Integrating a new knowledge organisation system for monoclonal antibodies for therapeutic use authorised in Europe into HeTOP terminology-ontology server.

Monoclonal antibodies (MAs) are increasingly used in the therapeutic arsenal. Clinical Data Warehouses (CDWs) offer unprecedented opportunities for research on real-word data. The objective of this work is to develop a knowledge organization system on MAs for therapeutic use (MATUs) applicable in Europe to query CDWs from a multi-terminology server (HeTOP). After expert consensus, three main health thesauri were selected: the MeSH thesaurus, the National Cancer Institute thesaurus (NCIt) and the SNOMED CT. These thesauri contain 1,723 MAs concepts, but only 99 (5.7 %) are identified as MATUs. The knowledge organisation system proposed in this article is a six-level hierarchical system according to their main therapeutic target. It includes 193 different concepts organised in a cross lingual terminology server, which will allow the inclusion of semantic extensions. Ninety nine (51.3 %) MATUs concepts and 94 (48.7 %) hierarchical concepts composed the knowledge organisation system. Two separates groups (an expert group and a validation group) carried out the selection, creation and validation processes. Queries identify, for unstructured data, 83 out of 99 (83.8 %) MATUs corresponding to 45,262 patients, 347,035 hospital stays and 427,544 health documents, and for structured data, 61 out of 99 (61.6 %) MATUs corresponding to 9,218 patients, 59,643 hospital stays and 104,737 hospital prescriptions. The volume of data in the CDW demonstrated the potential for using these data in clinical research, although not all MATUs are present in the CDW (16 missing for unstructured data and 38 for structured data). The knowledge organisation system proposed here improves the understanding of MATUs, the quality of queries and helps clinical researchers retrieve relevant medical information. The use of this model in CDW allows for the rapid identification of a large number of patients and health documents, either directly by a MATU of interest (e.g. Rituximab) but also by searching for parent concepts (e.g. Anti-CD20 Monoclonal Antibody).

Clinical Pharmacist Intervention Reduces Potentially Inappropriate Prescriptions in a Geriatric Perioperative Care Unit Dedicated to Hip Fracture.

INTRODUCTION: Clinical pharmacist (CP) intervention improves drug prescription by identifying potentially inappropriate prescriptions (PIPs). Geriatric perioperative care units (UPOGs) provide enhanced care for patients with hip fracture, including drug prescription. However, it is not known whether adding a CP intervention in a UPOG decreases the number of PIPs. This study aimed to evaluate the effect of a CP intervention, combining an implicit and an explicit method, on the number of PIPs in a UPOG. METHODS: This single centre before-after-control-impact study recruited patients aged over 75 years admitted to a UPOG for a hip fracture. The "control group" ("before period") received usual care including two medication reconciliations, one at admission and one at discharge. The "intervention group" ("after period") received usual care and a CP intervention including two medication reconciliations, a medication review with two tools, STOPP/START and Medication Appropriateness Index, and a meeting between a CP and geriatricians. PIPs were assessed in both groups by STOPP/START and Medication Appropriateness Index and compared from hospital admission to discharge. RESULTS: A total of 209 patients were included, 150 in the control group and 59 in the intervention group (mean age: 87.2 ± 5.9 years). The number of PIPs decreased in both groups from hospital admission to discharge (p < 0.001). The number of PIPs, potentially inappropriate medications, and potential prescribing omissions decreased more in the intervention group than in the control group (adjusted intervention effect: -2.46 (95% CI: -2.63; -2.24); -1.13 (95% CI: -1.27; -0.98); and -1.35 (95% CI: -1.52; -1.18), respectively, p < 0.001 for all). DISCUSSION/CONCLUSION: A CP intervention with an explicit and implicit method improved prescriptions in a UPOG. Further randomized studies are necessary to evaluate the effect of a CP intervention on adverse drug events, health costs, and mortality.

Prehospital Bundle of Care Based on Antibiotic Therapy and Hemodynamic Optimization Is Associated With a 30-Day Mortality Decrease in Patients With Septic Shock.

