French Patients Research Articles

Exploring the limitations of language interpretation: A qualitative study on clinicians' experiences at French Office of Immigration and Integration.

The concordance of communication between patients and health professionals is essential to promoting positive health outcomes. However, concordance may be broken where language barriers exist therefore creating a need to use interpretation services. This is the case when rapid diagnostic testing (RDT) of HIV, HBV, and HCV is offered to migrants. The use of interpreters to establish communication with patients having limited French proficiency (LFP) however, is often not used and can be problematic. Despite being offered, interpretation services are frequently underutilised, which makes communication challenging. This problem has not received enough attention in the literature, particularly in a technologically advanced setting where solutions may be found. Our objective was to explore how interpreters are used within the context of medical consultations when RDT for HIV, HBV, and HCV is offered to legal migrants with LFP. A cross-sectional qualitative study was used with a purposive sample that included doctors and nurses who had conducted rapid screening tests with migrants in four centers in France and who had access to interpretive services. Semi-structured interviews explored healthcare providers' (HP) use of interpreters at the OFII. The use of professional or ad hoc interpreters, telephone interpreters, and the equivalence of concepts such as health literacy between the HP and the interpreter were explored. The utility of a new tool to promote communication concordance was evaluated. Twenty interviews were conducted with eleven doctors and nine nurses with a median age of 58 years (25-67 years). All participants had access to interpretive services although many did not solicit them because of 1) unawareness on how to use the services, 2) preconceived notions of the length of time to involve an interpreter and how this would add to consultation times, or 3) the proximity of an ad hoc interpreter. Not using interpreter services could result in RDTs not being offered to immigrants. Subjects such as confidentiality, the embarrassment of a third party's presence, the lack of appropriate training and differing levels of health literacy were also discussed by participants. Insight from HPs allows us to better understand how both telephone and in-person interpretation are used, viewed, and why they are underused to communicate with limited French language skills patients. Our findings will help us develop a conceptual model for a digital communication tool to overcome barriers with migrant patients with limited French language skills.

Perspectives and perception of haemophilia gene therapy by French patients.

A national survey was initiated by representatives of French patients with haemophilia (AFH) and the French reference centre for haemophilia, in order to appreciate the awareness and knowledge of these patients regarding haemophilia gene therapy (HGT) and understand better their position about this innovative treatment that will soon become available. Of 143 answers received, 137 could be analysed, representing about 3.5% of patients with severe or moderate haemophilia over 16year-old. They were 80.3% with haemophilia A and 19.7 % with haemophilia B, with a severe form of the disease for 80.3 % of them. Curiosity for HGT was formulated by 64.2% of the participants, 33.6 % being interested by this approach as soon as it will be available and 38.7 % preferring to wait until more patients have been treated. Only 3.6 % of the participants would never consider receiving HGT. The level of awareness and knowledge was estimated to be limited by 39.5 % of the patients. More than 60 % of them declared having never or almost never discussed HGT with the team of their haemophilia centre. Before deciding to get HGT, 54.4 % of the participants considered that it will be very important to compare it with their current treatment and 53.7 % would like to be better informed by their care providers. These results highlight the need for training and education for patients, but also for professionals at haemophilia centres, about HGT and the shared decision-making process. Objective, unbiased and transparent information must be available for patients about this very promising therapy which nonetheless carries more uncertainty and unknowns compared to other haemophilia treatments.

OP09 Developing A Patient And Consumer Training Tool Explaining Health Technology Assessment And Patient/Consumer Participation: The French Experience

