Continuous monitoring of physiological data using the patient vital status fusion score in septic critical care patients.

Accurate and standardized methods for assessing the vital status of patients are crucial for patient care and scientific research. This study introduces the Patient Vital Status (PVS), which quantifies and contextualizes a patient's physical status based on continuous variables such as vital signs and deviations from age-dependent normative values. The vital signs, heart rate, oxygen saturation, respiratory rate, mean arterial blood pressure, and temperature were selected as input to the PVS pipeline. The method was applied to 70 pediatric patients in the intensive care unit (ICU), and its efficacy was evaluated by matching high values with septic events at different time points in patient care. Septic events included systemic inflammatory response syndrome (SIRS) and suspected or proven sepsis. The comparison of maximum PVS values between the presence and absence of a septic event showed significant differences (SIRS/No SIRS: p < 0.0001, η2 = 0.54; Suspected Sepsis/No Suspected Sepsis: p = 0.00047, η2 = 0.43; Proven Sepsis/No Proven Sepsis: p = 0.0055, η2 = 0.34). A further comparison between the most severe PVS in septic patients with the PVS at ICU discharge showed even higher effect sizes (SIRS: p < 0.0001, η2 = 0.8; Suspected Sepsis: p < 0.0001, η2 = 0.8; Proven Sepsis: p = 0.002, η2 = 0.84). The PVS is emerging as a data-driven tool with the potential to assess a patient's vital status in the ICU objectively. Despite real-world data challenges and potential annotation biases, it shows promise for monitoring disease progression and treatment responses. Its adaptability to different disease markers and reliance on age-dependent reference values further broaden its application possibilities. Real-time implementation of PVS in personalized patient monitoring may be a promising way to improve critical care. However, PVS requires further research and external validation to realize its true potential.

Bilateral lung transplantation for pediatric pulmonary arterial hypertension: perioperative management and one-year follow-up.

Background: Bilateral lung transplantation (LuTx) remains the only established treatment for children with end-stage pulmonary arterial hypertension (PAH). Although PAH is the second most common indication for LuTx, little is known about optimal perioperative management and midterm clinical outcomes. Methods: Prospective observational study on consecutive children with PAH who underwent LuTx with scheduled postoperative VA-ECMO support at Hannover Medical School from December 2013 to June 2020. Results: Twelve patients with PAH underwent LuTx (mean age 11.9 years; age range 1.9-17.8). Underlying diagnoses included idiopathic (n = 4) or heritable PAH (n = 4), PAH associated with congenital heart disease (n = 2), pulmonary veno-occlusive disease (n = 1), and pulmonary capillary hemangiomatosis (n = 1). The mean waiting time was 58.5 days (range 1-220d). Three patients were bridged to LuTx on VA-ECMO. Intraoperative VA-ECMO/cardiopulmonary bypass was applied and VA-ECMO was continued postoperatively in all patients (mean ECMO-duration 185 h; range 73-363 h; early extubation). The median postoperative ventilation time was 28 h (range 17-145 h). Echocardiographic conventional and strain analysis showed that 12 months after LuTx, all patients had normal biventricular systolic function. All PAH patients are alive 2 years after LuTx (median follow-up 53 months, range 26-104 months). Conclusion: LuTx in children with end-stage PAH resulted in excellent midterm outcomes (100% survival 2 years post-LuTx). Postoperative VA-ECMO facilitates early extubation with rapid gain of allograft function and sustained biventricular reverse-remodeling and systolic function after RV pressure unloading and LV volume loading.

Achieving Interoperable Datasets in Pediatrics: A Data Integration Approach.

Despite their increased secondary value for developing applications and knowledge gain, routine, harmonized and standardized datasets are often not available in Pediatrics. We propose a data integration pipeline towards an interoperable routine dataset in pediatric intensive care medicine. Our three-level approach involves identifying relevant data from primary source systems, developing local data integration processes, and converting data into a standardized, interoperable format using openEHR. We modeled 15 openEHR templates and established 31 interoperable ETL processes, resulting in anonymized, standardized data of about 4,200 pediatric patients that were loaded into a harmonized database. Based on our pipeline and templates, we successfully integrated the first part of this data in our openEHR data repository. We seek to inspire other pediatric intensive care units to adopt similar approaches, with the aim of breaking down heterogenous data silos and promoting secondary use of routine data.

