Enhancing Healthcare Informatics: Integrating Category Theory Reasoning into OMOP-CDM Ontology Model.

The task of managing diverse electronic health records requires the consolidation of data from different sources to facilitate clinical research and decision-making support, with the emergence of the Observational Medical Outcomes Partnership - Common Data Model (OMOP-CDM) as a standard relational database schema for structuring health records from different sources. Working with ontologies is strongly associated with reasoners. Implementing them over expansive and intricate Ontologies can pose computational challenges, potentially resulting in slow performance. In this paper, we propose the implementation of a new reasoner based on categorical logic over a translation of OMOP-CDM into an ontology model. This enables enhancements to the efficiency and scalability of implementing such models.

Transforming Primary Care Data Into the Observational Medical Outcomes Partnership Common Data Model: Development and Usability Study.

Background: Patient-monitoring software generates a large amount of data that can be reused for clinical audits and scientific research. The Observational Health Data Sciences and Informatics (OHDSI) consortium developed the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to standardize electronic health record data and promote large-scale observational and longitudinal research. Objective: This study aimed to transform primary care data into the OMOP CDM format. Methods: We extracted primary care data from electronic health records at a multidisciplinary health center in Wattrelos, France. We performed structural mapping between the design of our local primary care database and the OMOP CDM tables and fields. Local French vocabularies concepts were mapped to OHDSI standard vocabularies. To validate the implementation of primary care data into the OMOP CDM format, we applied a set of queries. A practical application was achieved through the development of a dashboard. Results: Data from 18,395 patients were implemented into the OMOP CDM, corresponding to 592,226 consultations over a period of 20 years. A total of 18 OMOP CDM tables were implemented. A total of 17 local vocabularies were identified as being related to primary care and corresponded to patient characteristics (sex, location, year of birth, and race), units of measurement, biometric measures, laboratory test results, medical histories, and drug prescriptions. During semantic mapping, 10,221 primary care concepts were mapped to standard OHDSI concepts. Five queries were used to validate the OMOP CDM by comparing the results obtained after the completion of the transformations with the results obtained in the source software. Lastly, a prototype dashboard was developed to visualize the activity of the health center, the laboratory test results, and the drug prescription data. Conclusions: Primary care data from a French health care facility have been implemented into the OMOP CDM format. Data concerning demographics, units, measurements, and primary care consultation steps were already available in OHDSI vocabularies. Laboratory test results and drug prescription data were mapped to available vocabularies and structured in the final model. A dashboard application provided health care professionals with feedback on their practice.

Efficacy of high-flow nasal oxygen therapy started in the emergency room versus conventional oxygen therapy in patients with acute hypoxaemic respiratory distress: protocol for a French multicentric, prospective, open and randomised superiority study protocol (HIFLOWED).

INTRODUCTION: Acute respiratory failure is a life-threatening condition frequently found in the emergency department. High-flow nasal oxygen (HFNO) is increasingly used in emergency departments for patients with hypoxaemic acute respiratory failure. However, despite the increasing number of studies, its potential advantages regarding the need for therapeutic escalation and mortality have not been precisely evaluated. Our objective is to compare conventional oxygen therapy to HFNO when they are initiated during the first hour following the patient's arrival at the emergency department, with the hypothesis that HFNO would reduce the need for ventilatory therapy escalation. METHODS AND ANALYSIS: This is a multicentric, prospective, open and randomised superiority study. 500 inpatients will be randomised (1:1) to receive conventional oxygen therapy or HNFO. The primary outcome is a failure in the oxygen therapy defined as the need for a therapeutic escalation within 4 hours after therapy initiation. ETHICS AND DISSEMINATION: The study has been submitted and approved by the Comité de Protection des Personnes Nord Ouest IV (20 October 2020). As required, a notification was sent to the Agence nationale de sécurité du médicament et des produits de santé (22 October 2020). The research results will be published in peer-reviewed publications and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT04607967.

When and which second-line workup to perform for uveitis: a tertiary care center experience.

