A realistic approach for evaluating antimicrobial surfaces for dry surface exposure scenarios.

The severe acute respiratory syndrome coronavirus 2 pandemic has raised public awareness about the importance of hygiene, leading to an increased demand for antimicrobial surfaces to minimize microbial contamination on high-touch surfaces. This is particularly relevant in public and private transportation settings, where surfaces frequently touched by individuals pose a significant, yet preventable, risk of infection transmission. Typically, the antimicrobial activity of surfaces is tested using test methods of the International Standards Organization, American Society for Testing and Materials, or Japanese Industrial Standards, which involve complete submersion in liquid, elevated temperature (37°C), and prolonged (24 h) contact periods. However, these conditions do not accurately represent real-world scenarios where surfaces are exposed to air. In this study, we propose a modified test method designed to better reflect real-life conditions in the intended end-use setting. The modifications included using deionized water instead of nutrient broth while preparing bacterial inoculum, applying a small test inoculum to the surface and allowing it to dry, maintaining ambient temperature and relative humidity throughout the contact period, and reducing the contact period to 4 h. With this modified approach, the antimicrobial activity of 20 samples was reassessed. This screening revealed that out of 20 samples, only 2 samples were effective against all species, while 8 samples demonstrated partial effectiveness against selected species, and 10 samples showed no significant effect. These findings highlight the inadequacy of the current test standard and emphasize the urgent necessity for revised and adapted testing method to ensure a reliable and accurate evaluation.IMPORTANCEThe recent severe acute respiratory syndrome coronavirus 2 pandemic has sparked increased demand for antimicrobial surfaces to mitigate the risk of fomites-transmitted infection in both indoors and confined spaces. Commonly, the antimicrobial activity of these surfaces is assessed using test standards established by national standards bodies, which do not distinguish between different application scenarios. While these test standards are suitable for surfaces intended for submerged application, they are inappropriate for antimicrobial surfaces designed for dry surface exposure. The usage of these standards can lead to an overestimation of antimicrobial efficacy. Thus, this study introduces a modified dry exposure test method aimed at better reflecting real-life conditions in the intended end-use setting. Our results revealed the subpar antimicrobial performance of numerous samples, highlighting the necessity to revise and tailor the universal test standard to real-world scenarios in order to ensure a reliable and accurate evaluation.

Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.

Cluster Analysis Identifies Patients With Severe Eosinophilic Asthma Who Achieve Super-Response and Remission With Mepolizumab.

This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies.

Interview Versus Performance Assessment of Cognition as Predictors of Real-World Outcomes in a Large-Scale Cross-Sectional Study in Schizophrenia.

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). It is approved as a coprimary measure of performance-based instruments, such as the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Recent research highlights negative symptoms, social cognition, and functional capacity as mediators of cognitive impairment's impact on functioning. This study compared mediation analysis outcomes using CAI or MCCB scores, providing insights into the utility of interview-based tools in research and clinical practice. The study included 618 individuals diagnosed with schizophrenia, recruited from 24 Italian psychiatric clinics. Neurocognitive assessments utilized both CAI and MCCB. Mediation analyses explored negative symptoms, social cognition, and functional capacity as mediators of the impact of neurocognition on real-life functioning domains. The study's results extend the validation of the CAI as a coprimary measure that provides valid information on the impact of cognitive impairment on real-life functioning and its possible mediators, complementing the information obtained using the MCCB. Interview-based cognitive assessment might be essential for understanding schizophrenia complexity and its impact on various cognitive and functional domains for clinicians, patients, and caregivers.

Real-World Study of Ragweed Sublingual Immunotherapy in Hungary.