Awareness and diagnosis for intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in neonatal (NICU) and pediatric intensive care units (PICU) - a follow-up multicenter survey.

BACKGROUND: Constantly elevated intra-abdominal pressure (IAH) can lead to abdominal compartment syndrome (ACS), which is associated with organ dysfunction and even multiorgan failure. Our 2010 survey revealed an inconsistent acceptance of definitions and guidelines among pediatric intensivists regarding the diagnosis and treatment of IAH and ACS in Germany. This is the first survey to assess the impact of the updated guidelines on neonatal/pediatric intensive care units (NICU/PICU) in German-speaking countries after WSACS published those in 2013. METHODS: We conducted a follow-up survey and sent 473 questionnaires to all 328 German-speaking pediatric hospitals. We compared our findings regarding awareness, diagnostics and therapy of IAH and ACS with the results of our 2010 survey. RESULTS: The response rate was 48% (n = 156). The majority of respondents was from Germany (86%) and working in PICUs with mostly neonatal patients (53%). The number of participants who stated that IAH and ACS play a role in their clinical practice rose from 44% in 2010 to 56% in 2016. Similar to the 2010 investigations, only a few neonatal/pediatric intensivists knew the correct WSACS definition of an IAH (4% vs 6%). Different from the previous study, the number of participants who correctly defined an ACS increased from 18 to 58% (p < 0,001). The number of respondents measuring intra-abdominal pressure (IAP) increased from 20 to 43% (p < 0,001). Decompressive laparotomies (DLs) were performed more frequently than in 2010 (36% vs. 19%, p < 0,001), and the reported survival rate was higher when a DL was used (85% ± 17% vs. 40 ± 34%). CONCLUSIONS: Our follow-up survey of neonatal/pediatric intensivists showed an improvement in the awareness and knowledge of valid definitions of ACS. Moreover, there has been an increase in the number of physicians measuring IAP in patients. However, a significant number has still never diagnosed IAH/ACS, and more than half of the respondents have never measured IAP. This reinforces the suspicion that IAH and ACS are only slowly coming into the focus of neonatal/pediatric intensivists in German-speaking pediatric hospitals. The goal should be to raise awareness of IAH and ACS through education and training and to establish diagnostic algorithms, especially for pediatric patients. The increased survival rate after conducting a prompt DL consolidates the impression that the probability of survival can be increased by timely surgical decompression in the case of full-blown ACS.

Incidence and prevalence of hamstring injuries in field-based team sports: a systematic review and meta-analysis of 5952 injuries from over 7 million exposure hours.

OBJECTIVE: This study aimed to systematically review and meta-analyse the incidence and prevalence of hamstring injuries in field-based team sports. A secondary aim was to determine the impact of other potential effect moderators (match vs training; sport; playing surface; cohort age, mass and stature; and year when data was collected) on the incidence of hamstring injury in field-based team sports. DESIGN: Systematic review and meta-analysis. DATA SOURCES: CINAHL, Cochrane Library, MEDLINE Complete (EBSCO), Embase, Web of Science and SPORTDiscus databases were searched from database inception to 5 August 2020. ELIGIBILITY CRITERIA: Prospective cohort studies that assessed the incidence of hamstring injuries in field-based team sports. METHOD: Following database search, article retrieval and title and abstract screening, articles were assessed for eligibility against predefined criteria then assessed for methodological quality using the Critical Appraisal Tool for prevalence studies. Meta-analysis was used to pool data across studies, with meta-regression used where possible. RESULTS: Sixty-three articles were included in the meta-analysis, encompassing 5952 injuries and 7 262 168 hours of exposure across six field-based team sports (soccer, rugby union, field hockey, Gaelic football, hurling and Australian football). Hamstring injury incidence was 0.81 per 1000 hours, representing 10% of all injuries. Prevalence for a 9-month period was 13%, increasing 1.13-fold for every additional month of observation (p=0.004). Hamstring injury incidence increased 6.4% for every 1 year of increased average cohort age, was 9.4-fold higher in match compared with training scenarios (p=0.003) and was 1.5-fold higher on grass compared with artificial turf surfaces (p<0.001). Hamstring injury incidence was not significantly moderated by average cohort mass (p=0.542) or stature (p=0.593), was not significantly different between sports (p=0.150) and has not significantly changed over the last 30 years (p=0.269). CONCLUSION: Hamstring injury represents 10% of all injuries in field-based team sports, with 13% of the athletes experiencing a hamstring injury over a 9-month period most commonly during matches. More work is needed to reduce the incidence of hamstring injury in field-based team sports. PROSPERO REGISTRATION NUMBER: CRD42020200022.