OBJECTIVES: This study aims to investigate the association between the 30-day mortality in patients with septic shock (SS) and a prehospital bundle of care completion, antibiotic therapy administration, and hemodynamic optimization defined as a fluid expansion of at least 10 mL.kg -1 .hr -1 . DESIGN: To assess the association between prehospital BUndle of Care (BUC) completion and 30-day mortality, the inverse probability treatment weighting (IPTW) propensity method was performed. SETTING: International guidelines recommend early treatment implementation in order to reduce SS mortality. More than one single treatment, a bundle of care, including antibiotic therapy and hemodynamic optimization, is more efficient. PATIENTS: From May 2016 to March 2021, patients with SS requiring prehospital mobile ICU (mICU) intervention were retrospectively analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 529 patients with SS requiring action by the mICU enrolled in this study, 354 (67%) were analyzed. Presumed pulmonary, digestive, and urinary infections were the cause of the SS in 49%, 25%, and 13% of the cases, respectively. The overall 30-day mortality was 32%. Seventy-one patients (20%) received prehospital antibiotic therapy and fluid expansion. Log binomial regression weighted with IPTW resulted in a significant association between 30-day mortality and prehospital BUC completion (respiratory rate [RR] of 0.56 [0.33-0.89]; p = 0.02 and adjusted RR 0.52 [0.27-0.93]; p = 0.03). CONCLUSIONS: A prehospital bundle of care, based on antibiotic therapy and hemodynamic optimization, is associated with a 30-day mortality decrease among patients suffering from SS cared for by an mICU.

Using Clinical Data Warehouse to Optimize the Vaccination Strategy Against COVID-19: A Use Case in France.

Clinical Data Warehouses (CDW) are gold mines and may be useful to manage the COVID-19 outbreak. This article details the use of CDW in order to retrieve patients for vaccination purposes. A list of 34 diseases (or conditions) was published by French Health Authorities to target individuals at a high risk of developing a severe form of COVID. Using a multilevel search engine, 23 queries were built based on structured or unstructured data using natural language processing features. The Diagnosis Related Group coding system was used alone in three queries (13.0%), coupled with unstructured data in four queries (17.4%), and unstructured data were used alone in 16 queries (69.6%). Eleven diseases (conditions) were too broad to be translated into queries. Finally, 6,006 unique re-identified patients were retrieved. This use case demonstrates the usefulness of the Rouen University Hospital CDW in retrieving patients for other purposes than translational research.

OntoBioStat: Supporting Causal Diagram Design and Analysis.

Suitable causal inference in biostatistics can be best achieved by knowledge representation thanks to causal diagrams or directed acyclic graphs. However, necessary and sufficient causes are not easily represented. Since existing ontologies do not fill this gap, we designed OntoBioStat in order to enable covariate selection support based on causal relation representations. OntoBioStat automatic ontological causal diagram construction and inferences are detailed in this study. OntoBioStat inferences are allowed by Semantic Web Rule Language rules and axioms. First, statements made by the users include outcome, exposure, covariate, and causal relation specification. Then, reasoning enable automatic construction using generic instances of Meta_Variable and Necessary_Variable classes. Finally, inferred classes highlighted potential bias such as confounder-like. Ontological causal diagram built with OntoBioStat was compared to a standard causal diagram (without OntoBioStat) in a theoretical study. It was found that confounding and bias were not completely identified by the standard causal diagram, and erroneous covariate sets were provided. Further research is needed in order to make OntoBioStat more usable.

Evaluation of Doc'EDS: a French semantic search tool to query health documents from a clinical data warehouse.

BACKGROUND: Unstructured data from electronic health records represent a wealth of information. Doc'EDS is a pre-screening tool based on textual and semantic analysis. The Doc'EDS system provides a graphic user interface to search documents in French. The aim of this study was to present the Doc'EDS tool and to provide a formal evaluation of its semantic features. METHODS: Doc'EDS is a search tool built on top of the clinical data warehouse developed at Rouen University Hospital. This tool is a multilevel search engine combining structured and unstructured data. It also provides basic analytical features and semantic utilities. A formal evaluation was conducted to measure the impact of Natural Language Processing algorithms. RESULTS: Approximately 18.1 million narrative documents are stored in Doc'EDS. The formal evaluation was conducted in 5000 clinical concepts that were manually collected. The F-measures of negative concepts and hypothetical concepts were respectively 0.89 and 0.57. CONCLUSION: In this formal evaluation, we have shown that Doc'EDS is able to deal with language subtleties to enhance an advanced full text search in French health documents. The Doc'EDS tool is currently used on a daily basis to help researchers to identify patient cohorts thanks to unstructured data.

Evaluation of a deep learning model on coronary CT angiography for automatic stenosis detection.

