Idlir Licaj

L’objectif de la thèse est de mesurer en France l’influence des inégalités socioéconomiques individuelles et contextuelles sur la mobilité, l’incidence et la gravité des accidents corporels chez les enfants et les jeunes de moins de 25 ans. Des analyses originales sont effectuées à partir des bases de données suivantes : le Registre des Victimes d’accidents corporels de la circulation du Rhône, l’enquête ménage déplacement (EMD) de 2005-06 et une enquête épidémiologique de type cas-témoins réalisée durant la thèse. Excepté pour les victimes à deux-roues à moteur les incidences d’accidents lors de l’usage des différents modes de transports (voiture, vélo, marche et rollers) sont plus élevées chez les habitants des communes d’habitation défavorisées. Le sexe est également un facteur déterminant et très variable selon les modes de transport. L’effet de facteurs socioéconomiques sur la gravité des blessures d’accidents des jeunes, les différences socioéconomiques individuelles et contextuelles d’usage des modes de transports, de motorisation des ménages et d’accès au permis de conduire sont également étudiés. L’enquête de type cas témoins permet ensuite de pousser l’investigation en s’intéressant simultanément aux accidents, à la mobilité et à certains facteurs intermédiaires comme les comportements à risques (routier et non routiers) des jeunes. La reconnaissance des inégalités sociales de mobilité et d’accidents corporels peut permettre d’orienter les campagnes de prévention sur l’existence de zones et de groupes à risques

Aims/hypothesis: Teplizumab is approved in the USA and seven other countries to delay stage 3 type 1 diabetes onset in individuals ≥8 years of age with stage 2 type 1 diabetes. As part of a US Food and Drug Administration post-marketing requirement, this study evaluated the safety, tolerability and pharmacokinetics of teplizumab in children aged <8 years with stage 2 type 1 diabetes. Methods: The PETITE-T1D trial is a 2 year single-arm, open-label, multicentre study of 23 children <8 years of age with stage 2 type 1 diabetes. Participants received a 14 day teplizumab course. A prespecified interim analysis was performed after 15 participants completed 1 year of follow-up and included all 23 participants. Primary endpoints included treatment-emergent adverse events (TEAEs), TEAEs causing treatment discontinuation, and serious adverse events (SAEs). Other endpoints assessed immunogenicity, pharmacokinetics, pharmacodynamics and time from study treatment to stage 3 type 1 diabetes. Results: Mean participant age was 4.8 years (range 1.7–6.8). Median follow-up duration was 51.9 weeks (range 3.9–77.1). All participants experienced one or more TEAE, with most being mild to moderate. No grade 4 or 5 TEAEs were reported. Three participants (13%) had TEAEs leading to teplizumab discontinuation: anaemia, elevated liver enzymes and maculo-papular rash. Two participants (9%) each had two SAEs. Serum teplizumab concentrations peaked at day 14. Two participants progressed to stage 3 type 1 diabetes. The estimated probability of lack of progression to stage 3 was 89.6% (95% CI 64.3%, 97.3%) at the time of interim analysis. Conclusions/interpretation: Teplizumab was safe and well tolerated in children <8 years of age with stage 2 type 1 diabetes. Adverse events were consistent with those seen in previous studies, with no new safety risks identified. Two participants progressed to stage 3 type 1 diabetes during the observation period; surveillance is ongoing. Trial registration: ClinicalTrials.gov NCT05757713. Graphical

Background Work-related determinants of return to work (RTW) after breast cancer (BC) have been poorly studied. Methods We analysed data from 2095 patients with primary BC enrolled in the French multi-center prospective cohort CANTO between 2012 and 2018. We investigated the association between administrative, physical and psychosocial working conditions and RTW two years after diagnosis using Poisson regression with robust variance. All models were adjusted for age, education, having a partner or children, and clinical variables at diagnosis. Analyses stratified by education (up to/higher than high school) and by chemotherapy were conducted. Multiple imputations were performed. Results Having no weekly rest period of 48 consecutive hours (RR = 1.36 95% CI:1.09–1.81), strenuous work postures (RR = 1.48 95% CI:1.19–1.87) and shift work (RR = 1.40 95% CI:1.11–1.75) as well as low independence of decision making (RR = 1.33 95% CI:1.04–1.81) were associated with increased non-RTW. Not perceiving her own job as boring (RR = 0.61 95% CI:0.39–0.86) was associated with decreased non-RTW. Administrative working conditions did not impact RTW. Conclusion Working conditions emerged as potential levers to help women RTW. Our results underline the need for more targeted rehabilitation programs and personalized interventions to effectively help women in their RTW journey after BC.