Case report: Rescue treatment with add-on selexipag in a preterm infant with suprasystemic pulmonary hypertension, pulmonary capillary hemangiomatosis, and isolated pulmonary vein stenosis.

An extremely dystrophic, premature female infant, born at 25 3/7 weeks of gestational age (birth weight: 430 g) with severe pulmonary hypertension (PH), was admitted to our neonatal intensive care unit (ICU) requiring cardiorespiratory support, including mechanical ventilation and pulmonary vasodilators such as inhaled nitric oxide (iNO) and continuous intravenous sildenafil infusions. The diagnosis of bronchopulmonary dysplasia (BPD) was made. A hemodynamically relevant, persistent ductus arteriosus (PDA) was surgically ligated after failed pharmacologic PDA closure using indomethacin and ibuprofen. The patient was discharged with an estimated 2/3 systemic pulmonary artery pressure. One month after hospital discharge, on low-flow oxygen supplementation (0.5 L/min FiO2 100%), at the corrected age of 16 weeks, she was readmitted to our emergency department with signs of respiratory distress and circulatory decompensation. Echocardiography demonstrated suprasystemic PH. Severe PH persisted despite initiated invasive mechanical ventilation, triple vasodilating therapy [iNO, macitentan, and continuous intravenous (IV) sildenafil], as well as levosimendan, milrinone, and norepinephrine for recompensation from cardiac shock. Thus, we started off-label oral selexipag therapy (oral IP receptor agonist) in the smallest patient reported so far (4 kg body weight). Subsequently, RV systolic pressure decreased to half-systemic, allowing successful weaning of iNO, norepinephrine, and milrinone, and extubation of the patient over 4 days. The infant was discharged 4 weeks after pediatric intensive care unit (PICU) admission in stable cardiorespiratory condition, with an oral, specific, triple antihypertensive PAH-targeted therapy using selexipag, macitentan, and sildenafil as well as oxygen therapy at low-flow (0.5 l/min) and spironolactone. The first cardiac catheterization at the age of 9 months under aforementioned triple PAH-targeted therapy revealed mild PH with 35% systemic PA pressure (mPAP/mSAP = 0.35) and isolated pulmonary vein stenosis. A transthoracic biopsy at the age of 12 months confirmed the diagnosis of BPD and further showed pulmonary interstitial glycogenosis and severe pulmonary capillary hemangiomatosis, without involvement of the pulmonary venules (chILD A2, A3, and B4 according to the Deutsch-Classification). The patient is currently in stable cardiorespiratory condition undergoing triple PH-targeted therapy including selexipag. This report highlights the potential benefits of the oral prostacyclin mimetic selexipag as an early add-on PH-targeted drug in chronic PH of infancy (cPHi).

Acquired von Willebrand syndrome (AVWS) type 2, characterized by decreased high molecular weight multimers, is common in children with severe pulmonary hypertension (PH).

Background and objectives: Emerging evidence suggests that increased degradation of von Willebrand factor and decrease in high molecular weight multimers occurs in patients with pulmonary hypertension (PH). However, the link between acquired von Willebrand Syndrome (AVWS) type 2 and PH remains poorly understood. Material and methods: We retrospectively evaluated the charts of 20 children with PH who underwent bilateral lung transplantation (LuTx) between 2013 and 2022. Von Willebrand variables were determined in 14 of these patients; 11 patients had complete diagnostics including multimer analysis. Results: We confirmed AVWS in 82% of the children studied (9 of 11 patients by multimer analysis). The two remaining patients had suspected AVWS type 2 because of a VWF:Ac/VWF:Ag ratio of <0.7. Platelet dysfunction or suspicion of VWD type 1 were found in two separate patients. All but one of the 14 children with severe PH had a coagulation disorder. Most patients (9 proven, 2 suspected) had AVWS type 2. Notably, 3 of 5 patients (60%) with normal VWF:Ac/VWF:Ag ratio >0.7 had abnormal VWF multimers, indicating AVWS type 2. Hemostatic complications were observed in 4 of 12 (33%) patients with VWS and 3 of 6 (50%) patients without diagnostics and therapy. Conclusion: For children with moderate to severe PH, we recommend systematic analysis of von Willebrand variables, including multimer analysis, PFA-100 and platelet function testing. Awareness of the diagnosis "AVWS" and adequate therapy may help to prevent these patients from bleeding complications in case of surgical interventions or trauma.

