A non-invasive wearable stress patch for real-time cortisol monitoring using a pseudoknot-assisted aptamer.

Stress is part of everyone's life and is exacerbated by traumatic events such as pandemics, disasters, violence, lifestyle changes, and health disorders. Chronic stress has many detrimental health effects and can even be life-threatening. Long-term stress monitoring outside of a hospital is often accomplished by measuring heart rate variability. While easy to measure, this digital biomarker has low specificity, greatly limiting its utility. To address this shortcoming, we report a non-invasive, wearable biomolecular sensor to monitor cortisol levels in sweat. Cortisol is a neuroendocrine hormone that regulates homeostasis as part of the stress pathway. Cortisol is detected using an electrochemical sensor functionalized with a pseudoknot-assisted aptamer and a flexible microfluidic sweat sampling system. The skin-worn microfluidic sampler provides rapid sweat collection while separating old and new sweat. The conformation-switching aptamer provides high specificity towards cortisol while being regenerable, allowing it to monitor temporal changes continuously. The aptamer was engineered to add a pseudoknot, restricting it to only two states, thus minimizing the background signal and enabling high sensitivity. An electrochemical pH sensor allows pH-corrected amperometric measurements. Device operation was demonstrated invitro with a broad linear dynamic range (1 pM - 1 µM) covering the physiological range and a sub-picomolar (0.2 pM) limit of detection in sweat. Real-time, on-body measurements were collected from human subjects using an induced stress protocol, demonstrating in-situ signal regeneration and the ability to detect dynamic cortisol fluctuations continuously for up to 90 min. The reported device has the potential to improve prognosis and enable personalized treatments.

Asistencia del recién nacido con hernia diafragmática congénita / Care of newborns with congenital diaphragmatic hernia / Cuidados ao recém-nascido com hérnia diafragmática congênita

La hernia diafragmática congénita es un defecto en el diafragma que lleva a la herniación del contenido abdominal a la cavidad torácica durante el período intrauterino. La morbimortalidad está determinada por la asociación con otras malformaciones, el grado de hipoplasia pulmonar y la presencia de hipertensión pulmonar secundaria. Presenta una incidencia estimada de 1 cada 2.500-3.000 recién nacidos vivos, constituyendo en un 60% una malformación aislada. Es una patología evolutiva que puede ser diagnosticada a partir de la semana 20-24, la ubicación más habitual es la posterolateral izquierda. Se trata de una patología que requiere ingreso a cuidados intensivos al nacimiento y luego de lograda la estabilización del paciente es de sanción quirúrgica. Los objetivos de este trabajo son conocer las características generales de la patología para sistematizar el manejo logrando así un óptimo asesoramiento de los padres a nivel prenatal y seguimiento postnatal del recién nacido.

Congenital diaphragmatic hernia is a defect in the diaphragm that leads to herniation of theabdominal contents of the thoracic cavity during the intrauterine period. Morbidity and mortality are determined by the association with other malformations, the degree ofpulmonary hypoplasia and the presence of secondary pulmonary hypertension.It has an estimated incidence of 1 every 2,500-3,000 live newborns, and in 60% of the cases it is an isolated malformation. It is an evolutionary pathology that can be diagnosed from week 20-24; it is most commonly located in the left posterolateral. It is a pathology that requires intensive care at birth and after delivery and once the patient has been stabilized, surgical action is required. The objectives of this work are to understand the general characteristics of the pathology in order to refine its manipulation and achieve optimal counseling for parents at the newborn's prenatal and postnatal stages.

A hérnia diafragmática congênita é um defeito no diafragma que leva à herniação doconteúdo abdominal para a cavidade torácica durante o período intrauterino. A morbimortalidade é determinada pela associação com outras malformações, pelo grau de hipoplasia pulmonar e pela presença de hipertensão pulmonar secundária. Apresenta uma incidência estimada de 1 a cada 2.500-3.000 nascidos vivos, constituindo-se em 60% uma malformação isolada. É uma patologia evolutiva que pode ser diagnosticada a partir da semana 20-24 e a localização mais comum é o póstero-lateral esquerdo. É uma patologia que requer internação em terapia intensiva ao nascimento e após o parto. Uma vez que o paciente for estabilizado, é necessária ação cirúrgica. Os objetivos deste paper são conhecer as características gerais da patologia para melhorar o seu manejo, obtendo assim um aconselhamento ideal para os pais no nível pré-natal e no acompanhamento do crescimento pós-natal do recém-nascido.

A behavioral approach to annotating sleep in infants: Building on the classic framework.