PURPOSE: The purpose of this study was to evaluate a deep-learning model (DLM) for classifying coronary arteries on coronary computed tomography -angiography (CCTA) using the Coronary Artery Disease-Reporting and Data System (CAD-RADS). MATERIALS AND METHODS: The DLM was trained with 10,800 curved multiplanar reformatted (cMPR) CCTA images classified by an expert radiologist using the CAD-RADS. For each of the three main coronary arteries, nine cMPR images 40° apart acquired around each arterial circumference were then classified by the DLM using the highest probability. For the validation set composed of 159 arteries from 53 consecutive patients, the images were read by two senior and two junior readers; consensus of the two seniors was the reference standard. With the DLM, the majority vote for the nine images was used to classify each artery. Three groups (CAD-RADS 0, 1-2, or 3-4-5) and 2 groups CAD-RADS 0-1-2 or 3-4-5 (<50% vs. ≥50% stenosis) were used for comparisons with readers and consensus. Performance of the model and readers was compared to the consensus reading using the intraclass coefficient (ICC) and Cohen's kappa coefficient at the artery and patient levels. RESULTS: With the three groups at the artery level, the ICC of the DLM was 0.82 (95% CI: 0.75-0.88) and not significantly different from those of 3/4 readers; accuracy was 81%. With the binary classification, Cohen kappa coefficient of the DLM was 0.85 (95% CI: 0.69-0.94) and not significantly different from that of 3/4 readers; accuracy was 96%. At the patient level, sensitivity and specificity were 93% and 97% respectively, and the negative predictive value was 97%. CONCLUSION: The DLM detected ≥50% stenoses with performances similar to those achieved by senior radiologists.

Telemedicine in French Memory Clinics During the COVID-19 Pandemic.

This multicenter study was conducted in French memory clinics during the first COVID-2019 lockdown (March-May 2020). The objective was to evaluate the effect of a telemedicine consultation on treatment modification in dementia care. Among 874 patients who had a telemedicine consultation, 103 (10.7%) had treatment modifications, in particular those living with a relative or diagnosed with Alzheimer's disease. A control group of patients referred March-May 2019 was also included. Treatment modification rate was similar between periods with an adjusted percentage difference of -4% (p = 0.27). Telemedicine consultations allowed treatment modifications with only a minor short-term negative impact on therapeutic strategies.

Dynamic metabolic changes measured by indirect calorimetry during the early phase of septic shock: a prospective observational pilot study.

BACKGROUND AND AIMS: Energy metabolism (energy deficit, substrate consumption) in the early phase of septic shock is not clearly understood. The objective of this study was to describe its evolution using indirect calorimetry. METHODS: Prospective observational pilot study including ventilated adult patients with septic shock admitted in a surgical intensive care unit (ICU). Metabolic data were collected using the COSMED Q-NRG + ® calorimeter: carbon dioxide production (VCO2), oxygen consumption (VO2), resting energy expenditure (REE), respiratory quotient (RQ) and the rate of substrate utilization (proteins, lipids, and carbohydrates). The main criterion was the evolution of the energy deficit (dE) from D1 to D6. RESULTS: In total, 34 patients were included and 15 patients (age: 57.6 ± 12.8 years; Simplified Acute Physiology Score II: 52 ± 11) were eligible for final analysis. Time for initiation of nutritional support was 2.5 ± 1.5 days. The dE improved during the study period (slope = 2.9 [1.8; 4.2]; p < 0.001). The REE remained stable during the first week with no significant variation (slope = -0.16 [-1.49; 0.79]; p = 0.78). The RQ remained stable overall (slope = 0.01 [0.00; 0.03]; p = 0.10). The substrates utilization significantly changed at D3 in favor of protein consumption (slope = 6.50 [4.44; 8.85]; p < 0.001) with an overall significant decrease in the consumption of non-protein substrates. CONCLUSION: Energy deficit improved while REE and RQ remained relatively stable during the first week of ICU stay. The significance of the variations of substrates consumption was unclear. These preliminary results should be further explored with larger studies.

Role of MDCT in evaluating prothesis size prior to percutaneous transcatheter closure of ostium secundum atrial septal defect.