BACKGROUND: Ragweed (Ambrosia elatior) has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest. OBJECTIVE: This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen. METHODS: We retrospectively reviewed the clinical records of 57 patients during the 2015 and 2016 ragweed pollen seasons. Patients were divided into two groups: Group 1 (n = 29), who had not received immunotherapy, and Group 2 (n = 28), who had previously undergone immunotherapy with another sublingual preparation. All patients were treated with Oraltek® ragweed for 4-6 months, initiating 2-4 months before the pollen season and rest of the period was 2 months of the 2016 pollen season. Symptom score (SS), medication score (MS), and combined symptom and medication score (CSMS) were evaluated intra- and intergroup. RESULTS: Pollen counts were consistent between 2015 and 2016. All patients showed significant improvement in SS, MS, and CSMS, with a large effect size (>0.8). Group 2 had significantly lower SS and CSMS in 2015 because of prior immunotherapy. By 2016, both groups exhibited marked improvements, with Group 1 showing a 75% improvement in CSMS. No local or systemic reactions were recorded, indicating a high safety profile. CONCLUSIONS: Ragweed SLIT significantly improved symptoms and reduced use of medication in patients allergic to ragweed pollen. The treatment was effective even in patients with previous immunotherapy, with a high benefit-risk ratio demonstrated by the absence of adverse reactions. These findings support the use of Oraltek SLIT for managing ragweed pollen allergy.

Radiological evaluation of response in patients with locally advanced/metastatic soft tissue sarcoma treated with trabectedin.

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32-78). The median number of trabectedin cycles administered was four (range 2-50) for a median follow up of 5.83 months (range 1-60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7-4.6); median overall survival was 34.3 months (CI95% 0-75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen's kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.

Calcitonin Gene-Related Peptide Monoclonal Antibodies: Key Lessons from Real-World Evidence.

BACKGROUND: The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. OBJECTIVE: This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. METHODS: We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. RESULTS: Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. CONCLUSIONS: Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology.

Response predictors of a topical corticosteroid-based regimen for dry eyes: A real-life study.

PURPOSE: To examine the effectiveness and identify clinical response predictors of a short corticosteroid-based regimen consisting of topical preservative-free 0.1% dexamethasone (Monopex®, Théa Laboratories) in conjunction with artificial tears (AT) for dry eyes in a real-life clinical setting. METHODS: Patients were recruited from the Norwegian Dry Eye Clinic and were allowed to use ATs of their own choice in addition to the prescribed 14-day topical dexamethasone course. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire (DEQ-5), Schirmer test (ST), fluorescein tear film break-up time (FBUT), ocular surface staining (OSS), meibum expressibility (ME), meibum quality (MQ), number of expressible meibomian glands among the central eight glands in the lower lids (NMG) and intraocular pressure (IOP) were measured at baseline and at 1-month follow-up. The average values of clinical parameters from both eyes were used for analyses. A paired t-test and a significance value of p < 0.05 were used for statistical analyses. Associations between sex, age, baseline values and the changes after the intervention (Δ) were explored using linear regression. RESULTS: A total of 167 patients (124 women, mean age 54 years ±17 (standard deviation)) were included. One month after initiation of intervention, OSDI and DEQ5 scores improved from 39.5 ± 22.1 to 31.4 ± 21.3 (p < 0.001) and from 12.6 ± 4.2 to 11.0 ± 4.6 (p < 0.001), respectively. OSS improved from 2.2 ± 1.4 to 1.8 ± 1.5 (p < 0.001), NMG increased from 4.8 ± 2.2 to 5.1 ± 2.2 (p < 0.05), while IOP decreased from 12.9 ± 3.3 to 12.4 ± 3.5 mmHg (p < 0.05). Significant associations were found between the change in symptoms and objective measures of DED (ΔOSDI, ΔDEQ5, ΔOSS, ΔFBUT, ΔNMG, ΔMQ) and their respective baseline values (OSDI, DEQ5, OSS, FBUT, NMG, MQ). The remaining tests did not show statistically significant changes. CONCLUSION: Improvement in dry eye symptoms and signs were observed following a short course of topical, preservative-free 0.1% dexamethasone treatment in combination with AT. Individuals exhibiting more pronounced symptoms and signs witnessed the most profound improvements with the treatment regimen, suggesting that poor baseline parameters may serve as response predictors of the treatment regimen. While the real-life data presented herein are valuable, the conclusions are limited by the inherent biases of a non-controlled study.

Elderly patients with venous thromboembolism: Insights from the RIETE registry.