Introduction Continuing medical education (CME) is essential for more than 100 million healthcare professionals worldwide, supporting enhancement of knowledge, skills, and patient outcomes. With a growing shift towards online and blended CME formats, expert-informed AI-based training (EIAT) is a novel e-training approach enabling rapid course creation and a timely content updates. However, its effectiveness remains underexplored. Methods A within-subject pre-post study was conducted with 17 medical students and professionals . Participants first completed a self-paced EIAT module, followed by live expert-led training (LET). Knowledge acquisition was measured via pre- and post-exams for each modality. Satisfaction, engagement, learning outcomes, and content quality were assessed using a 20-item CME-relevant feedback tool aligned with European Accreditation Council for CME standards. Paired t-test and McNemar’s tests were used to compare outcomes between the two training formats. Results EIAT completion was 76%, compared to 82% for LET. Pre-test scores were lower in LET (63 ± 11.4) than EIAT (73.8 ± 11.2), though not significantly different (p = 0.14). Mean knowledge gain was 17.3 ± 13.3 for EIAT (p = 0.0005) and 29.2 ± 13.2 for LET (p = 0.003), with no significant difference between modalities (mean difference 14.2 ± 21.5, p = 0.17) or in post-test scores (93.5 ± 5.5 vs. 93.3 ± 9.3, p = 0.79). Both formats achieved high satisfaction, with mean recommendation scores of 9.7 (SD = 0.67) for EIAT and 10 (SD = 0.0) for LET, respectively, and no significant differences across most evaluation domains (p > 0.05). Engagement was strong in both groups, though 71.4% of LET participants reported being ‘enthusiastically involved’ compared to 60% in EIAT, and 85.8% of LET participants gaining substantial practical knowledge versus 50% for EIAT (p = 0.08). Both formats were rated highly in terms of fairness, content quality, and absence of commercial bias. Conclusion: This pilot study provides preliminiary evidence that expert-informed AI is an effective alternative or complement to traditional live CME format. These findings offer further research into EIAT’s role in scalable, high-quality CME for healthcare professionals, laying the groundwork for future research and broader implementation.

Aims: We described the age-specific trajectories of total alcohol consumption and the consumption of different types of beverages among adult Norwegian women as they age, and how these relate to education, lifestyle, and health-related factors. Methods: This study included 76 382 women aged 31–70 years who participated in at least two of the three Norwegian Women and Cancer (NOWAC) study surveys conducted in 1991–97, 1998–2003, and 2004–11. Group-based trajectory modeling was used to identify the trajectories of self-reported alcohol consumption. Multinomial regression models were used to fit the adjusted odds ratios (ORs) of the associations between education, lifestyle, health-related factors, and the trajectory membership. Analysis was stratified into two subcohorts: women aged 31–49 years and women aged 50–70 years at enrolment. Results: Five different trajectories of total alcohol consumption were identified among the two subcohorts: non-drinker stable (12.5%–23.6%), low stable (66.3%–60.1%), light increasing or light unstable (17.8%–12.1%), moderate to high or light to high (2.8%–2.7%), and high to moderate or moderate decreasing (.6%–1.4%). Trajectories were resembled by those of wine consumption. Compared to low stable drinkers, women who sustained or increased their total alcohol consumption showed higher ORs for higher education level, excellent self-rated health, former or current smoking status, and a body mass index (BMI) below 25 kg/m2. Conclusion: While most women in this study maintained stable low-light levels of alcohol consumption, certain groups—such as women with higher education and better health—were more likely to increase their drinking with age. Women can particularly increase their drinking around the retirement age. The increasing trends of total alcohol consumption were reflected by those of wine. These findings provide information into groups and beverages that could be targeted in alcohol-reducing interventions.

Given the constant pressure to increase patient throughput while respecting radiation protection, global body PET image quality (IQ) is not satisfactory in all patients. We first studied the association between IQ and other variables, in particular body habitus, on a digital PET/CT. Second, to improve and homogenize IQ, we evaluated a deep learning PET denoising solution (Subtle PET^TM) using convolutional neural networks. We analysed retrospectively in 113 patients visual IQ (by a 5-point Likert score in two readers) and semi-quantitative IQ (by the coefficient of variation in the liver, CV_liv) as well as lesion detection and quantification in native and denoised PET. In native PET, visual and semi-quantitative IQ were lower in patients with larger body habitus (p < 0.0001 for both) and in men vs. women (p ≤ 0.03 for CV_liv). After PET denoising, visual IQ scores increased and became more homogeneous between patients (4.8 ± 0.3 in denoised vs. 3.6 ± 0.6 in native PET; p < 0.0001). CV_liv were lower in denoised PET than in native PET, 6.9 ± 0.9% vs. 12.2 ± 1.6%; p < 0.0001. The slope calculated by linear regression of CV_liv according to weight was significantly lower in denoised than in native PET (p = 0.0002), demonstrating more uniform CV_liv. Lesion concordance rate between both PET series was 369/371 (99.5%), with two lesions exclusively detected in native PET. SUV_max and SUV_peak of up to the five most intense native PET lesions per patient were lower in denoised PET (p < 0.001), with an average relative bias of −7.7% and −2.8%, respectively. DL-based PET denoising by Subtle PET^TM allowed [¹⁸F]FDG PET global image quality to be improved and homogenized, while maintaining satisfactory lesion detection and quantification. DL-based denoising may render body habitus adaptive PET protocols unnecessary, and pave the way for the improvement and homogenization of PET modalities.