OBJECTIVE: Uveitis are inflammatory disorders of various etiologies. The first-line etiological workup is currently poorly codified, and some patients undergo sequential investigations. However, what leads the clinician to perform subsequent exams and the relevance of such exams remain to be determined. The main objective of the study was to evaluate the relevance and modalities of a second-line workup of patients with uveitis. MATERIALS AND METHODS: We performed a monocentric retrospective study in Nancy University Hospital. All adult patients who underwent an etiological workup in the Internal Medicine Department between January 2014 and December 2021 were included. RESULTS: Among the 247 patients included, 52 underwent a second-line workup, resulting in a modified diagnosis for 18 of them (34.6%), mainly sarcoidosis, intraocular lymphoma, and Crohn's disease. On multivariate analysis, a follow-up longer than 40 months and idiopathic uveitis were associated with the realization of a second-line workup (OR = 2.97 [1.58 - 5.61]; p = 0.001, and OR = 6.13 [2.3-16.1]; p < 0.01, respectively). The presence of synechia and ocular granuloma were associated with a modification of the diagnosis (OR = 8.03 [1.85-45.48]; p = 0.01, and OR = 5.14 [1.22-24.78]; p = 0.03, respectively). CONCLUSION: The second-line workup is relevant in up to one-third of patients, mainly if presenting with a modification of ophthalmological examination, synechiae, and a granulomatous feature, and should focus on intraocular lymphoma, sarcoidosis, and Crohn's disease. Larger studies are needed to provide guidelines for second-line workup.

Current status of the small molecule anti-HIV drugs in the pipeline or recently approved.

Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS) with high morbidity and mortality rates. Treatment of AIDS/HIV is being complicated by increasing resistance to currently used antiretroviral (ARV) drugs, mainly in low- and middle-income countries (LMICs) due to drug misuse, poor drug supply and poor treatment monitoring. However, progress has been made in the development of new ARV drugs, targeting different HIV components (Fig. 1). This review aims at presenting and discussing the progress made towards the discovery of new ARVs that are at different stages of clinical trials as of July 2024. For each compound, the mechanism of action, target biomolecule, genes associated with resistance, efficacy and safety, class, and phase of clinical trial are discussed. These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new classes which can delay the development of resistance.

FIGNL1-FIRRM is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading.

During meiosis, nucleoprotein filaments of the strand exchange proteins RAD51 and DMC1 are crucial for repairing SPO11-generated DNA double-strand breaks (DSBs) by homologous recombination (HR). A balanced activity of positive and negative RAD51/DMC1 regulators ensures proper recombination. Fidgetin-like 1 (FIGNL1) was previously shown to negatively regulate RAD51 in human cells. However, FIGNL1's role during meiotic recombination in mammals remains unknown. Here, we decipher the meiotic functions of FIGNL1 and FIGNL1 Interacting Regulator of Recombination and Mitosis (FIRRM) using male germline-specific conditional knock-out (cKO) mouse models. Both FIGNL1 and FIRRM are required for completing meiotic prophase in mouse spermatocytes. Despite efficient recruitment of DMC1 on ssDNA at meiotic DSB hotspots, the formation of late recombination intermediates is defective in Firrm cKO and Fignl1 cKO spermatocytes. Moreover, the FIGNL1-FIRRM complex limits RAD51 and DMC1 accumulation on intact chromatin, independently from the formation of SPO11-catalyzed DSBs. Purified human FIGNL1ΔN alters the RAD51/DMC1 nucleoprotein filament structure and inhibits strand invasion in vitro. Thus, this complex might regulate RAD51 and DMC1 association at sites of meiotic DSBs to promote proficient strand invasion and processing of recombination intermediates.

Retinal redetachment after silicone oil removal: a risk factor analysis.