Venous thromboembolism (VTE) presents a notable healthcare burden, particularly among the elderly, who experience increased risks and more severe complications. This review aims to use the extensive data from the RIETE registry, a comprehensive database on consecutive patients with VTE. We examine the clinical features, therapeutic approaches, and patient outcomes of VTE in elderly patients, compared to younger patients, offering a comprehensive understanding of management challenges and emphasizing the need for strategies that accommodate the unique challenges of this population.

Personalized sleep and nutritional strategies to combat adverse effects of night shift work: a controlled intervention protocol.

BACKGROUND: Working during the night interferes with the timing of normal daily activities and is associated with an increased risk of chronic diseases. Under controlled experimental conditions, interventions focusing on sleep and nutrition can mitigate the short-term adverse effects of shift work. However, it is unclear how these results translate to real-life, how they can be targeted to individual conditions, and how they relate to long-term health. Therefore, the current study aims to implement a personalized sleep and nutritional intervention among night shift workers in the field. METHODS: A non-blinded controlled intervention study is used, consisting of a run-in period, an intervention of 3 months, post-intervention measurements, and a follow-up after 12 months. Three study arms are included: sleep intervention, nutritional intervention, and control group (n = 25 each). Participants are healthy 18-60-year male night shift workers, with at least one year of experience in night shift work. Information from the run-in period will be used to personalize the interventions. The main outcomes are sleep measurements and continuous interstitial glucose levels. Furthermore, general health biomarkers and parameters will be determined to further evaluate effects on long-term health. DISCUSSION: This study aims to mitigate negative health consequences associated with night shift work by introducing two personalized preventive interventions. If proven effective, the personalized interventions may serve as practical solutions that can have a meaningful impact on the sustainable health and employability of night shift workers. This study will thereby contribute to the current need for high-quality data on preventative strategies for night shift work in a real-life context. TRIAL REGISTRATION: This trial has been registered under ClinicalTrials.gov Identifier NCT06147089. Registered 27 November 2023.

Real-Life Use of Automated Insulin Delivery in Individuals With Type 2 Diabetes.

BACKGROUND: The objective of this work is to document performance of automated insulin delivery (AID) during real-life use in type 2 diabetes (T2D). METHODS: A retrospective analysis was performed of continuous glucose monitoring and insulin delivery data from 796 individuals with T2D, who transitioned from 1-month predictive low-glucose suspend (PLGS) use to 3-month AID use, in real-life settings. Primary outcome was change of time in range (TIR = 70-180 mg/dL) from PLGS to AID. Secondary outcomes included time above/below range (TAR/TBR) and total daily insulin (TDI). RESULTS: Compared with PLGS, AID increased TIR on average from 63.2% to 72.6%, decreased TAR from 36.2% to 26.8%, and increased TDI from 70.2 to 76.3 U (all P < .001), without significant change to TBR. Glycemic improvements were more pronounced in those with worse glycemic control during PLGS use (P < .001). CONCLUSIONS: Real-life use of AID led to a rapid and sustained improvement of glycemic control in individuals with T2D.

Evaluation of a New Telemedicine System for Early Detection of Cardiac Instability in Patients With Chronic Heart Failure: Real-Life Out-of-Hospital Study.