Tracing the Progression of Sepsis in Critically Ill Children: Clinical Decision Support for Detection of Hematologic Dysfunction.

BACKGROUND: One of the major challenges in pediatric intensive care is the detection of life-threatening health conditions under acute time constraints and performance pressure. This includes the assessment of pediatric organ dysfunction (OD) that demands extraordinary clinical expertise and the clinician's ability to derive a decision based on multiple information and data sources. Clinical decision support systems (CDSS) offer a solution to support medical staff in stressful routine work. Simultaneously, detection of OD by using computerized decision support approaches has been scarcely investigated, especially not in pediatrics. OBJECTIVES: The aim of the study is to enhance an existing, interoperable, and rule-based CDSS prototype for tracing the progression of sepsis in critically ill children by augmenting it with the capability to detect SIRS/sepsis-associated hematologic OD, and to determine its diagnostic accuracy. METHODS: We reproduced an interoperable CDSS approach previously introduced by our working group: (1) a knowledge model was designed by following the commonKADS methodology, (2) routine care data was semantically standardized and harmonized using openEHR as clinical information standard, (3) rules were formulated and implemented in a business rule management system. Data from a prospective diagnostic study, including 168 patients, was used to estimate the diagnostic accuracy of the rule-based CDSS using the clinicians' diagnoses as reference. RESULTS: We successfully enhanced an existing interoperable CDSS concept with the new task of detecting SIRS/sepsis-associated hematologic OD. We modeled openEHR templates, integrated and standardized routine data, developed a rule-based, interoperable model, and demonstrated its accuracy. The CDSS detected hematologic OD with a sensitivity of 0.821 (95% CI: 0.708-0.904) and a specificity of 0.970 (95% CI: 0.942-0.987). CONCLUSION: We could confirm our approach for designing an interoperable CDSS as reproducible and transferable to other critical diseases. Our findings are of direct practical relevance, as they present one of the first interoperable CDSS modules that detect pediatric SIRS/sepsis-associated hematologic OD.

Towards an Evolutionary Open Pediatric Intensive Care Dataset in the ELISE Project.

BACKGROUND: To embrace the need for freely accessible training data sets originating from the real world, in the ELISE project, we integrate source data from a pediatric intensive care unit and provide it to researchers. OBJECTIVE: We present our vision, initial results and steps on a trail towards an evolutionary open pediatric intensive care data set. METHODS: Our evolution plan for the data set comprises three steps. The final data set will include raw clinical data and labels on critical outcomes such as organ dysfunction and sepsis, generated automatically by computerized and well-evaluated methods. RESULTS: First step resulted in an initial version data set available in a central repository. CONCLUSIONS: Our approach has great potential to provide a comprehensive open intensive care data set labeled for critical pediatric outcomes and, thus, contributing to overcome the current lack of real-world pediatric intensive care data usable for training data-driven algorithms.

DBS emergency surgery for treatment of dystonic storm associated with rhabdomyolysis and acute colitis in DYT-GNAO1.

INTRODUCTION: Patients with variants in the GNAO1 gene may present with life-threatening dystonic storm. There is little experience using pallidal deep brain stimulation (DBS) as an emergency treatment in such cases. CASE DESCRIPTION: We report on a 16-year-old girl with a variant in the GNAO1 gene (c.626G > T; p.(Arg209Leu)) who was admitted to the intensive care unit with medically refractory dystonic storm with secondary complications inducing rhabdomyolysis and acute colitis. Emergency pallidal DBS resulted in rapid improvement of dystonic storm and the subsidence of rhabdomyolysis and colitis. There were no further episodes of dystonic storm during follow-up of 2 years. CONCLUSION: Pallidal DBS is a useful treatment option for GNAO1-related dystonic storm with secondary complications which can be performed as an emergency surgery.

Developing a Data Driven Approach for Early Detection of SIRS in Pediatric Intensive Care Using Automatically Labeled Training Data.

