An Innovative Telemedical Network to Improve Infectious Disease Management in Critically Ill Patients and Outpatients (TELnet@NRW): Stepped-Wedge Cluster Randomized Controlled Trial.

BACKGROUND: Evidence-based infectious disease and intensive care management is more relevant than ever. Medical expertise in the two disciplines is often geographically limited to university institutions. In addition, the interconnection between inpatient and outpatient care is often insufficient (eg, no shared electronic health record and no digital transfer of patient findings). OBJECTIVE: This study aims to establish and evaluate a telemedical inpatient-outpatient network based on expert teleconsultations to increase treatment quality in intensive care medicine and infectious diseases. METHODS: We performed a multicenter, stepped-wedge cluster randomized trial (February 2017 to January 2020) to establish a telemedicine inpatient-outpatient network among university hospitals, hospitals, and outpatient physicians in North Rhine-Westphalia, Germany. Patients aged ≥18 years in the intensive care unit or consulting with a physician in the outpatient setting were eligible. We provided expert knowledge from intensivists and infectious disease specialists through advanced training courses and expert teleconsultations with 24/7/365 availability on demand respectively once per week to enhance treatment quality. The primary outcome was adherence to the 10 Choosing Wisely recommendations for infectious disease management. Guideline adherence was analyzed using binary logistic regression models. RESULTS: Overall, 159,424 patients (10,585 inpatients and 148,839 outpatients) from 17 hospitals and 103 outpatient physicians were included. There was a significant increase in guideline adherence in the management of Staphylococcus aureus infections (odds ratio [OR] 4.00, 95% CI 1.83-9.20; P<.001) and in sepsis management in critically ill patients (OR 6.82, 95% CI 1.27-56.61; P=.04). There was a statistically nonsignificant decrease in sepsis-related mortality from 29% (19/66) in the control group to 23.8% (50/210) in the intervention group. Furthermore, the extension of treatment with prophylactic antibiotics after surgery was significantly less likely (OR 9.37, 95% CI 1.52-111.47; P=.04). Patients treated by outpatient physicians, who were regularly participating in expert teleconsultations, were also more likely to be treated according to guideline recommendations regarding antibiotic therapy for uncomplicated upper respiratory tract infections (OR 1.34, 95% CI 1.16-1.56; P<.001) and asymptomatic bacteriuria (OR 9.31, 95% CI 3.79-25.94; P<.001). For the other recommendations, we found no significant effects, or we had too few observations to generate models. The key limitations of our study include selection effects due to the applied on-site triage of patients as well as the limited possibilities to control for secular effects. CONCLUSIONS: Telemedicine facilitates a direct round-the-clock interaction over broad distances between intensivists or infectious disease experts and physicians who care for patients in hospitals without ready access to these experts. Expert teleconsultations increase guideline adherence and treatment quality in infectious disease and intensive care management, creating added value for critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03137589; https://clinicaltrials.gov/ct2/show/NCT03137589.

Additional Telemedicine Rounds as a Successful Performance-Improvement Strategy for Sepsis Management: Observational Multicenter Study.

BACKGROUND: Sepsis is a major health care problem with high morbidity and mortality rates and affects millions of patients. Telemedicine, defined as the exchange of medical information via electronic communication, improves the outcome of patients with sepsis and decreases the mortality rate and length of stay in the intensive care unit (ICU). Additional telemedicine rounds could be an effective component of performance-improvement programs for sepsis, especially in underserved rural areas and hospitals without ready access to critical care physicians. OBJECTIVE: Our aim was to evaluate the impact of additional daily telemedicine rounds on adherence to sepsis bundles. We hypothesized that additional telemedicine support may increase adherence to sepsis guidelines and improve the detection rates of sepsis and septic shock. METHODS: We conducted a retrospective, observational, multicenter study between January 2014 and July 2015 with one tele-ICU center and three ICUs in Germany. We implemented telemedicine as part of standard care and collected data continuously during the study. During the daily telemedicine rounds, routine screening for sepsis was conducted and adherence to the Surviving Sepsis Campaign's 3-hour and 6-hour sepsis bundles were evaluated. RESULTS: In total, 1168 patients were included in this study, of which 196 were positive for severe sepsis and septic shock. We found that additional telemedicine rounds improved adherence to the 3-hour (Quarter 1, 35% vs Quarter 6, 76.2%; P=.01) and 6-hour (Quarter 1, 50% vs Quarter 6, 95.2%; P=.001) sepsis bundles. In addition, we noted an increase in adherence to the item "Administration of fluids when hypotension" (Quarter 1, 80% vs Quarter 6, 100%; P=.049) of the 3-hour bundle and the item "Remeasurement of lactate" (Quarter 1, 65% vs Quarter 6, 100%, P=.003) of the 6-hour bundle. The ICU length of stay after diagnosis of severe sepsis and septic shock remained unchanged over the observation period. Due to a higher number of patients with sepsis in Quarter 5 (N=60) than in other quarters, we observed stronger effects of the additional rounds on mortality in this quarter (Quarter 1, 50% vs Quarter 5, 23.33%, P=.046). CONCLUSIONS: Additional telemedicine rounds are an effective component of and should be included in performance-improvement programs for sepsis management.