IntroductionThe French National Authority for Health’s (HAS) 2019-2024 strategic workplan called for “making public involvement a priority.” This project was designed within the roadmap validated in 2021; “Strengthening public involvement in health technology assessment (HTA) at the HAS”, including an action of building a means of training patient organizations for their contribution. The project’s overall objective was to develop with patients and consumers a first training tool, representing an online knowledge base targeting French patients and consumers to explain the HAS HTA process and assist their participation in these assessments.MethodsThree stages were designed to meet this objective. Firstly, an international benchmark was performed of available online HTA training tools for patients and consumers, notably those used by HTA bodies and European and international patient and consumer groups (PCGs). Secondly, an internal HAS search for e-learning tools, was conducted to identify whether they could meet the training needs of French patients and consumers. Finally, the training tool was developed via a working group composed of patients and HAS scientific officers.ResultsThe benchmark identified 82 online training tools selected according to the specified inclusion criteria. Sixteen international HTA agencies, nine European and international PCGs and 13 other bodies provided online HTA training tools for patients and consumers during the research period, but no journal articles identified such tools. Eleven formats and 12 key themes, divided into two main categories were identified: important content related to HTA, and important content related to public involvement in HTA. The HAS search for e-learning tools resulted in internal e-learning tools offered for clinical experts not meeting the needs and preferences of patients and consumers. Finally, HAS based its training tool development on these preferences and needs to create a PowerPoint in two blocks of modules covering the two main categories above (six modules in total).ConclusionsFrench patients and consumers preferences and needs for a HTA training tool were inspired by the international benchmark, dividing key themes into two main categories: important content related to HTA, and important content related to public involvement in HTA. This resulted in HAS development of two blocks of modules in PowerPoint format covering these two categories.

OP08 International Benchmarking Of Health Technology Assessment Training Tools And Materials For Patients And Consumers

IntroductionThe objective was to conduct a benchmarking study of available online health technology assessment (HTA) training tools for patients, specifically those used by HTA agencies and major European and international patient and consumer groups (PCGs). We compared existing online training tools on this topic in order to develop in-house HTA training tools for French patients and consumers.MethodsA literature search and a scoping review of websites was conducted by including the websites of HTA agencies, European and international PCGs, and other bodies. This was supplemented with videoconference interviews with selected HTA agencies and patient groups. The inclusion criterion was the existence of content describing HTA and patient and public involvement (PPI) in HTA that PCGs could use (regardless of its format).ResultsEighty-two online training tools were selected according to the specified inclusion criterion. Sixteen international HTA bodies, nine European and international PCGs, and 13 other bodies provided online HTA training tools available for patients and consumers. No journal articles matching the inclusion criterion were found. Two broad categories of content were identified: the first relating to HTA and the second relating to PPI in HTA. Moreover, the formats of these tools ranged from interactive to non-interactive, with varying accessibility (freely available or with a paywall) and assessment methods.ConclusionsThese results should be considered together with budget requirements, project time constraints, human resources, and the preferences of HAS and patients when developing HTA training tools to improve the participation of patients and consumers in the HTA process at HAS.

Patient and Physician Perspectives on the Use of a Connected Ecosystem for Diabetes Management: International Cross-Sectional Observational Study.

Collaboration between people with type 2 diabetes (T2DM) and their health care teams is important for optimal control of the disease and outcomes. Digital technologies could potentially tie together several health care-related devices and platforms into connected ecosystems (CES), but attitudes about CES are unknown. We surveyed convenience samples of patients and physicians to better understand which patient characteristics are associated with higher likelihoods of (1) participating in a potential CES program, as self-reported by patients with T2DM and (2) clinical benefit from participation in a potential CES program, as reported by physicians. Adults self-reporting a diagnosis of T2DM and current insulin use (n=197), and 33 physicians whose practices included ≥20% of such patients, were enrolled in the United States, France, and Germany. We surveyed both groups about the likelihood of patient participation in a CES. We then examined the associations between patients' clinical and sociodemographic characteristics and this likelihood. We also described characteristics of patients likely to clinically benefit from CES use, according to physicians. Compared with patients in Germany and France, US patients were younger (mean age 45.3 [SD 11.9] years vs 61.9 [SD 9.2] and 65.8 [SD 9.4] years, respectively), more often female, more highly educated, and more often working full-time. In all, 51 (44.7%) US patients, 16 (36.4%) German patients, and 18 (46.3%) French patients indicated strong interest in a CES program, and 115 (78.7%) reported currently using ≥1 connected device or app. However, physicians believed that only 11.3%-19.2% of their patients were using connected devices or apps to manage their disease. Physicians also reported infrequently recommending or prescribing connected devices to their patients, although ≥80% (n=28) of them thought that a CES could help support their patients in managing their disease. The factors most predictive of patient likelihood of participating in a CES program were cost, inclusion of medication reminders, and linking blood glucose levels to behaviors such as eating and exercise. In all countries, the most common patient expectations for a CES program were that it could help them eat more healthfully, increase their physical activity, increase their understanding of how blood glucose relates to behavior such as exercise and eating, and reduce stress. Physicians thought that newly diagnosed patients, sicker patients-those who had been hospitalized for diabetes, were currently using insulin, or who had any comorbid condition-and patients who were nonadherent to treatment were most likely to benefit from CES use. In this study, there was a high degree of interest in the future use of CES, although additional education is needed among both patients with T2DM and their physicians to achieve the full potential of such systems to improve self-management and clinical care for the disease.