BACKGROUND: For a decade, despite results from many studies, telemedicine systems have suffered from a lack of recommendations for chronic heart failure (CHF) care because of variable study results. Another limitation is the hospital-based architecture of most telemedicine systems. Some systems use an algorithm based on daily weight, transcutaneous oxygen measurement, and heart rate to detect and treat acute heart failure (AHF) in patients with CHF as early on as possible. OBJECTIVE: The aim of this study is to determine the efficacy of a telemonitoring system in detecting clinical destabilization in real-life settings (out-of-hospital management) without generating too many false positive alerts. METHODS: All patients self-monitoring at home using the system after a congestive AHF event treated at a cardiology clinic in France between March 2020 and March 2021 with at least 75% compliance on daily measurements were included retrospectively. New-onset AHF was defined by the presence of at least 1 of the following criteria: transcutaneous oxygen saturation loss, defined as a transcutaneous oxygen measurement under 90%; rise of cardiac frequency above 110 beats per minute; weight gain of at least 2 kg; and symptoms of congestive AHF, described over the phone. An AHF alert was generated when the criteria reached our definition of new-onset acute congestive heart failure (HF). RESULTS: A total of 111 consecutive patients (n=70 men) with a median age of 76.60 (IQR 69.5-83.4) years receiving the telemonitoring system were included. Thirty-nine patients (35.1%) reached the HF warning level, and 28 patients (25%) had confirmed HF destabilization during follow-up. No patient had AHF without being detected by the telemonitoring system. Among incorrect AHF alerts (n=11), 5 patients (45%) had taken inaccurate measurements, 3 patients (27%) had supraventricular arrhythmia, 1 patient (9%) had a pulmonary bacterial infection, and 1 patient (9%) contracted COVID-19. A weight gain of at least 2 kg within 4 days was significantly associated with a correct AHF alert (P=.004), and a heart rate of more than 110 beats per minute was more significantly associated with an incorrect AHF alert (P=.007). CONCLUSIONS: This single-center study highlighted the efficacy of the telemedicine system in detecting and quickly treating cardiac instability complicating the course of CHF by detecting new-onset AHF as well as supraventricular arrhythmia, thus helping cardiologists provide better follow-up to ambulatory patients.

A 3-Year Experience with Tildrakizumab Treatment for Patients with Plaque Psoriasis in Clinical Practice.

INTRODUCTION: The efficacy and safety of tildrakizumab for the treatment of plaque psoriasis were demonstrated by randomized clinical studies, but the reappraisal of prolonged experiences in the clinical practice helps to optimize the use of this biologic drug. The aim of this study was to evaluate the long-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the real world. METHODS: This is a long-term retrospective observational study in a real-life setting. Overall, 136 adult patients with moderate-to-severe plaque psoriasis and treated with tildrakizumab were included. RESULTS: One hundred percent reduction of Psoriasis Area Severity Index (PASI100) was reached by 21.7% of patients at 4 weeks of therapy and by 51.2% at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We could not confirm a previous observation that patients naïve to biologic had a better response, but we observed that those with a short history of psoriasis had a higher probability of 90% PASI reduction (PASI90) or PASI 100 within 36 weeks, suggesting that early treatment could be useful. CONCLUSION: This long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years.

SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma.

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06-30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24-14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04-1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71-76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10-19-NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58-91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7-75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16-73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

Does the PedsQL reflect the real-time quality of life in autistic adolescents? A comparison with the experience sampling methodology.

BACKGROUND: The PedsQL is widely used to retrospectively evaluate quality of life (QoL) in autistic adolescents. However, concerns have arisen regarding its ability to reflect real-time QoL, considering their challenges in recollecting past experiences. OBJECTIVE: We examined the overall and social QoLs of autistic adolescents compared to neurotypical peers using the PedsQL and the experience sampling method (ESM), an ecological momentary assessment of QoL in real-time. Additionally, we explored the relationship between these measures in each group. METHODS: A total of 175 participants, including 117 autistic and 58 neurotypical adolescents aged 10-16, completed the PedsQL and an ESM protocol with a mobile device to record their real-time experiences seven times a day for seven days. We performed multiple linear regression and multilevel analyses to compare QoLs between groups and the association between the two measures. RESULTS: Autistic adolescents scored significantly lower than neurotypical peers on PedsQL overall and social QoL but not on the real-time experiences collected with ESM. Among neurotypical adolescents, we found significant associations between the Social Functioning score of the PedsQL and various aspects of real-time social experiences recorded with ESM. For autistic adolescents, only the real-time experience of 'loneliness' during social engagement was associated with Social Functioning on the PedsQL. CONCLUSIONS: The retrospective PedsQL does not entirely capture the real-time QoL via ESM. However, relying solely on ESM may overlook situations where participants opt out or could not complete surveys. Thus, using both retrospective and real-time assessments to examine QoL among autistic adolescents is recommended.

Coordination and Referral Platforms for Children Aged 7 and Under with Suspected Neurodevelopmental Outcome: What Data for Research on Care and Developmental Trajectories?