Critical care can benefit from analyzing data by machine learning approaches for supporting clinical routine and guiding clinical decision-making. Developing data-driven approaches for an early detection of systemic inflammatory response syndrome (SIRS) in patients of pediatric intensive care and exploring the possibility of an approach using training data sets labeled automatically beforehand by knowledge-based approaches rather than clinical experts. Using naïve Bayes classifier and an artificial neuronal network (ANN), trained with real data labeled by (1) domain experts ad (2) a knowledge-based decision support system (CDSS). Accuracies were evaluated by the data set labeled by domain experts using a 10-fold cross validation. The ANN approach trained with data labeled by domain experts yielded a specificity of 0.9139 and sensitivity of 0.8979, whereas the approach trained with a data set labeled by a knowledge-based CDSS achieves a specificity of 0.9220 and a sensitivity of 0.8887. ANN yielded promising results for data-driven detection of pediatric SIRS with real data. Our comparison shows the feasibility of using training data labeled automatically by knowledge-based approaches rather than manually allocated by experts.

Full recovery of right ventricular systolic function in children undergoing bilateral lung transplantation for severe PAH.

BACKGROUND: We investigated whether RV function recovers in children with pulmonary arterial hypertension (PAH) and RV failure undergoing lung transplantation (LuTx). METHODS: Prospective observational study of 15 consecutive children, 1.9 to 17.6 years old, with PAH undergoing bilateral LuTx. We performed advanced echocardiography (Echo) and cardiac magnetic resonance imaging (MRI), followed by conventional and strain analysis, pre- and ∼6 weeks post-LuTx. RESULTS: After LuTx, RV/LV end-systolic diameter ratio (Echo), RV volumes and systolic RV function (RVEF 63 vs 30 %; p < 0.05) by MRI completely normalized, even in children with severe RV failure (RVEF < 40%). The echocardiographic end-systolic LV eccentricity index nearly normalized post-LuTx (1.0 vs 2.0, p < 0.0001) while RV hypertrophy regressed more slowly and was still evident. We found especially the end-systolic RV/LV ratios by Echo (diameter: 0.6 vs 2.6) or MRI (volumes: 0.8 vs 3.4) excellent diagnostic tools (p < 0.05): Together with RVEF by MRI, these ratios were superior to tricuspid annular plane systolic excursion (TAPSE; p = 0.4551) in assessing global systolic RV dysfunction. Moreover, children with severe PAH had reduced RV 2D longitudinal strain (Echo, MRI; p = 0.0450) and decreased RV 2D radial and circumferential strain (MRI; p = 0.0026 and p = 0.0036 respectively), all of which greatly improved following LuTx. CONCLUSION: We demonstrate full recovery of RV systolic function in children within two months after LuTx for severe PAH, independently of the patients' age, weight, and hemodynamic compromise preceding the LuTx. Even in end-stage pediatric PAH with poor RV function and low cardiac output, LuTx should be preferred over heart-lung transplantation.

Indications and outcome after lung transplantation in children under 12 years of age: A 16-year single center experience.

OBJECTIVE: Paediatric lung transplantation poses unique management challenges. Experience regarding indications and outcome is scarce, especially in younger children. The primary aim of this study was to investigate outcome after first lung transplantation in children <12 years of age in comparison to adolescents (12-17 years old). METHODS: Records of patients <18 years who underwent first lung transplantation between 01/2005 and 01/2021 were retrospectively reviewed, and compared between children <12 years old and adolescents. Median (IQR) follow-up was 51 (23-91) months. RESULTS: Of the 117 patients underwent first lung transplantation at our institution, of whom 42 (35.8%) patients were <12 years and 75 (64.2%) ≥12 years old. Compared to adolescents, children were more often transplanted for interstitial lung disease (33.3% vs 12%, p = 0.005) and precapillary pulmonary hypertension (28.6% vs 12%, p = 0.025), and required more often intraoperative cardiopulmonary bypass (31% vs 14.7%, p = 0.036) and postoperative ECMO support (47.6% vs 13.3%, p < 0.001). Postoperatively, children required longer ventilation times (78 vs 18 hours, p = 0.009) and longer ICU stay (9.5 vs 3 days, p < 0.001) compared to their older counterparts. Primary graft dysfunction grade 3 at 72 hours (9.5% vs 9.3%, p = 0.999), in-hospital mortality (2.4% vs 6.7%, p = 0.418), graft survival (80% vs 62%, p = 0.479) and freedom from chronic lung allograft dysfunction (76% vs 59%, p = 0.41) at 8-year follow-up did not differ between groups. CONCLUSIONS: Lung transplantation in children under 12 years is challenging due to underlying medical conditions and operative complexity. Nevertheless, outcomes are comparable to those in older children.

