Telemedicine in Intensive Care Units: Protocol for a Scoping Review

Background: Telemedicine has been deployed to address issues in intensive care delivery, as well as to improve outcome and quality of care. Implementation of this technology has been characterized by high variability. Tele-intensive care unit (ICU) interventions involve the combination of multiple technological and organizational components, as well as interconnections of key stakeholders inside the hospital organization. The extensive literature on the benefits of tele-ICUs has been characterized as heterogeneous. On one hand, positive clinical and economical outcomes have been shown in multiple studies. On the other hand, no tangible benefits could be detected in several cases. This could be due to the diverse forms of organizations and the fact that tele-ICU interventions are complex to evaluate. The implementation context of tele-ICUs has been shown to play an important role in the success of the technology. The benefits derived from tele-ICUs depend on the organization where it is deployed and how the telemedicine systems are applied. There is therefore value in analyzing the benefits of tele-ICUs in relation to the characteristics of the organization where it is deployed. To date, research on the topic has not provided a comprehensive overview of literature taking both the technology setup and implementation context into account. Objective: We present a protocol for a scoping review of the literature on telemedicine in the ICU and its benefits in intensive care. The purpose of this review is to map out evidence about telemedicine in critical care in light of the implementation context. This review could represent a valuable contribution to support the development of tele-ICU technologies and offer perspectives on possible configurations, based on the implementation context and use case. Methods: We have followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist and the recommendations of the Joanna Briggs Institute methodology for scoping reviews. The scoping review and subsequent systematic review will be completed by spring 2021. Results: The preliminary search has been conducted. After removing all duplicates, we found 2530 results. The review can now be advanced to the next steps of the methodology, including literature database queries with appropriate keywords, retrieval of the results in a reference management tool, and screening of titles and abstracts. Conclusions: The results of the search indicate that there is sufficient literature to complete the scoping review. Upon completion, the scoping review will provide a map of existing evidence on tele-ICU systems given the implementation context. Findings of this research could be used by researchers, clinicians, and implementation teams as they determine the appropriate setup of new or existing tele-ICU systems. The need for future research contributions and systematic reviews will be identified. International Registered Report Identifier (IRRID): DERR1-10.2196/1969

Case Report Intravenous Lormetazepam during Sedation Weaning in a 26-Year-Old Critically Ill Woman

Recent evidence revealed that sedation is related to adverse outcomes including a higher mortality. Despite this fact, patients sometimes require deep sedation for a limited period of time to control, for example, intracranial hypertension. In particular in these cases, weaning from sedation is often challenging due to emerging agitation, stress, and delirium. The submitted research letter reports a rare case of severe and persisting agitation that was unresponsive to all available treatments. Ultimately, lormetazepam which has recently become available for intravenous use in Germany resolved the problem by stress-reduction and anxiolysis without leading to measurable sedation

METHOD EVALUATION TO DETERMINE HYDRATION STATES OF TENDONS BY USING MRI

Due to the fact that water content is a determinant of the material properties of tendons and therefore might affect sports performance and the risk of injury, the purpose of this pilot study was to evaluate the reliabilityand sensitivity of a MRI based method to quantify content of a tendon. For this pilot study twenty porcine digital flexor tendons were chosen. All samples were examined on a MR scanner using three 3D ultra-short echo time sequences. With the applied sequences it was possible to determine a decrease in water content of the tendons. In addition, the methods showed a good inter session reliability. Further investigations are needed to improve the upper and lower limit of resolution regarding the physiological hydration state

evaluating a novel online depression intervention for persons with epilepsy

Background Depression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet- administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual. Methods/Design This randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3). Discussion Results of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety. Trial registration ClinicalTrials.gov: NCT02791724. Registered 01 June 2016

Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support

Background Extracorporeal membrane oxygenation (ECMO) or pumpless extracorporeal lung assist (pECLA) requires effective anticoagulation. Knowledge on the use of argatroban in patients with acute respiratory distress syndrome (ARDS) undergoing ECMO or pECLA is limited. Therefore, this study assessed the feasibility, efficacy and safety of argatroban in critically ill ARDS patients undergoing extracorporeal lung support. Methods This retrospective analysis included ARDS patients on extracorporeal lung support who received argatroban between 2007 and 2014 in a single ARDS referral center. As controls, patients who received heparin were matched for age, sex, body mass index and severity of illness scores. Major and minor bleeding complications, thromboembolic events, administered number of erythrocyte concentrates, thrombocytes and fresh-frozen plasmas were assessed. The number of extracorporeal circuit systems and extracorporeal lung support cannulas needed due to clotting was recorded. Also assessed was the efficacy to reach the targeted activated partial thromboplastin time (aPTT) in the first consecutive 14 days of therapy, and the controllability of aPTT values is within a therapeutic range of 50–75 s. Fisher’s exact test, Mann–Whitney U tests, Friedman tests and multivariate nonparametric analyses for longitudinal data (MANOVA; Brunner’s analysis) were applied where appropriate. Results Of the 535 patients who met the inclusion criteria, 39 receiving argatroban and 39 matched patients receiving heparin (controls) were included. Baseline characteristics were similar between the two groups, including severity of illness and organ failure scores. There were no significant differences in major and minor bleeding complications. Rates of thromboembolic events were generally low and were similar between the two groups, as were the rates of transfusions required and device-associated complications. The controllability of both argatroban and heparin improved over time, with a significantly increasing probability to reach the targeted aPTT corridor over the first days (p < 0.001). Over time, there were significantly fewer aPTT values below the targeted aPTT goal in the argatroban group than in the heparin group (p < 0.05). Both argatroban and heparin reached therapeutic aPTT values for adequate application of extracorporeal lung support. Conclusions Argatroban appears to be a feasible, effective and safe anticoagulant for critically ill ARDS patients undergoing extracorporeal lung support

FUNC: a package for detecting significant associations between gene sets and ontological annotations

BACKGROUND: Genome-wide expression, sequence and association studies typically yield large sets of gene candidates, which must then be further analysed and interpreted. Information about these genes is increasingly being captured and organized in ontologies, such as the Gene Ontology. Relationships between the gene sets identified by experimental methods and biological knowledge can be made explicit and used in the interpretation of results. However, it is often difficult to assess the statistical significance of such analyses since many inter-dependent categories are tested simultaneously. RESULTS: We developed the program package FUNC that includes and expands on currently available methods to identify significant associations between gene sets and ontological annotations. Implemented are several tests in particular well suited for genome wide sequence comparisons, estimates of the family-wise error rate, the false discovery rate, a sensitive estimator of the global significance of the results and an algorithm to reduce the complexity of the results. CONCLUSION: FUNC is a versatile and useful tool for the analysis of genome-wide data. It is freely available under the GPL license and also accessible via a web service

Enhanced Recovery after Intensive Care (ERIC): study protocol for a German stepped wedge cluster randomised controlled trial to evaluate the effectiveness of a critical care telehealth program on process quality and functional outcome

Introduction: Survival after critical illness has noticeably improved over the last decades due to advances in critical care medicine. Besides, there is an increasing number of elderly patients with chronic diseases being treated in the intensive care unit (ICU). More than half of the survivors of critical illness suffer from medium-term or long-term cognitive, psychological and/or physical impairments after ICU discharge, which is recognised as post-intensive care syndrome (PICS). There are evidence-based and consensus-based quality indicators (QIs) in intensive care medicine, which have a positive influence on patients' long-term outcomes if adhered to. Methods and analysis: The protocol of a multicentre, pragmatic, stepped wedge cluster randomised controlled, quality improvement trial is presented. During 3 predefined steps, 12 academic hospitals in Berlin and Brandenburg, Germany, are randomly selected to move in a one-way crossover from the control to the intervention condition. After a multifactorial training programme on QIs and clinical outcomes for site personnel, ICUs will receive an adapted, interprofessional protocol for a complex telehealth intervention comprising of daily telemedical rounds at ICU. The targeted sample size is 1431 patients. The primary objective of this trial is to evaluate the effectiveness of the intervention on the adherence to eight QIs daily measured during the patient's ICU stay, compared with standard of care. Furthermore, the impact on long-term recovery such as PICS-related, patient-centred outcomes including health-related quality of life, mental health, clinical assessments of cognition and physical function, all-cause mortality and cost-effectiveness 3 and 6 months after ICU discharge will be evaluated. Ethics and dissemination: This protocol was approved by the ethics committee of the Charité-Universitätsmedizin, Berlin, Germany (EA1/006/18). The results will be published in a peer-reviewed scientific journal and presented at international conferences. Study findings will also be disseminated via the website (www.eric-projekt.net). Trial registration number: ClinicalTrials.gov Registry (NCT03671447)