PURPOSE: To report the rate of retinal redetachment after silicone oil removal following rhegmatogenous retinal detachment surgery and to determine potential risk factors. METHODS: Retrospective observational case series of 161 eyes who underwent rhegmatogenous retinal detachment surgery and subsequent silicone oil removal. Pre- and intraoperative risk factors were evaluated using univariate and multivariate logistic regression. We also evaluated the effect of tamponade duration on anatomical outcomes. RESULTS: The median tamponade duration was 5.9 [4.3;7.6] months. Seventeen (10.6%) eyes underwent silicone oil removal within 3 months of surgery, with a median delay of 2.3 [2.0;2.8] months. The rate of retinal detachment after silicone oil removal was 14.9%. A history of previous unsuccessful surgery was the only significant risk factor for retinal redetachment after silicone oil removal (OR 4.8, 95%CI [1.5;19.0], p = 0.02). The use of 360° laser retinopexy and concomitant air or gas tamponade during silicone oil removal were not found to affect the redetachment rate. Eyes with silicone oil tamponade ≤ 3 months showed an increased, albeit not significant, risk of developing recurrent rhegmatogenous retinal detachment after silicone oil removal (35.3% versus 12.5%, p = 0.06). CONCLUSION: A retinal redetachment occurred in 14.9% of eyes undergoing silicone oil removal following rhegmatogenous retinal detachment surgery. Previous failed surgery was associated with a 4.8-fold increased risk of developing recurrent rhegmatogenous retinal detachment after silicone oil removal. Eyes with silicone oil tamponade ≤ 3 months tended to have a higher redetachment rate. TRIAL REGISTRATION NUMBER: ID NCT05647928 (12th April 2022).

Interactions Between Eosinophils and IL5Rα+ Mast Cells in Non-Advanced Systemic Mastocytosis.

BACKGROUND: Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown. OBJECTIVE: To describe blood and BM eosinophil characteristics in SM. METHODS: A large collection of BM biopsies was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining, and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence. RESULTS: Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in non-advanced-SM (n=37 BM biopsies) compared to both controls (n=8, p=0.0003) and to advanced SM (n=24, p=0.014). In non-advanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r=0.38, p=0.038), eosinophils count in BM biopsies (r=0.45, p=0.007), EPX staining (r=0.37, p=0.035) and eosinophil degranulation (r=0.39, p=0.023). Eosinophil counts in BM biopsies also correlated with MC counts (r=0.47, p=0.006) and KIT staining surface (r=0.49, p=0.003). BM MCs expressed interleukin-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils display several increased surface markers compared to controls, suggesting an activated state. CONCLUSION: Our data suggest a possible crosstalk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in non-advanced-SM not fully controlled by other therapies.

Performance of the ERC/ESICM-recommendations for neuroprognostication after cardiac arrest: insights from a prospective multicenter cohort.

Brief abstract: In a multicentre network of 28 ICUs in France and Belgium, all comatose patients who fulfilled the 2021 ERC-ESICM criteria for poor outcome after cardiac arrest died or survived with severe neurological disability, even after excluding patients with active WLST to limit self-fulfilling prophecy bias. However, in almost half of the patients, these criteria were not fulfilled, resulting in an indeterminate outcome; in these patients, normal NSE levels and benign EEG predicted neurological recovery, helping reduce prognostic uncertainty. AIM: To investigate the performance of the 2021 ERC/ESICM-recommended algorithm for predicting poor outcome after cardiac arrest (CA) and potential tools for predicting neurological recovery in patients with indeterminate outcome. METHODS: Prospective, multicenter study on out-of-hospital CA survivors from 28 ICUs of the AfterROSC network. In patients comatose with a Glasgow Coma Scale motor score ≤3 at ≥72 hours after resuscitation, we measured: 1) the accuracy of neurological examination, biomarkers (neuron-specific enolase, NSE), electrophysiology (EEG and SSEP) and neuroimaging (brain CT and MRI) for predicting poor outcome (modified Rankin scale score≥4 at 90 days), and 2) the ability of low or decreasing NSE levels and benign EEG to predict good outcome in patients whose prognosis remained indeterminate. RESULTS: Among 337 included patients, the ERC-ESICM algorithm predicted poor neurological outcome in 175 patients, of whom 106 (60%) had withdrawal of life-sustaining treatment (WLST). Among the 69 patients without active WLST, the positive predictive value for an unfavourable outcome was 100% [95-100]%. The specificity of individual predictors ranged from 90% for EEG to 100% for clinical examination and SSEP. Among the remaining 162 patients with indeterminate outcome, a combination of 2 favourable signs predicted good outcome with 99[96-100]% specificity and 23[11-38%]% sensitivity. Conclusion All comatose resuscitated patients not undergoing WLST who fulfilled the ERC-ESICM criteria for poor outcome after CA had poor outcome at three months, even if a self-fulfilling prophecy cannot be completely excluded. In patients with indeterminate outcome (half of the population), favourable signs predicted neurological recovery, reducing prognostic uncertainty.