Telemedizin: Chancen und Grenzen in der Intensivmedizin.

Intensive care unit (ICU) telemedicine is one option to improve clinical relevant outcomes in terms of mortality, length of stay and morbidity. Telemedicine combines the advantage of locally available intensive medical care with the shared expertise of specialized centers by data and information exchange. The article describes the organizational and technical feasibility of different options, as well as the effects and limitations of ICU telemedicine.

[Tele-cooperation for innovative care using the example of the University Hospital Aachen. Telematics in intensive care medicine, emergency medicine, and telemedical intersectoral rehabilitation planning in geriatric trauma]. / Telekooperation für die innovative Versorgung am Beispiel des Universitätsklinikums Aachen : Telematik in der Intensivmedizin (TIM), Telenotarzt und Telemedizinische intersektorale Rehabilitationsplanung in der Alterstraumatologie (TIRA).

The demographic challenge of the ageing society is associated with increasing comorbidity. On the other hand, there will be an ageing workforce in medicine, resulting in an imbalance between the demand and supply of medical care in the near future. In rural areas in particular, this imbalance is already present today. Based on three best practice projects carried out by our telemedical center in Aachen, including emergency medicine, intensive care medicine, and the rehabilitation planning of geriatric trauma care, some experience and the potential of the intersectoral provision of care, supported by telemedicine, are demonstrated. Telemedicine is the provision of medical services over a geographical distance by using tele-communication and data transfer. It has been proven to ensure a constant quality of health care. Telemedical support enables shared expertise independent of time and space, and allows efficient allocation of resources. A review of international experience supports this notion.

[Surgical therapy and critical care medicine in severely burned patients - Part 2: the basics in definite care]. / Operative Therapie und Intensivmedizin bei Schwerbrandverletzten - Teil 2: Grundzüge der Weiterversorgung.

Critical care medicine in severely burned patients should be adapted to the different pathophysiological phases. Accordingly, surgical and non-surgical therapy must be coordinated adequately. Initial stabilization of the burn victim during the first 24 hours (Surgical therapy and critical care medicine in severely burned patients - Part 1: the first 24 ours, AINS 9/12) is followed by a long lasting reconstructive period. During this time calculated fluid replacement to compensate evaporative losses by large bourn wounds is as essential as reconstruction of the integrity of the skin and the modulation of metabolic consequences following severe burn injury. Special attention has to be paid to local and systemic infections.

[Surgical therapy and critical care medicine in severely burned patients - Part 1: the first 24 ours]. / Operative Therapie und Intensivmedizin bei Schwerbrandverletzten - Teil 1: die ersten 24 Stunden.

Critical care medicine in severely burned patients should be adapted to the different pathophysiological phases. Accordingly, surgical and non-surgical therapy must be coordinated adequately. Initial wound care comprises topical treatment of less severely injured skin and surgical debridement of severely burned areas. The first 24 hours of intensive care are focused on calculated fluid delivery to provide stable hemodynamics and avoid progression of local edema formation. In the further course wound treatment with split-thickness skin grafts is the major aim of surgical therapy. Critical care is focused on the avoidance of complications like infections and ventilator associated lung injury. Therefore, lung-protective ventilation strategies, weaning and sedation protocols, and early enteral nutrition are important cornerstones of the treatment.

Medication safety in a German telemedicine centre: Implementation of a telepharmaceutical expert consultation in addition to existing tele-intensive care unit services.