At the core of the child's medical, social, and educational pathway, coordination and referral platforms (CRPs) for neurodevelopmental disorders (NDDs) have been gradually deployed in France since 2018 and support the early detection of NDDs in children. The 112 nationwide CRPs do not benefit from a common electronic health record system. Our aim was to propose an HER model for CRP to enable real-life data reuse, optimize care pathway management and conduct pre-screening for research. CRP data were collected (n=34) into an application enriched by a NLP tool extracting standardized scales for NDDs assessments from medical and paramedical professionals. NLP tool evaluation presented a precision of 86.4% and recall of 90.5%. CRP support was provided to 195 children included between 1 September 2022 and 31 August 2023, aged 4 years, with a sex ratio of 2.8, with delays reported in language (75%) and concerned by global developmental delays (16%). Children's ND phenotype and care pathway description could be automated by a harmonized and structured EHR. While many clinical situations are at an impasse, real-life data-driven evidence is particularly relevant in the context of NDDs, where early intervention plays such a key role in children's development and prognosis. A harmonized and enriched CRP database could benefit both individual and public health levels with pathway monitoring, intervention proposals and research pre-screenings.

Optimizing Data Extraction: Harnessing RAG and LLMs for German Medical Documents.

In the field of medical data analysis, converting unstructured text documents into a structured format suitable for further use is a significant challenge. This study introduces an automated local deployed data privacy secure pipeline that uses open-source Large Language Models (LLMs) with Retrieval-Augmented Generation (RAG) architecture to convert medical German language documents with sensitive health-related information into a structured format. Testing on a proprietary dataset of 800 unstructured original medical reports demonstrated an accuracy of up to 90% in data extraction of the pipeline compared to data extracted manually by physicians and medical students. This highlights the pipeline's potential as a valuable tool for efficiently extracting relevant data from unstructured sources.

Real-World Survival Impact of New Treatment Strategies for Lung Cancer: A 2000-2020 French Cohort.

Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all patients consecutively treated at Institute Curie for metastatic lung cancer. Diagnosis date was used to define three periods, based on the approvals of novel treatment strategies in the first-line setting, including targeted therapies in 2010 and immunotherapy in 2018. Endpoints included Overall survival (OS), survival rate of 2 years and 5 years, and a conditional survival rate of 2 years (if still alive at 6 months from treatment initiation). A total of 673 patients were identified for Period 1-2000 to 2009, 752 for Period 2-2010 to 2017, and 768 for Period 3-2018 to 2020. Median OS in the whole cohort was 11.1, 15.5, and 16.2 months, respectively. Median OS for patients with NSCLC or SCLC was 11.2, 17.2, and 18.2 months, or 10.9, 11.7, and 11.2 months, respectively. The two-year conditional survival was more favorable for NSCLC than SCLC patients. Outcomes were statistically higher for women as compared to men in all periods and all subgroups. Survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC, along with the implementation of novel treatment strategies.

How comparative studies can inform treatment decisions for Crohn's disease.

INTRODUCTION: As new therapies for the treatment of Crohn's disease (CD) are approved, there is an increasing need for evidence that clarifies their positioning and sequencing. AREAS COVERED: Comparative effectiveness research (CER) aims to inform physicians' decisions when they choose which intervention (drug or treatment strategy) to administer to their patients. Pragmatic head-to-head trials represent the best tools for CER, but only a few have been published in the IBD field. Network meta-analyses can point toward the superiority of one drug over another, but they do not reflect everyday clinical practice. Finally, real-world evidence complements that coming from head-to-head trials and network meta-analyses, assessing the real-life effectiveness of therapeutic interventions. EXPERT OPINION: There is insufficient evidence to create a definitive therapeutic algorithm for CD, but some general considerations can be made. Anti-TNF-α agents seemingly represent the most 'sustainable' first-line choice, considering benefit-harm ratio and costs; vedolizumab, ustekinumab, and risankizumab may be considered as first-line choice when safety issues become prominent. In the event of pharmacodynamic failure, out-of-class swap is to be preferred - possibly with anti-IL23p19 as the best option, with unclear data regarding upadacitinib positioning; a second anti-TNF-α could be considered, as a second choice, after pharmacokinetic failure.