Prediction models for SIRS, sepsis and associated organ dysfunctions in paediatric intensive care: study protocol for a diagnostic test accuracy study.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS), sepsis and associated organ dysfunctions are life-threating conditions occurring at paediatric intensive care units (PICUs). Early recognition and treatment within the first hours of onset are critical. However, time pressure, lack of personnel resources, and the need for complex age-dependent diagnoses impede an accurate and timely diagnosis by PICU physicians. Data-driven prediction models integrated in clinical decision support systems (CDSS) could facilitate early recognition of disease onset. OBJECTIVES: To estimate the sensitivity and specificity of previously developed prediction models (index tests) for the detection of SIRS, sepsis and associated organ dysfunctions in critically ill children up to 12 hours before reference standard diagnosis is possible. METHODS AND ANALYSIS: We conduct a monocentre, prospective diagnostic test accuracy study. Clinicians in the PICU of the tertiary care centre Hannover Medical School, Germany, continuously screen and recruit patients until the adaptive sample size (originally intended sample size of 500 patients) is enrolled. Eligible are children (0-17 years, all sexes) who stay in the PICU for ≥12 hours and for whom an informed consent is given. All eligible patients are independently assessed for SIRS, sepsis and organ dysfunctions using corresponding predictive and knowledge-based CDSS models. The knowledge-based CDSS models serve as imperfect reference standards. The assessments are used to estimate the sensitivities and specificities of each predictive model using a clustered nonparametric approach (main analysis). Subgroup analyses ('age groups', 'sex' and 'age groups by sex') are predefined. ETHICS AND DISSEMINATION: This study obtained ethics approval from the Hannover Medical School Ethics Committee (No. 10188_BO_SK_2022). Results will be disseminated as peer-reviewed publications, at scientific conferences, and to patients in an appropriate dissemination approach. TRIAL REGISTRATION NUMBER: This study was registered with the German Clinical Trial Register (DRKS00029071) on 2022-05-23. PROTOCOL VERSION: 10188_BO_SK_2022_V.2.0-20220330_4_Studienprotokoll.

Clinical evaluation of an interoperable clinical decision-support system for the detection of systemic inflammatory response syndrome in critically ill children.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is defined as a non-specific inflammatory process in the absence of infection. SIRS increases susceptibility for organ dysfunction, and frequently affects the clinical outcome of affected patients. We evaluated a knowledge-based, interoperable clinical decision-support system (CDSS) for SIRS detection on a pediatric intensive care unit (PICU). METHODS: The CDSS developed retrieves routine data, previously transformed into an interoperable format, by using model-based queries and guideline- and knowledge-based rules. We evaluated the CDSS in a prospective diagnostic study from 08/2018-03/2019. 168 patients from a pediatric intensive care unit of a tertiary university hospital, aged 0 to 18 years, were assessed for SIRS by the CDSS and by physicians during clinical routine. Sensitivity and specificity (when compared to the reference standard) with 95% Wald confidence intervals (CI) were estimated on the level of patients and patient-days. RESULTS: Sensitivity and specificity was 91.7% (95% CI 85.5-95.4%) and 54.1% (95% CI 45.4-62.5%) on patient level, and 97.5% (95% CI 95.1-98.7%) and 91.5% (95% CI 89.3-93.3%) on the level of patient-days. Physicians' SIRS recognition during clinical routine was considerably less accurate (sensitivity of 62.0% (95% CI 56.8-66.9%)/specificity of 83.3% (95% CI 80.4-85.9%)) when measurd on the level of patient-days. Evaluation revealed valuable insights for the general design of the CDSS as well as specific rule modifications. Despite a lower than expected specificity, diagnostic accuracy was higher than the one in daily routine ratings, thus, demonstrating high potentials of using our CDSS to help to detect SIRS in clinical routine. CONCLUSIONS: We successfully evaluated an interoperable CDSS for SIRS detection in PICU. Our study demonstrated the general feasibility and potentials of the implemented algorithms but also some limitations. In the next step, the CDSS will be optimized to overcome these limitations and will be evaluated in a multi-center study. TRIAL REGISTRATION: NCT03661450 (ClinicalTrials.gov); registered September 7, 2018.