Circulating Tumor DNA (ctDNA) for Plasma Genotyping and Disease Monitoring in ALK-Positive Anaplastic Lymphoma (ALK+ALCL): A Proof of Concept Study

Introduction Circulating tumor DNA (ctDNA) detection has not been reported yet in ALK-positive anaplastic large cell lymphoma (ALK+ALCL), a rare aggressive non-Hodgkin lymphoma with a peak incidence in children, adolescents and young adults. In this study, we aimed to evaluate whether ctDNA can be detected, characterized and used to monitor minimal residual disease (MRD) in ALK+ALCL. Patients and Methods Plasma samples were collected from 23 French patients diagnosed with ALK+ALCL between November 2020 and March 2023. Based on cell-free DNA (cfDNA) extracted from plasma, we performed shallow whole genome sequencing (shWGS) and a comprehensive genomic profiling (CGP) of more than 500 genes covered at a median depth of over 3000 unique reads to assess ctDNA content. In this study, we defined samples as positive if they had a tumor fraction over 3%, evaluated by shWGS analysis, or if ALK rearrangements were identified using CGP. Additionally, ALK rearrangement genomic breakpoint were defined by CGP analysis. For each patient, specific digital droplet PCR (ddPCR) assays were designed based on the identified breakpoints to monitor ctDNA content during the ALK+ALCL disease follow-up. Results The median age of patients at the time of diagnosis was 13 years (range: 4-54). Sixteen patients, (69.6%) received at least one ALK tyrosine kinase inhibitor (TKI). A total of 80 plasma samples were collected at various time points from the 23 patients, with a median of 3 samples per patient (range: 1 - 20). Four samples failed for DNA extraction, resulting in 76 samples available for molecular analysis Of the 76 samples, 43 (56.6%) were analyzed using shWGS, 19 (25%) using CGP among which, 14 were analyzed using both techniques. CGP was found to be a more sensitive method for detecting ctDNA in ALK+ALCL compared to shWGS, with 12 out of 14 samples (85.7%) tested positive with CGP, compared to 5 out of 14 samples (35.7%) with shWGS (p<0.01). Of the 19 samples tested with CGP, ALK rearrangement was identified in 14 samples (73.7%), with NPM1:: ALK fusion detected in 11 samples, and ATIC:: ALK, TRAF1:: ALK and EEF1G:: ALK detected in one sample each. The average tumor mutational burden was low, with 5.3 mutations per megabase (mut/Mb) (range: 0-14.5 mut/Mb). No microsatellite instability was detected. Amplification of MDM4 and MYC genes was observed in three patients each. ANKRD26 was the most frequently mutated gene in the study, with four patients affected. LRP1B, epigenetic modifiers such as EP300 and KMT2A, and TP53 were mutated in three patients each. Interestingly, CGP allowed the identification of the ALK:c.3520T>C;p.(Phe1174Leu) mutation in a plasma sample collected during disease progression while the patient was on long lasting crizotinib therapy. Finally, we monitored MRD, based on ctDNA detection in 49 samples from 12 patients using ddPCR assays. Our results were compared with the established gold standard for MRD monitoring in ALK+ALCL, i.e. RT-PCR on circulating cells performed on the same samples. The ddPCR assay showed a 87% sensitivity, 100% specificity, 100% positive predictive value, and 83% negative predictive value. However, four samples had false-negative results due to pre-analytical sampling issues. These samples had been stored at room temperature without undergoing centrifugation for more than 24 hours. Conclusion To date, this study is the first to report on the feasibility and clinical value of ctDNA for the management of ALK+ALCL patients. CGP demonstrated high sensitivity in detecting ctDNA, identifying the genomic breakpoint within the ALK gene and, for the first time in ALK+ALCL, detecting resistance mutations to ALK TKI. Additionally, our unique patient-specific ddPCR approach was proven to be a cost-effective method for MRD monitoring. Altogether, these findings serve as a proof-of-concept for the development of ctDNA techniques in the clinical management of ALK+ALCL.

