemic policy design through feedback does not need accurate predictions.

The COVID-19 pandemic has had an enormous toll on human health and well-being and led to major social and economic disruptions. Public health interventions in response to burgeoning case numbers and hospitalizations have repeatedly bent down the epidemic curve, effectively creating a feedback control system. Worst case scenarios have been avoided in many places through this responsive feedback. We aim to formalize and illustrate how to incorporate principles of feedback control into pandemic projections and decision-making, and ultimately shift the focus from prediction to the design of interventions. Starting with an epidemiological model for COVID-19, we illustrate how feedback control can be incorporated into pandemic management using a simple design that couples recent changes in case numbers or hospital occupancy with explicit policy restrictions. We demonstrate robust ability to control a pandemic using a design that responds to hospital cases, despite simulating large uncertainty in reproduction number R0 (range: 1.04-5.18) and average time to hospital admission (range: 4-28 days). We show that shorter delays, responding to case counts versus hospital measured infections, reduce both the cumulative case count and the average level of interventions. Finally, we show that feedback is robust to changing compliance to public health directives and to systemic changes associated with variants of concern and with the introduction of a vaccination program. The negative impact of a pandemic on human health and societal disruption can be reduced by coupling models of disease propagation with models of the decision-making process. In contrast to highly varying open-loop projections, incorporating feedback explicitly in the decision-making process is more reflective of the real-world challenge facing public health decision makers. Using feedback principles, effective control strategies can be designed even if the pandemic characteristics are highly uncertain, encouraging earlier and smaller actions that reduce both case counts and the extent of interventions.

Detection of spreading depression features from the scalp of epileptic patients.

Spreading depression (SD), a pathological cortical negative DC potential, is caused by an elevation of potassium ions in the extracellular space. This leads to a transient relocation of ions within neurons and a slow spread through brain tissue. Our previous research established a correlation between scalp SD and seizures in patients with intractable epilepsy using our novel electroencephalography (EEG). In this study, we enhanced our EEG system by incorporating a Near-infrared spectroscopy (NIRS) module for multi-modal EEG-NIRS measurements. The aim is to provide an investigation into the defining characteristics and methods for detecting SD.Clinical Relevance-: The detection of SD serves as a novel biomarker for epilepsy, capable of forewarning seizures within a time range from 10 secs to 30 min. This detection plays a crucial role in predicting and preventing seizures and providing diagnostic information for drug-resistant epilepsy patients.

Blink-related EEG oscillations are neurophysiological indicators of subconcussive head impacts in female soccer players: a preliminary study.

Introduction: Repetitive subconcussive head impacts can lead to subtle neural changes and functional consequences on brain health. However, the objective assessment of these changes remains limited. Resting state blink-related oscillations (BROs), recently discovered neurological responses following spontaneous blinking, are explored in this study to evaluate changes in BRO responses in subconcussive head impacts. Methods: We collected 5-min resting-state electroencephalography (EEG) data from two cohorts of collegiate athletes who were engaged in contact sports (SC) or non-contact sports (HC). Video recordings of all on-field activities were conducted to determine the number of head impacts during games and practices in the SC group. Results: In both groups, we were able to detect a BRO response. Following one season of games and practice, we found a strong association between the number of head impacts sustained by the SC group and increases in delta and beta spectral power post-blink. There was also a significant difference between the two groups in the morphology of BRO responses, including decreased peak-to-peak amplitude of response over left parietal channels and differences in spectral power in delta and alpha frequency range post-blink. Discussion: Our preliminary results suggest that the BRO response may be a useful biomarker for detecting subtle neural changes resulting from repetitive head impacts. The clinical utility of this biomarker will need to be validated through further research with larger sample sizes, involving both male and female participants, using a longitudinal design.

Neonatal Face and Facial Landmark Detection from Video Recordings.

This paper explores automated face and facial landmark detection of neonates, which is an important first step in many video-based neonatal health applications, such as vital sign estimation, pain assessment, sleep-wake classification, and jaundice detection. Utilising three publicly available datasets of neonates in the clinical environment, 366 images (258 subjects) and 89 (66 subjects) were annotated for training and testing, respectively. Transfer learning was applied to two YOLO-based models, with input training images augmented with random horizontal flipping, photo-metric colour distortion, translation and scaling during each training epoch. Additionally, the re-orientation of input images and fusion of trained deep learning models was explored. Our proposed model based on YOLOv7Face outperformed existing methods with a mean average precision of 84.8% for face detection, and a normalised mean error of 0.072 for facial landmark detection. Overall, this will assist in the development of fully automated neonatal health assessment algorithms.Clinical relevance- Accurate face and facial landmark detection provides an automated and non-contact option to assist in video-based neonatal health applications.

Concurrent recordings of slow DC-potentials and epileptiform discharges: Novel EEG amplifier and signal processing techniques.

Ionic currents within the brain generate voltage oscillations. These bioelectrical activities include ultra-low frequency electroencephalograms (DC-EEG, frequency less than 0.1 Hz) and conventional clinical electroencephalograms (AC-EEG, 0.5-70 Hz). Although AC-EEG is commonly used for diagnosing epilepsy, recent studies indicate that DC-EEG is an essential frequency component of EEG and can provide valuable information for analyzing epileptiform discharges. During conventional EEG recordings, DC-EEG is censored by applying high-pass filtering to i) obliterate slow-wave artifacts, ii) eliminate the bioelectrodes' half-cell potential asymmetrical changes in ultralow-low frequency, and iii) prevent instrument saturation. Spreading depression (SD), which is the most prolonged fluctuation in DC-EEG, may be associated with epileptiform discharges. However, recording of SD signals from the scalp's surface can be challenging due to the filtering effect and non-neuronal slow shift potentials. In this study, we describe a novel technique to extend the frequency bandwidth of surface EEG to record SD signals. The method includes novel instrumentation, appropriate bioelectrodes, and efficient signal-processing techniques. To evaluate the accuracy of our approach, we performed a simultaneous surface recording of DC- and AC-EEG from epileptic patients during long-term video EEG monitoring, which provide a promising tool for diagnosis of epilepsy. DATA AVAILABILITY STATEMENT: The data presented in this study are available on request.