Background: The authors used the French breast cancer Cancer and Toxicities (CANTO) cohort to study the associations between baseline quality of life and chemotherapy dose‐reductions (CDRs) or postchemotherapy‐toxicities (PCTs).Methods: In total, 3079 patients with breast cancer who received chemotherapy were included in this analysis. The associations between baseline physical functioning (PF) and fatigue measured using the European Organization for Research and Treatment of Cancer Quality‐of‐Life Questionnaire Core 30, and two endpoints—CDRs during adjuvant or neoadjuvant chemotherapy; and selected PCTs were estimated with odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) using logistic regression models.Results: Among the 3079 patients from the CANTO cohort who were included, 718 (33.0%) received chemotherapy in the neoadjuvant setting, and 2361 (67.0%) received chemotherapy as adjuvant treatment. The chemotherapy included taxanes in 94.2% of patients and anthracyclines in 90.5% of patients. Overall, 15.5% of patients experienced CDRs and, 31.0% developed PCTs. Women with low baseline PF scores (<83) had higher multivariate odds of developing CDRs compared with those who had PF scores ≥83 (OR, 1.54; 95% CI, 1.13–2.09). The corresponding OR for PCTs was 1.50 (95% CI, 1.13–2.00). Women with high baseline fatigue scores had higher odds of CDRs (OR, 1.43; 95% CI, 1.13–1.76) and PCTs (OR, 1.32; 95% CI, 1.10–1.59).Conclusions: By using the national CANTO cohort, baseline PF and fatigue were independently associated with CDRs and PCTs.

Older cancer patients are vulnerable to chemotherapy-related cognitive impairment. We prospectively evaluated cognitive impairment and its predictive factors during first-line chemotherapy in elderly cancer patients (≥70 years). Cognitive function was evaluated by the Mini-Mental State Examination (MMSE) with adjusted scores for age and sociocultural level. Multidimensional geriatric assessment was performed at baseline and during chemotherapy including the MMSE, Instrumental Activities in Daily Living (IADL), Mini-Nutritional Assessment (MNA), and the Geriatric Depression Scale (GDS15). Quality of life (QoL) was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ-C30). Of 364 patients included, 310 had two MMSE evaluations including one at baseline and were assessed. Among these patients, 86 (27.7%) had abnormal MMSE, 195 (62.9%) abnormal MNA, 223 (71.9%) abnormal IADL, and 137 (43.1%) had depressive symptoms at baseline. MMSE impairment during chemotherapy was observed in 58 (18.7%) patients. Abnormal baseline MNA (odds ratio (OR) = 1.87, p = 0.021) and MMSE (OR = 2.58, p = 0.022) were independent predictive factors of MMSE impairment. These results suggest that pre-existing cognitive impairment and malnutrition are predictive factors for cognitive decline during chemotherapy in elderly cancer patients. Detection and management of these risk factors should be systematically considered in this population before starting chemotherapy.

Purpose Thyroid cancer (TC) incidence is increasing. With its good prognosis and the young population concerned, the number of survivors is rising. However, their quality of life appears worse than expected. This study aims to assess the social and sexual health (SSH) of TC survivors and associated factors after a 2- and 5-year follow-up. Methods This study belongs to the National VICAN Survey implemented in France among TC patients diagnosed between January and June 2010. Data were collected via phone interviews, medical surveys, and from medico-administrative register in 2012 and 2015. We used multivariable logistic regressions to qualify TC impact on SSH. Results Across 146 patients, 121 were women, 50.7% were less than 42 years old, 77.5% were diagnosed at an early-stage, and 97.6% underwent thyroidectomy. At 2 years, 60.0% experienced social life discomfort because of cancer, 40.6% reported a decreased sexual desire, 37.4% fewer intercourse, 31.9% felt dissatisfied with this frequency, 30% reported difficulties achieving orgasm, and 15.2% considered that cancer had a negative influence for procreation. No significant difference was observed at 5 years. SSH was never discussed with medical professionals for 96.7% patients, as it was not proposed as a topic of concern (79.1%). In multivariable analysis, depression, embarrassment regarding their physical appearance since treatment, and reduced gestures of affection remained associated with decreased sexual desire. Conclusion This study highlights that TC is associated with an alteration of SSH which remains even at 5 years post-diagnosis. SSH should be discussed during diagnosis and considered during follow-up.