Introduction: Tele-intensive care unit (tele-ICU) services offer the possibility to provide specialized medical care in remote areas and to improve patient outcomes. The aim of this study was to implement and evaluate an additional telepharmaceutical expert consultation as part of tele-ICU services. Methods: This is a prospective observational study conducted in the telemedicine centre of the University Hospital RWTH Aachen, Germany. Between March and July 2015, all tele-ICU patients of one internal and two remote ICUs received telepharmaceutical consultation. Number and type of drug related problems (DRPs) were identified in a comprehensive medication safety check. Implementation of DRPs was discussed interdisciplinarily by tele-ICU pharmacist, tele-ICU physician and remote ICU physician. Special focus was on drug­drug interactions (DDIs) and dosage adjustment in renal and liver failure. Results: A total of 210 DRPs in 103 patients were identified and discussed. On average, 2.0 (range 0­17) DRPs per patient were found. At least one DRP was found in 62% of patients. Antibacterials for systemic use were most involved in DRPs. A total of 1129 DDI-alerts were generated by ID PHARMA CHECK®. Fifty-six DDIs (5%) were discussed in tele-ICU rounds. The tele-ICU team discussed 28 cases of dosage adjustment in organ failure. Discussion: Telepharmaceutical consultation as part of tele-ICU services was successfully implemented and can improve medication safety. Telemedicine infrastructure provides the possibility to implement guidelines recommending pharmaceutical service in the ICU in remote hospitals not having access to clinical pharmacists. Thus, quality of care can be improved.

Critical Transitions in Intensive Care Units: A Sepsis Case Study.

The progression of complex human diseases is associated with critical transitions across dynamical regimes. These transitions often spawn early-warning signals and provide insights into the underlying disease-driving mechanisms. In this paper, we propose a computational method based on surprise loss (SL) to discover data-driven indicators of such transitions in a multivariate time series dataset of septic shock and non-sepsis patient cohorts (MIMIC-III database). The core idea of SL is to train a mathematical model on time series in an unsupervised fashion and to quantify the deterioration of the model's forecast (out-of-sample) performance relative to its past (in-sample) performance. Considering the highest value of the moving average of SL as a critical transition, our retrospective analysis revealed that critical transitions occurred at a median of over 35 hours before the onset of septic shock, which suggests the applicability of our method as an early-warning indicator. Furthermore, we show that clinical variables at critical-transition regions are significantly different between septic shock and non-sepsis cohorts. Therefore, our paper contributes a critical-transition-based data-sampling strategy that can be utilized for further analysis, such as patient classification. Moreover, our method outperformed other indicators of critical transition in complex systems, such as temporal autocorrelation and variance.

Fluid therapy and outcome: a prospective observational study in 65 German intensive care units between 2010 and 2011.

BACKGROUND: Outcome data on fluid therapy in critically ill patients from randomised controlled trials may be different from data obtained by observational studies under "real-life" conditions. We conducted this prospective, observational study to investigate current practice of fluid therapy (crystalloids and colloids) and associated outcomes in 65 German intensive care units (ICUs). In total, 4545 adult patients who underwent intravenous fluid therapy were included. The main outcome measures were 90-day mortality, ICU mortality and acute kidney injury (AKI). Data were analysed using logistic and Cox regression models, as appropriate. RESULTS: In the predominantly post-operative overall cohort, unadjusted 90-day mortality was 20.1%. Patients who also received colloids (54.6%) had a higher median Simplified Acute Physiology Score II [25 (interquartile range 11; 41) vs. 17 (7; 31)] and incidence of severe sepsis (10.2 vs. 7.4%) on admission compared to patients who received exclusively crystalloids (45.4%). 6% hydroxyethyl starch (HES 130/0.4) was the most common colloid (57.0%). Crude rates of 90-day mortality were higher for patients who received colloids (OR 1.845 [1.560; 2.181]). After adjustment for baseline variables, the HR was 1.666 [1.405; 1.976] and further decreased to indicate no associated risk (HR 1.003 [0.980; 1.027]) when it was adjusted for vasopressor use, severity of disease and transfusions. Similarly, the crude risk of AKI was higher in the colloid group (crude OR 3.056 [2.528; 3.694]), after adjustment for baseline variables OR 1.941 [1.573; 2.397], and after full adjustment OR 0.696 [0.629; 0.770]), the risk of AKI turned out to be reduced. The same was true for the subgroup of patients treated with 6% HES 130/0.4 (crude OR 1.931 [1.541; 2.419], adjusted for baseline variables OR 2.260 [1.730; 2.953] and fully adjusted OR 0.800 [0.704; 0.910]) as compared to crystalloids only. CONCLUSIONS: The present analysis of mostly post-operative patients in routine clinical care did not reveal an independent negative effect of colloids (mostly 6% HES 130/0.4) on renal function or survival after multivariable adjustment. Signals towards a reduced risk in subgroup analyses deserve further study. Trial registration ClinicalTrials.gov Identifier: NCT01122277, registered May 11th, 2010.