Tracheal intubation in critically ill adults with a physiologically difficult airway. An international Delphi study.

PURPOSE: Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA). METHODS: An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician-researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements. RESULTS: The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care. CONCLUSION: Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

Population Pharmacokinetic of vancomycin administered by continuous infusion in critically ill patients.

INTRODUCTION: Administration of vancomycin dose by continuous infusion (CI) according to population pharmacokinetic (Pop Pk) models is highly recommended in critically ill patients who exhibit pathophysiological changes. OBJECTIVE: to develop and validate a Pop Pk model of vancomycin administered by CI in critically ill patients with normal and impaired renal functions. METHODS: The Pop Pk study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (gender, age, weight, height, and creatinine clearance Cr-Cl) was tested on the model's Pk parameters. The performance of the final model was assessed using an external dataset. RESULTS: A one-compartment model (Volume of distribution; Vd, Elimination from compartement; Ke) was found to show a good prediction performance. The influence of covariates has shown that age and Cr-Cl affected significantly Vd and Ke respectively. The distribution of simulated vancomycin clearance (CLv) according to different renal function levels showed anegative correlation between CLv and the severity of the renal impairment. The Internal validation of the final model showed that the plot of individual predicted concentration versus observed concentration resulted in r² = 0.86 in the final model.The external validation of the final model showed an acceptable predictive performance. CONCLUSION: We developed a Pop Pk model for vancomycin administered by CI in critically ill patients. A significant impact of Cr-Cl and different stages of renal failure on CLv has been demonstrated. The establishment of an individualized proposal dose based on this model may be helpful to achieve the therapeutic target range which is critical in optimizing the efficacy and safety of this antibiotic.

Access to primary care and mortality in excess for patients with cancer in France: Results from 21 French Cancer Registries.

BACKGROUND: The impact of geographical accessibility on cancer survival has been investigated in few studies, with most research focusing on access to reference care centers, using overall mortality and limited to specific cancer sites. This study aims to examine the association of access to primary care with mortality in excess of patients with the 10 most frequent cancers in France, while controlling for socioeconomic deprivation. METHODS: This study included a total of 151,984 cases diagnosed with the 10 most common cancer sites in 21 French cancer registries between 2013 and 2015. Access to primary care was estimated using two indexes: the Accessibilité Potentielle Localisée index (access to general practitioners) and the Scale index (access to a range of primary care clinicians). Mortality in excess was modelized using an additive framework based on expected mortality based on lifetables and observed mortality. FINDINGS: Patients living in areas with less access to primary care had a greater mortality in excess for some very common cancer sites like breast (women), lung (men), liver (men and women), and colorectal cancer (men), representing 46% of patients diagnosed in our sample. The maximum effect was found for breast cancer; the excess hazard ratio was estimated to be 1.69 (95% CI, 1.20-2.38) 1 year after diagnosis and 2.26 (95% CI, 1.07-4.80) 5 years after diagnosis. INTERPRETATION: This study revealed that this differential access to primary care was associated with mortality in excess for patients with cancer and should become a priority for health policymakers to reduce these inequalities in health care accessibility.

Comparative life cycle assessment of excreta management systems through composting and biomethanization: Case of a low-income tropical country.