In infants, monitoring and assessment of sleep can offer valuable insights into sleep problems and neuro-cognitive development. The gold standard for sleep measurements is polysomnography (PSG), but this is rather obtrusive, and unpractical in non-laboratory situations. Behavioral observations constitute a non-obtrusive, infant-friendly alternative. In the current methodological paper, we describe and validate a behavior-based framework for annotating infant sleep states. For development of the framework, we used existing sleep data from an in-home study with an unobtrusive test setup. Participants were 20 infants with a mean age of 180 days. Framework development was based on Prechtl's method. We added rules and guidelines based on discussions and consent among annotators. Key to using our framework is combining data from several modalities, for example, closely observing the frequency, type, and quality of movements, breaths, and sounds an infant makes, while taking the context into account. For a first validation of the framework, we set up a small study with 14 infants (mean age 171 days), in which they took their day-time nap in a laboratory setting. They were continuously monitored by means of PSG, as well as by the test setup from the in-home study. Recordings were annotated based both on PSG and our framework, and then compared. Data showed that for scoring wake vs. active sleep vs. quiet sleep the framework yields results comparable to PSG with a Cohen's Kappa agreement of ≥0.74. Future work with a larger cohort is necessary for further validating this framework, and with clinical populations for determining whether it can be generalized to these populations as well.

Continuous Glucose Monitoring in the Management of Neonates With Persistent Hypoglycemia and Congenital Hyperinsulinism.

BACKGROUND: Persistent hypoglycemia is common in the newborn and is associated with poor neurodevelopmental outcome. Adequate monitoring is critical in prevention, but is dependent on frequent, often hourly blood sampling. Continuous glucose monitoring (CGM) is increasingly being used in children with type 1 diabetes mellitus, but use in neonatology remains limited. We aimed to introduce real-time CGM to provide insights into patterns of dysglycemia and to support the management of persistent neonatal hypoglycemia. METHODS: This is a single-center retrospective study of real-time CGM use over a 4-year period in babies with persistent hypoglycemia. RESULTS: CGMs were inserted in 14 babies: 8 term and 6 preterm infants, 9 with evidence of congenital hyperinsulinism (CHI). A total of 224 days of data was collected demonstrating marked fluctuations in glucose levels in babies with CHI, with a higher sensor glucose SD (1.52 ±â€…0.79 mmol/L vs 0.77 ±â€…0.22 mmol/L) in infants with CHI compared with preterm infants. A total of 1254 paired glucose values (CGM and blood) were compared and gave a mean absolute relative difference of 11%. CONCLUSION: CGM highlighted the challenges of preventing hypoglycemia in these babies when using intermittent blood glucose levels alone, and the potential application of CGM as an adjunct to clinical care.

Standardization of reticulocyte counts in the athlete biological passport: A practical update.

INTRODUCTION: The athlete biological passport monitors blood variables over time to uncover blood doping. With the phasing in of a new series of blood analyzers, the Sysmex XN series, it was necessary to examine the comparability of results with the previously employed XT/XE series. A previous comparison between XN and XT/XE series suggested a small but significant bias between the two instruments in the measurements of RET%. Here, we examined the comparability of RET% on the XN and XT/XE platform using data collected over the first year since the transition. METHODS: The comparability of results obtained from XN and XT/XE instruments was assessed using three datasets: (i) 767 blood samples measured on both instrument series in 22 WADA-accredited laboratories, (ii) 27 323 samples measured on either instrument across 31 laboratories, and (iii) 119 clinical samples and 110 anti-doping samples measured on both instruments in a single laboratory. RESULTS: Analysis of the three datasets confirms the previous observation of a bias toward higher RET% values for samples measured on Sysmex XN instruments compared with the XT/XE series. Using data across a larger number of XN instruments and a larger athlete population, the current work suggests that the bias is proportional and slightly higher than previously observed across most of the range RET% values. CONCLUSION: A model is proposed for the comparison of data across XN and XT/XE technologies whereby the instrument bias increases proportionally with RET% measured on Sysmex XN Series, but where the rate of increase is negatively related to IRF%.

Patients with oral preneoplastic lesions and integration of dental pathology referrals.