Designing an openEHR-Based Pipeline for Extracting and Standardizing Unstructured Clinical Data Using Natural Language Processing.

BACKGROUND: Merging disparate and heterogeneous datasets from clinical routine in a standardized and semantically enriched format to enable a multiple use of data also means incorporating unstructured data such as medical free texts. Although the extraction of structured data from texts, known as natural language processing (NLP), has been researched at least for the English language extensively, it is not enough to get a structured output in any format. NLP techniques need to be used together with clinical information standards such as openEHR to be able to reuse and exchange still unstructured data sensibly. OBJECTIVES: The aim of the study is to automatically extract crucial information from medical free texts and to transform this unstructured clinical data into a standardized and structured representation by designing and implementing an exemplary pipeline for the processing of pediatric medical histories. METHODS: We constructed a pipeline that allows reusing medical free texts such as pediatric medical histories in a structured and standardized way by (1) selecting and modeling appropriate openEHR archetypes as standard clinical information models, (2) defining a German dictionary with crucial text markers serving as expert knowledge base for a NLP pipeline, and (3) creating mapping rules between the NLP output and the archetypes. The approach was evaluated in a first pilot study by using 50 manually annotated medical histories from the pediatric intensive care unit of the Hannover Medical School. RESULTS: We successfully reused 24 existing international archetypes to represent the most crucial elements of unstructured pediatric medical histories in a standardized form. The self-developed NLP pipeline was constructed by defining 3.055 text marker entries, 132 text events, 66 regular expressions, and a text corpus consisting of 776 entries for automatic correction of spelling mistakes. A total of 123 mapping rules were implemented to transform the extracted snippets to an openEHR-based representation to be able to store them together with other structured data in an existing openEHR-based data repository. In the first evaluation, the NLP pipeline yielded 97% precision and 94% recall. CONCLUSION: The use of NLP and openEHR archetypes was demonstrated as a viable approach for extracting and representing important information from pediatric medical histories in a structured and semantically enriched format. We designed a promising approach with potential to be generalized, and implemented a prototype that is extensible and reusable for other use cases concerning German medical free texts. In a long term, this will harness unstructured clinical data for further research purposes such as the design of clinical decision support systems. Together with structured data already integrated in openEHR-based representations, we aim at developing an interoperable openEHR-based application that is capable of automatically assessing a patient's risk status based on the patient's medical history at time of admission.

Clinical Decision-Support Systems for Detection of Systemic Inflammatory Response Syndrome, Sepsis, and Septic Shock in Critically Ill Patients: A Systematic Review.

BACKGROUND: The design of computerized systems able to support automated detection of threatening conditions in critically ill patients such as systemic inflammatory response syndrome (SIRS) and sepsis has been fostered recently. The increase of research work in this area is due to both the growing digitalization in health care and the increased appreciation of the importance of early sepsis detection and intervention. To be able to understand the variety of systems and their characteristics as well as performances, a systematic literature review is required. Existing reviews on this topic follow a rather restrictive searching methodology or they are outdated. As much progress has been made during the last 5 years, an updated review is needed to be able to keep track of current developments in this area of research. OBJECTIVES: To provide an overview about current approaches for the design of clinical decision-support systems (CDSS) in the context of SIRS, sepsis, and septic shock, and to categorize and compare existing approaches. METHODS: A systematic literature review was performed in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searches for eligible articles were conducted on five electronic bibliographic databases, including PubMed/MEDLINE, IEEE Xplore, Embase, Scopus, and ScienceDirect. Initial results were screened independently by two reviewers based on clearly defined eligibility criteria. A backward as well as an updated search enriched the initial results. Data were extracted from included articles and presented in a standardized way. Articles were classified into predefined categories according to characteristics extracted previously. The classification was performed according to the following categories: clinical setting including patient population and mono- or multicentric study, support type of the system such as prediction or detection, systems characteristics such as knowledge- or data-driven algorithms used, evaluation of methodology, and results including ground truth definition, sensitivity, and specificity. All results were assessed qualitatively by two reviewers. RESULTS: The search resulted in 2,373 articles out of which 55 results were identified as eligible. Over 80% of the articles describe monocentric studies. More than 50% include adult patients, and only four articles explicitly report the inclusion of pediatric patients. Patient recruitment often is very selective, which can be observed from highly varying inclusion and exclusion criteria. The task of disease detection is covered in 62% of the articles; prediction of upcoming conditions in 33%. Sepsis is covered in 67% of the articles, SIRS as sole entity in only 4%, whereas 27% focus on severe sepsis and/or septic shock. The most common combinations of categories "algorithm used" and "support type" are knowledge-based detection of sepsis and data-driven prediction of sepsis. In evaluations, manual chart review (38%) and diagnosis coding (29%) represent the most frequently used ground truth definitions; most studies present a sample size between 10,001 and 100,000 cases (31%) and performances highly differ with only five articles presenting sensitivities and specificities above 90%; four of them using knowledge-based rather than machine learning algorithms. The presentations of holistic CDSS approaches, including technical implementation details, system interfaces, and data and interoperability aspects enabling the use of CDSS in routine settings are missing in nearly all articles. CONCLUSIONS: The review demonstrated the high variety of research in this context successfully. A clear trend is observable toward the use of data-driven algorithms, and a lack of research could be identified in covering the pediatric population as well as acknowledging SIRS as an independent and threatening condition. The quality as well as the significance of the presented evaluations for assessing the performances of the algorithms in clinical routine settings are often not meeting the current standard of scientific work. Our future interest will be concentrated on these realistic settings by implementing and evaluating SIRS detection approaches as well as considering factors to make the CDSS useable in clinical routine from both technical and medical perspectives.