Low-income tropical regions, such as Haiti, grapple with environmental issues stemming from inadequate sanitation infrastructure for fecal sludge management. This study scrutinizes on-site sanitation systems in these regions, evaluating their environmental impacts and pinpointing improvement opportunities. The focus is specifically on systems integrating excreta valorization through composting and/or anaerobic digestion. Each system encompasses toilet access, evacuation, and sludge treatment. A comparative life cycle assessment was undertaken, with the functional unit managing one ton of excreta in Haiti over a year. Six scenarios representing autonomous sanitation systems were devised by combining three toilet types (container-based toilets (CBTs), ventilated improved pit (VIP) latrines, and flush toilets (WC)) with two sludge treatment processes (composting and biomethanization). Biodigester-based systems exhibited 1.05 times higher sanitary impacts and 1.03 times higher ecosystem impacts than those with composters. Among toilet types, CBTs had the lowest impacts, followed by VIP latrines, with WCs having the highest impacts. On average, WC scenarios were 3.85 times more impactful than VIP latrines and 4.04 times more impactful than those with CBTs regarding human health impact. Critical variables identified include the use of toilet paper, wood shavings, greenhouse gas emissions, and construction materials.

A systematic review of the value of clinical decision support systems in the prescription of antidiabetic drugs.

INTRODUCTION: The management of chronic diabetes mellitus and its complications demands customized glycaemia control strategies. Polypharmacy is prevalent among people with diabetes and comorbidities, which increases the risk of adverse drug reactions. Clinical decision support systems (CDSSs) may constitute an innovative solution to these problems. The aim of our study was to conduct a systematic review assessing the value of CDSSs for the management of antidiabetic drugs (AD). MATERIALS AND METHODS: We systematically searched the scientific literature published between January 2010 and October 2023. The retrieved studies were categorized as non-specific or AD-specific. The studies' quality was assessed using the Mixed Methods Appraisal Tool. The review's results were reported in accordance with the PRISMA guidelines. RESULTS: Twenty studies met our inclusion criteria. The majority of AD-specific studies were conducted more recently (2020-2023) compared to non-specific studies (2010-2015). This trend hints at growing interest in more specialized CDSSs tailored for prescriptions of ADs. The nine AD-specific studies focused on metformin and insulin and demonstrated positive impacts of the CDSSs on different outcomes, including the reduction in the proportion of inappropriate prescriptions of ADs and in hypoglycaemia events. The 11 nonspecific studies showed similar trends for metformin and insulin prescriptions, although the CDSSs' impacts were not significant. There was a predominance of metformin and insulin in the studied CDSSs and a lack of studies on ADs such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. CONCLUSION: The limited number of studies, especially randomized clinical trials, interested in evaluating the application of CDSS in the management of ADs underscores the need for further investigations. Our findings suggest the potential benefit of applying CDSSs to the prescription of ADs particularly in primary care settings and when targeting clinical pharmacists. Finally, establishing core outcome sets is crucial for ensuring consistent and standardized evaluation of these CDSSs.

Bulbar muscle impairment in patients with late onset Pompe disease: Insight from the French Pompe registry.

BACKGROUND AND PURPOSE: Late onset Pompe disease (LOPD) is a rare neuromuscular disorder caused by a deficit in acid alpha-glucosidase. Macroglossia and swallowing disorders have already been reported, but no study has focused yet on its frequency and functional impact on patients' daily life. METHODS: We reviewed 100 adult LOPD patients followed in 17 hospitals in France included in the French national Pompe disease registry. The Swallowing Quality of Life Questionnaire and the Sydney Swallow Questionnaire were completed by patients, and a specialist carried out a medical examination focused on swallowing and assigned a Salassa score to each patient. Respiratory and motor functions were also recorded. Subgroup analysis compared patients with and without swallowing difficulties based on Salassa score. RESULTS: Thirty-two percent of patients presented with swallowing difficulties, often mild but sometimes severe enough to require percutaneous endoscopic gastrostomy (1%). Daily dysphagia was reported for 20% of our patients and aspirations for 18%; 9.5% were unable to eat away from home. Macroglossia was described in 18% of our patients, and 11% had lingual atrophy. Only 15% of patients presenting with swallowing disorders were followed by a speech therapist. Swallowing difficulties were significantly associated with macroglossia (p = 0.015), longer duration of illness (p = 0.032), and a lower body mass index (p = 0.047). CONCLUSIONS: Swallowing difficulties in LOPD are common and have significant functional impact. Increased awareness by physicians of these symptoms with systematic examination of the tongue and questions about swallowing can lead to appropriate multidisciplinary care with a speech therapist and dietitian if needed.