PURPOSE: Oral cancers lack standardized monitoring systems. Our institution has developed an active surveillance system which provides detailed monitoring and follow up of patients with oral preneoplastic lesions (OPL). We examined a historic cohort of patients with OPL seen by regional dental professionals and a current cohort of clinic patients. The major aim was to examine follow up practices for biopsy proven dysplasia to gauge appropriateness of an active monitoring system for oral carcinoma. MATERIALS AND METHODS: Questionnaires regarding patients with OPL were sent to 285 dentists who had requested oral pathology services from our institution. The follow up practices of 141 dentists were evaluated for patients with OPL. We then examined our current clinic referral patterns for the number of dental referrals after the creation of an oral carcinoma active surveillance clinic. RESULTS: There were 76.5% (108/141) of patients who received follow up after diagnosis of preneoplastic oral lesions with 14.1% who underwent repeat biopsy. There was a malignant transformation rate of 11.3% including transformation of 42.8% of severe dysplasias into carcinoma within 2 years. After establishment of a dental referral clinic, 21.8% of tumor visits in a six-week period were referred from the regional dental community. CONCLUSIONS: A high rate of transformation of OPL to cancer in this cohort may support a role for joint dental and otolaryngology surveillance of dysplasia with longitudinal follow up.

Weakly Supervised Classification of Vital Sign Alerts as Real or Artifact.

A significant proportion of clinical physiologic monitoring alarms are false. This often leads to alarm fatigue in clinical personnel, inevitably compromising patient safety. To combat this issue, researchers have attempted to build Machine Learning (ML) models capable of accurately adjudicating Vital Sign (VS) alerts raised at the bedside of hemodynamically monitored patients as real or artifact. Previous studies have utilized supervised ML techniques that require substantial amounts of hand-labeled data. However, manually harvesting such data can be costly, time-consuming, and mundane, and is a key factor limiting the widespread adoption of ML in healthcare (HC). Instead, we explore the use of multiple, individually imperfect heuristics to automatically assign probabilistic labels to unlabeled training data using weak supervision. Our weakly supervised models perform competitively with traditional supervised techniques and require less involvement from domain experts, demonstrating their use as efficient and practical alternatives to supervised learning in HC applications of ML.

Ultra-conformal skin electrodes with synergistically enhanced conductivity for long-time and low-motion artifact epidermal electrophysiology.

Accurate and imperceptible monitoring of electrophysiological signals is of primary importance for wearable healthcare. Stiff and bulky pregelled electrodes are now commonly used in clinical diagnosis, causing severe discomfort to users for long-time using as well as artifact signals in motion. Here, we report a ~100 nm ultra-thin dry epidermal electrode that is able to conformably adhere to skin and accurately measure electrophysiological signals. It showed low sheet resistance (~24 Ω/sq, 4142 S/cm), high transparency, and mechano-electrical stability. The enhanced optoelectronic performance was due to the synergistic effect between graphene and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), which induced a high degree of molecular ordering on PEDOT and charge transfer on graphene by strong π-π interaction. Together with ultra-thin nature, this dry epidermal electrode is able to accurately monitor electrophysiological signals such as facial skin and brain activity with low-motion artifact, enabling human-machine interfacing and long-time mental/physical health monitoring.

Monitoring and modifying brain oxygenation in patients at risk of hypoxic ischaemic brain injury after cardiac arrest.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Importance of access to epilepsy monitoring units during the COVID-19 pandemic: Consensus statement of the International League against epilepsy and the International Federation of Clinical Neurophysiology.

Restructuring of healthcare services during the COVID-19 pandemic has led to lockdown of Epilepsy Monitoring Units (EMUs) in many hospitals. The ad-hoc taskforce of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) highlights the detrimental effect of postponing video-EEG monitoring of patients with epilepsy and other paroxysmal events. The taskforce calls for action to continue functioning of Epilepsy Monitoring Units during emergency situations, such as the COVID-19 pandemic. Long-term video-EEG monitoring is an essential diagnostic service. Access to video-EEG monitoring of the patients in the EMUs must be given high priority. Patients should be screened for COVID-19, before admission, according to the local regulations. Local policies for COVID-19 infection control should be adhered to during the video-EEG monitoring. In cases of differential diagnosis where reduction of antiseizure medication is not required, consider home video-EEG monitoring as an alternative in selected patients.

Automated pupillometry helps monitor the efficacy of cardiopulmonary resuscitation and predict return of spontaneous circulation.