Interleukin-6 Serum Levels Correlate With Severity of Burn Injury but Not With Gender.

Gender-specific differences in the outcome of patients with burn injury have been recognized in the past with female patients being at a higher risk of mortality. We hypothesized that early post-burn interleukin-6 (IL-6) cytokine levels may contribute to the different gender-specific outcome. We retrospectively examined 94 burned patients who were treated in the Burn Intensive Care Unit at the University Hospital Aachen. Age, gender, presence of inhalation injury, depth, TBSA, and clinical outcome were documented. Serum samples for IL-6 analysis were collected within 24 hours posttrauma. The relationship between IL-6 levels, gender, survival, and abbreviated burn severity index score was investigated. Male patients (64.9%; n = 61) presented a higher median TBSA (26%) than female patients (20%). The mortality rate of male patients (27.9%; n = 17) and female patients (21.2%; n = 7) was similar. Deceased patients had significant higher TBSA (P = 0.0005) and IL-6 levels (P = 0.0007) than burn survivors. A moderate correlation between IL-6 levels and abbreviated burn severity index score was observed (r = 0.554; P < 0.0001). While TBSA showed a significant influence on IL-6 levels (P = 0.0003), gender did not (P = 0.7395) and inhalation injury indicated a minor influence (P = 0.0780). Only TBSA and age presented a significant influence on mortality (P = 0.0028 and P = 0.0031, respectively). All patients with burn trauma were characterized by elevated IL-6 levels with higher TBSA values resulting in more pronounced levels. Deceased patients had higher initial IL-6 serum levels reflecting higher TBSA and severity. In contrast to other defined trauma mechanisms, gender had no significant influence on postburn IL-6 serum levels and mortality in our patient population.

Binding of urokinase-type plasminogen activator receptor (uPAR) to the mannose 6-phosphate/insulin-like growth factor II receptor: contrasting interactions of full-length and soluble forms of uPAR.

Urokinase-type plasminogen activator receptor (uPAR) binding by the mannose 6-phosphate/insulin-like growth factor II receptor (Man-6-P/IGF2R) is considered important to Man-6-P/IGF2R tumor suppressor function via regulation of cell surface proteolytic activity. Our goal was to map the uPAR binding site of the Man-6-P/IGF2R by analyzing the uPAR binding characteristics of a panel of minireceptors containing different regions of the Man-6-P/IGF2R extracytoplasmic domain. Coimmunoprecipitation assays revealed that soluble recombinant uPAR (suPAR) bound the Man-6-P/IGF2R at two distinct sites, one localized to the amino-terminal end of the Man-6-P/IGF2R extracytoplasmic domain (repeats 1-3) and the other to the more carboxyl-terminal end (repeats 7-9). These sites correspond with the positions of the two Man-6-P binding domains of Man-6-P/IGF2R. Indeed, the suPAR-Man-6-P/IGF2R interaction was inhibited by Man-6-P, and binding-competent su-PAR species represented a minor percentage (8-30%) of the suPAR present. In contrast, Man-6-P/IGF2R binding of endogenous, full-length uPAR solubilized from plasma membranes of the prostate cancer cell line, PC-3, was not inhibited by Man-6-P. Further studies showed that very little (<5%) endogenous uPAR was Man-6-P/IGF2R binding-competent. We conclude that, contrary to previous reports, the interaction between uPAR and Man-6-P/IGF2R is a low percentage binding event and that suPAR and full-length uPAR bind the Man-6-P/IGF2R by different mechanisms.