CADDIE2-evaluation of a clinical decision-support system for early detection of systemic inflammatory response syndrome in paediatric intensive care: study protocol for a diagnostic study.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is one of the most critical indicators determining the clinical outcome of paediatric intensive care patients. Clinical decision support systems (CDSS) can be designed to support clinicians in detection and treatment. However, the use of such systems is highly discussed as they are often associated with accuracy problems and 'alert fatigue'. We designed a CDSS for detection of paediatric SIRS and hypothesise that a high diagnostic accuracy together with an adequate alerting will accelerate the use. Our study will (1) determine the diagnostic accuracy of the CDSS compared with gold standard decisions created by two blinded, experienced paediatricians, and (2) compare the system's diagnostic accuracy with that of routine clinical care decisions compared with the same gold standard. METHODS AND ANALYSIS: CADDIE2 is a prospective diagnostic accuracy study taking place at the Department of Pediatric Cardiology and Intensive Care Medicine at the Hannover Medical School; it represents the second step towards our vision of cross-institutional and data-driven decision-support for intensive care environments (CADDIE). The study comprises (1) recruitment of up to 300 patients (start date 1 August 2018), (2) creation of gold standard decisions (start date 1 May 2019), (3) routine SIRS assessments by physicians (starts with recruitment), (4) SIRS assessments by a CDSS (start date 1 May 2019), and (5) statistical analysis with a modified approach for determining sensitivity and specificity and comparing the accuracy results of the different diagnostic approaches (planned start date 1 July 2019). ETHICS AND DISSEMINATION: Ethics approval was obtained at the study centre (Ethics Committee of Hannover Medical School). Results of the main study will be communicated via publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03661450; Pre-results.

A qualitative analysis to identify the elements that support department level change in the life sciences: The PULSE Vision & Change Recognition Program.

The 2011 report, Vision and Change in Undergraduate Biology Education: A Call to Action, provided the impetus to mobilize the undergraduate life sciences education community to affect change in order to enhance the educational experiences of life sciences majors. The work of the appointed Partnership for Undergraduate Life Sciences Education (PULSE) Vision and Change (V&C) Leadership Fellows has focused on the development of programs and resources to support departmental change. In this report, we present a qualitative assessment of several documents generated from the PULSE V&C Leadership Fellow Recognition Team. The Recognition Team developed two initiatives to provide departments with feedback on their change process. The first initiative, the validated PULSE V&C Rubrics, enables departments to collaboratively self-assess their progress in enacting change. The second initiative, the PULSE Recognition Program, involves completion of the aforementioned Rubrics and a site-visit by two Recognition Team members to provide external insights and suggestions to foster a department's change process. Eight departments participated in the Recognition Program in 2014. An evaluation of the documents yielded from the Recognition Program review of seven of the eight departments and a comparison of Rubric scores from before and three years following the site-visits uncovered several common elements required for successful department level change. These elements include an institutional culture that values and supports excellence in teaching and learning with resources and infrastructure, a departmental emphasis on program and course level assessment, and, most importantly, a departmental champion who actively supports endeavors that enhance teaching excellence.