BACKGROUND: We investigated the effectiveness of automated pupillometry on monitoring cardiopulmonary resuscitation (CPR) and predicting return of spontaneous circulation (ROSC) in a swine model of cardiac arrest (CA). METHODS: Sixteen male domestic pigs were included. Traditional indices including coronary perfusion pressure (CPP), end-tidal carbon dioxide (ETCO2), regional cerebral tissue oxygen saturation (rSO2) and carotid blood flow (CBF) were continuously monitored throughout the experiment. In addition, the pupillary parameters including the initial pupil size before constriction (Init, maximum diameter), the end pupil size at peak constriction (End, minimum diameter), and percentage of change (%PLR) were measured by an automated quantitative pupillometer at baseline, at 1, 4, 7 min during CA, and at 1, 4, 7 min during CPR. RESULTS: ROSC was achieved in 11/16 animals. The levels of CPP, ETCO2, rSO2 and CBF were significantly greater during CPR in resuscitated animals than those non-resuscitated ones. Init and End were decreased and %PLR was increased during CPR in resuscitated animals when compared with those non-resuscitated ones. There were moderate to good significant correlations between traditional indices and Init, End, and %PLR (|r| = 0.46-0.78, all P < 0.001). Furthermore, comparable performance was also achieved by automated pupillometry (AUCs of Init, End and %PLR were 0.821, 0.873 and 0.821, respectively, all P < 0.05) compared with the traditional indices (AUCs = 0.809-0.946). CONCLUSION: The automated pupillometry may serve as an effective surrogate method to monitor cardiopulmonary resuscitation efficacy and predict ROSC in a swine model of cardiac arrest.

Reliability of GENEActiv accelerometers to estimate sleep, physical activity, and sedentary time in children.

BACKGROUND: Reliable estimates of habitual sleep, physical activity, and sedentary time are essential to investigate the associations between these behaviours and health outcomes. While the number of days needed and hours/day for estimates of physical activity and sedentary time are generally known, the criteria for sleep estimates are more uncertain. The objective of this study was to identify the number of nights needed to obtain reliable estimates of habitual sleep behaviour using the GENEActiv wrist worn accelerometer. The number of days to obtain reliable estimate of physical activity was also examined. METHODS: Data was used from a two-year longitudinal study. Children wore an accelerometer for up to 8 days 24 h/day across three timepoints. The sample included 2,745 children (51 % girls) between the ages of 7-12-years-old (mean = 9.8 years, SD = 1.1 year) with valid accelerometer data from any timepoint. Reliability estimates were calculated for sleep duration, sleep efficiency, sleep onset, wake time, time in bed, light physical activity, moderate physical activity, moderate-to-vigorous physical activity, vigorous physical activity, and sedentary time. RESULTS: Intraclass correlations and the Spearman Brown prophecy formula were used to determine the nights and days needed for reliable estimates. We found that between 3 and 5 nights were needed to achieve acceptable reliability (ICC = 0.7) in sleep outcomes, while physical activity and sedentary time outcomes required between 3 and 4 days. CONCLUSIONS: To obtain reliable estimates, researchers should consider these minimum criteria when designing their studies and prepare strategies to ensure sufficient wear time compliance.

How to implement a PEWS in a resource-limited setting: A quantitative analysis of the bedside-PEWS implementation in a hospital in northeast Brazil.

OBJECTIVES: Quantitative analysis of the implementation of the bedside paediatric early warning system (B-PEWS) in a resource-limited setting. The B-PEWS serves to pre-emptively identify hospitalised children who are at risk for cardiopulmonary arrest and subsequently to provide critical care in time. METHODS: We performed a retrospective review through the medical data records of patients after discharge from the paediatric ward of a philanthropic hospital in Brazil. Nurses' performance using the system was measured with various parameters. RESULTS: A total of 499 patients were included, and a total of 8024 scores were checked. During the 21-week research period, the implementation rate increased significantly from 66.5% (SD 26.0) in Period 1 to 93.1% (SD 16.6) in Period 2. The number of scores that resulted in a correct total score went from 7.5% in Period 1 to 32.2% in Period 2, p < 0.001. There was an improvement in the correct choice of age group between the two periods (from 32.2% to 53.4%). There was no difference in the mean admission time of patients in the two periods: in the first period 4.8 days (SD 2.9) and in the second period 4.8 days (SD 4.1). CONCLUSIONS: It is possible to implement a PEWS in resource-limited settings while achieving high implementation rates. However, this is a time- and energy-consuming process. Having an active and involved team that is responsible for implementation is key for a successful implementation. Factors that likely hindered implementation were a large change in workflow for the nursing staff, non-native speakers as main investigators.

Recommendations for standards of monitoring during anaesthesia and recovery 2021: Guideline from the Association of Anaesthetists.

This guideline updates and replaces the 5th edition of the Standards of Monitoring published in 2015. The aim of this document is to provide guidance on the minimum standards for monitoring of any patient undergoing anaesthesia or sedation under the care of an anaesthetist. The recommendations are primarily aimed at anaesthetists practising in the UK and Ireland, but it is recognised that these guidelines may also be of use in other areas of the world. Minimum standards for monitoring patients during anaesthesia and in the recovery phase are included. There is also guidance on monitoring patients undergoing sedation and during transfer. There are new sections specifically discussing capnography, sedation and regional anaesthesia. In addition, the indications for processed electroencephalogram and neuromuscular monitoring have been updated.

International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers.

Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.