Routine management of postoperative delirium outside the ICU: Results of an international survey among anaesthesiologists

Background: Postoperative delirium (POD) is a severe brain dysfunction. Although data indicate a high relevance, no survey has investigated the routine practice to monitor delirium outside the ICU setting after surgery. Prior to publishing of the new European Society of Anaesthesiology (ESA) guidelines on POD, an international survey was conducted to assess current practice. Methods: European Society of Anaesthesiology-endorsed online survey; Trial Registration: NCT-identifier: 02513537. Results: In total, 566 respondents from 62 countries accessed, and 564 (99.6%) completed the survey (completion rate). Overall, 385 (68%) of the respondents reported that delirium is either "very relevant" or "relevant" for their daily clinical practice. In all, 38 (7%) of the respondents routinely monitor for delirium in >50% of all patients. Asked on the monitoring time point, more than half (n = 308, 55%) indicated to screen before or at recovery room discharge, 235 (42%) up to the first postoperative day, 143 (25%) up to 3 days, and 77 (14%) up to 5 postoperative days. Although there is a lack of long-term monitoring, nearly all respondents (n = 530, 94%) reported to treat delirium. Availability of EEG/EMG-based monitoring to assess the depth of anaesthesia was high in the study group (n = 547, 97%) and was used by more than one-third of the respondents to reduce risk of burst suppression (n = 189, 34%). Conclusion: Although delirium is perceived as a relevant condition among anaesthesiologists, there is a high demand for implementing monitoring strategies after publishing of the POD Guideline. The survey shows that tools necessary for POD Guideline implementation are available in the centres represented by the respondents

K2-66b and K2-106b: Two Extremely Hot Sub-Neptune-size Planets with High Densities

We report precise mass and density measurements of two extremely hot sub-Neptune-size planets from the K2 mission using radial velocities, K2 photometry, and adaptive optics imaging. K2-66 harbors a close-in sub-Neptune-sized (2.49_(-0.24)^(+0.34)R_⊕) planet (K2-66b) with a mass of 21.3 ± 3.6 M_⊕. Because the star is evolving up the subgiant branch, K2-66b receives a high level of irradiation, roughly twice the main-sequence value. K2-66b may reside within the so-called "photoevaporation desert," a domain of planet size and incident flux that is almost completely devoid of planets. Its mass and radius imply that K2-66b has, at most, a meager envelope fraction (<5%) and perhaps no envelope at all, making it one of the largest planets without a significant envelope. K2-106 hosts an ultra-short-period planet (P = 13.7 hr) that is one of the hottest sub-Neptune-size planets discovered to date. Its radius (1.82_(-0.14)^(+0.20) R_⊕) and mass (9.0 ± 1.6 M_⊕) are consistent with a rocky composition, as are all other small ultra-short-period planets with well-measured masses. K2-106 also hosts a larger, longer-period planet (R_p = 2.77_(-0.23^(+0.37)R_⊕, P = 13.3 days) with a mass less than 24.4 M_⊕ at 99.7% confidence. K2-66b and K2-106b probe planetary physics in extreme radiation environments. Their high densities reflect the challenge of retaining a substantial gas envelope in such extreme environments

Proteome Sampling by the HLA Class I Antigen Processing Pathway

The peptide repertoire that is presented by the set of HLA class I molecules of an individual is formed by the different players of the antigen processing pathway and the stringent binding environment of the HLA class I molecules. Peptide elution studies have shown that only a subset of the human proteome is sampled by the antigen processing machinery and represented on the cell surface. In our study, we quantified the role of each factor relevant in shaping the HLA class I peptide repertoire by combining peptide elution data, in silico predictions of antigen processing and presentation, and data on gene expression and protein abundance. Our results indicate that gene expression level, protein abundance, and rate of potential binding peptides per protein have a clear impact on sampling probability. Furthermore, once a protein is available for the antigen processing machinery in sufficient amounts, C-terminal processing efficiency and binding affinity to the HLA class I molecule determine the identity of the presented peptides. Having studied the impact of each of these factors separately, we subsequently combined all factors in a logistic regression model in order to quantify their relative impact. This model demonstrated the superiority of protein abundance over gene expression level in predicting sampling probability. Being able to discriminate between sampled and non-sampled proteins to a significant degree, our approach can potentially be used to predict the sampling probability of self proteins and of pathogen-derived proteins, which is of importance for the identification of autoimmune antigens and vaccination targets