To investigate the feasibility and accuracy of cardiac multidetector computed tomography (MDCT) prosthesis sizing prior to ostium secundum atrial septal defect (ASD) percutaneous closure. Seventy consecutive patients were included in this retrospective bicentric study between May 2012 and June 2018. All underwent cardiac MDCT (primarily performed to rule out abnormal venous pulmonary return and coronary anomaly) and transesophageal echocardiography (TEE) before transcatheter closure: dimensions of the defect and peripheral rims were measured. Measurements of the defect obtained at TEE and MDCT were compared to prosthesis size. Our primary objective was the comparison of ASD maximal diameter obtained at MDCT (CT-Dmax) to prosthesis size. Intraclass correlation coefficient (ICC), Bland Altman plots and linear regression were calculated. Intra- and inter-observer agreements were calculated for MDCT defect measurements. Forty-three patients were finally included for defect measurements: 17 patients did not undergo transcatheter closure, and 10 had incomplete data. For CT-Dmax, ICC was 0.88 (CI 95% = [0.78-0.93]; p = 0.06); mean difference was - 0.8 ± 5.7 mm; regression linear equation was 0.9 × + 3.2 (p < 0.001). For maximal diameter at TEE versus prosthesis size, ICC was 0.46 (CI 95% = [0.21-0.61]; p = 0.003); mean difference was-6.0 ± 8.2 mm; regression linear equation was 0.91 × + 7.6 (p < 0.001). Intra- and inter-observer agreement for CT-Dmax were 0.97 (CI 95% = [0.95-0.98]) and 0.86 (CI 95% = [0.73-0.93]) respectively. MDCT is a reliable tool for sizing the defect of ostium secundum ASD, making it a complement or even an alternative to pre-procedural TEE.

Valvular and infection-associated risk factors as criteria to guide the use of echocardiography in patients with native joint infections.

BACKGROUND: Native joint and bone infections (NJBI) are associated with infective endocarditis (IE) in 15% of cases. There are no studies analyzing the use of cardiac imaging in cases of NJBI. The objective of this study was to identify factors associated with echocardiography suggestive of IE in patients with NJBI. METHODS: This medical records review was conducted in patients hospitalized for NJBI between 2007 and 2017 in Rheumatology and Infectious Diseases departments of 2 university hospitals. Patients included had a microbiologically proven NJBI during their hospitalization. RESULTS: In this cohort of 546 patients, median age 66 years, echocardiography was suggestive of IE in 66 (12%). In multivariate analysis, factors associated with echocardiography suggestive of IE were 2 or more positive blood cultures (OR 11.55 (CI95% 3.24-74.20)), cardiac conditions with a high risk of IE (OR 7.34 (CI95% 2.95-18.61)), unknown heart murmur (OR 4.59 (CI95% 1.79-11.74)), multifocal infection (OR 2.26 (CI95% 1.21-4.23)) and an infection due to S. bovis (OR 3.52 (CI95% 1.26-9.79)). The factor associated with the absence of an echocardiography evocative of IE was infection due to unconventional bacteria for IE (OR 0.13 (CI95% 0.01-0.76)). According to the factors associated with echocardiography evocative of IE, we propose the Normandy score based on three kinds of data: cardiac condition, bacterial strain and NJBI mechanism. Echocardiography should be realized when this score, whose negative predictive value is 100% CI95% (98-100%) for prescription of echocardiography, is more than zero. CONCLUSIONS: A score based on valvular condition, bacterial strain and NJBI mechanism could guide clinicians in prescribing echocardiography during NJBI with an excellent negative predictive value.

Ontological Models Supporting Covariates Selection in Observational Studies.

In the context of causal inference, biostatisticians use causal diagrams to select covariates in order to build multivariate models. These diagrams represent datasets variables and their relations but have some limitations (representing interactions, bidirectional causal relations). The MetBrAYN project aims at building an ontological-based process to tackle these issues. The knowledge acquired by the biostatistician during a methodological consultation for a research question will be represented in a general ontology. In order to aggregate various forms of knowledge the ontology will act as a wrapper. Ontology-based causal diagrams will be semi-automatically built. Founded on inference rules, the global system will help biostatisticians to curate it and to visualize recommended covariates for their research question.

Gene Expression of Protein Tyrosine Phosphatase 1B and Endoplasmic Reticulum Stress During Septic Shock.

Introduction: Protein Tyrosine Phosphatase 1B (PTP1B) and endoplasmic reticulum stress (ERS) are involved in the septic inflammatory response. Their inhibition is associated with improved survival in murine models of sepsis. The objective was to describe PTP1B and ERS expression during septic shock in human. Material and Methods: Prospective study including patients admitted to intensive care unit (ICU) for septic shock. Blood samples were collected on days 1 (D1), 3 and 5 (D5). Quantitative PCR (performed from whole blood) evaluated the expression of genes coding for PTP1B (PTPN1) and key elements of ERS (GRP78, ATF6, CHOP) or for endothelial dysfunction-related markers (ICAM1 and ET1). We analyzed gene variation between D5 and D1, collected glycemic parameters, insulin resistance and organ failure was evaluated by Sequential Organ Failure Assessment (SOFA) score. Results: We included 44 patients with a mean SAPS II 50 ± 16 and a mortality rate of 13.6%. Between D1 and D5, there was a significant decrease of PTPN1 (p < 0.001) and ATF6 (p < 0.001) expressions. Their variations of expression were correlated with SOFA variation (PTPN1, r = 0.35, CI 95% [0.05; 0.54], p = 0.03 and ATF6, r = 0.45 CI 95% [0.20; 0.65], p < 0.001). We did not find any correlation between PTPN1 expression and insulin resistance or glycemic parameters. Between D1 and D5, ATF6 and PTPN1 expressions were correlated with that of ET1. Conclusions: Our study has evaluated for the first time the expression of PTP1B and ERS in patients with septic shock, revealing that gene expression variation of PTPN1 and ATF6 are partly correlated with the evolution of septic organ failure and with endothelial dysfunction markers expression.

The Modified Sliding Alar Cartilage Flap: A Novel Way to Preserve the Internal Nasal Valve as Illustrated by Three-Dimensional Modeling.

BACKGROUND: Preservation of the scroll area is essential when performing rhinoplasty to achieve a good functional outcome. This is of particular concern with tip-plasty procedures. The objectives of this study were (1) to describe a novel tip-plasty procedure consisting of sliding the cephalic portion of the alar cartilage beneath its caudal portion to preserve the scroll area and (2) to present the authors' prospective case series, which includes Nasal Obstruction Symptom Evaluation and peak nasal inspiratory flow scores to objectively evaluate functional outcomes. METHODS: The modified sliding alar cartilage surgical technique is described and illustrated by intraoperative photographs and videos and by three-dimensional modeling software. A prospective study of all patients undergoing tip-plasty with alar reduction by the sliding alar cartilage technique was performed from September of 2016 to December of 2017. Peak nasal inspiratory flow and Nasal Obstruction Symptom Evaluation scores were collected preoperatively and at 1 week and 6 months postoperatively. RESULTS: Twenty-five patients were included in the study. Aesthetic outcomes were good, with no major complications. The average preoperative peak nasal inspiratory flow score was 114 liters/minute (95 percent CI, 108.1321 to 119.8679 liters/minute), whereas the average score at 6 months postoperatively was 115.82 liters/minute (95 percent CI, 106.6241 to 125.0159 liters/minute; p = 0.513). The average preoperative Nasal Obstruction Symptom Evaluation score was 17.2 (95 percent CI, 15.99655 to 18.40345), whereas the average score at 6 months postoperatively was 15.2 (95 percent CI, 13.18131 to 17.21869; p = 0.08353), indicating no significant change. CONCLUSION: The sliding alar cartilage is a simple technique allowing tip definition while maintaining nasal airway function by preserving the crucial anatomical scroll area. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

White matter tracts lesions and decline of verbal fluency after deep brain stimulation in Parkinson's disease.

Decline of verbal fluency (VF) performance is one of the most systematically reported neuropsychological adverse effects after subthalamic nucleus deep brain stimulation (STN-DBS). It has been suggested that this worsening of VF may be related to a microlesion due to the electrode trajectories. We describe the disruption of surrounding white matter tracts following electrode implantation in Parkinson's disease (PD) patients with STN-DBS and assess whether damage of fiber pathways is associated with VF impairment after surgery. We retrospectively analyzed 48 PD patients undergoing bilateral STN DBS. The lesion mask along the electrode trajectory transformed into the MNI 152 coordinate system, was compared with white matter tract atlas in Tractotron software, which provides a probability and proportion of fibers disconnection. Combining tract- and atlas-based analysis reveals that the trajectory of the electrodes intersected successively with the frontal aslant tract, anterior segment of arcuate tract, the long segment of arcuate tract, the inferior longitudinal fasciculus, the superior longitudinal fasciculus, the anterior thalamic radiation, and the fronto striatal tract. We found no association between the proportion fiber disconnection and the severity of VF impairment 6 months after surgery. Our findings demonstrated that microstructural injury associated with electrode trajectories involved white matter bundles implicated in VF networks.