Standard modifiable risk factors and mortality in patients with ST-segment elevation myocardial infarction: findings from the FRENCHIE cohort

Abstract Background Improvements in the treatment of the 4 main standard modifiable cardiovascular (CV) risk factors (SMuRFs), hypertension (HTN), diabetes, hypercholesterolemia, and smoking, have led to better survival in patients with acute myocardial infarction (AMI). Recent large observational studies have reported that an increasing and sizable proportion of AMI patients have no SMuRF, and these SMURFless patients have (counterintuitively) worse outcomes than patients with at least one SMuRF. Purpose Using a French nationwide MI registry, we aimed to describe the proportion, characteristics and in-hospital mortality of ST-segment elevation MI (STEMI) patients according to the burden of SMuRFs. Methods The French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing MI cohort, which collects data from all patients hospitalized for AMI < 48 h of symptom onset in 21 french centres. For the present analysis, patients with STEMI and without prior coronary artery disease (CAD) admitted in 2019 and 2020 were studied. SMuRFless patients were compared to patients with 1 SMuRF or ≥2 SMuRFs. Results Among 4692 STEMI patients, 986(21%) were SMuRFless, 2001(43%) had 1 SMuRF, and 1705(36%) had ≥2 SMuRFs . Among patients with SMuRFs, smoking (51.8%) and HTN (51.1%) were the most frequent SMuRF and HTN+hypercholesterolemia (10.3%) and HTN+smoking (8.3%) the most frequent SMuRFs associations. When compared with patients with 1 or ≥ 2 SMuRFs, SMuRFless patients were characterized by older age (64.1 vs 60.2 and 62.8 y, respectively), but lower rate of female sex (21.7 vs 22.2 and 26.2%, respectively), LVEF<40% (24.5 vs 26.7 and 26.2%), and lower admission CRP (14.8±38.3 vs 15.3±38.7 and 17.3±40.1 mg/L, respectively). There was a slight increase in BMI with increasing SMURFs (0 SMURF : 26±3.9 ; 1 SMuRF : 26.3±4.5 ; ≥2 SMuRFs : 28.0±5 kg/m²). As expected, SMuRFless patients were less frequently under chronic CV medications (7.9 vs 23.5 and 57.7%, respectively). However, acute STEMI medications were similar across the 3 groups. Crude in-hospital mortality showed a trend toward an increase with the number of SMuRFs (p = 0.123). By multivariate logistic regression analysis, the number of SMURFs was associated with increasing in-hospital mortality (Figure). In stratified analyses, the odds were similar for both sexes. Conclusion In French patients with an inaugural STEMI, one in 5 patient was SMURFless. The burden of risk factors was independently correlated to worse in-hospital survival. These observations emphasize the importance of standard RF on acute MI outcomes.SMuRF and in-hospital death(forest plot)

One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: results of the French FHU INOVPAIN registry study

BackgroundRandomized clinical trials have demonstrated efficacy and safety of erenumab. The aim of this study is to evaluate the effectiveness and safety of erenumab in a real-world setting in French patients with migraine associated with extreme unmet needs.MethodsThis is a one year-prospective real-word study with enrolment of all consecutive adult patients included in the FHU InovPain registry who participated in a compassionate erenumab use program.ResultsOf 144 patients included, 140 patients (82.1% female / mean age of 50.9 ± 11.4) received at least one dose of erenumab and were concerned by effectiveness and safety assessment. All patients had failed 11 oral preventive treatments. Most of them suffered from chronic migraine (88.6%) and presented a medication overuse (90.7%) at baseline. Thirty-eight (27.1%) discontinued treatment during the 12-month follow-up, with 22 (15.7%), 11 (7.9%) and 5 (3.6%) patients before 3, 6 or 9 months of treatment. The proportion of ≥ 50% responders at M3, M6, M9 and M12 was 74/140 (52.9%), 69/118 (58.5%), 61/107 (57.0%) and 60/102 (58.8%) respectively. At M3, the rate of reversion from chronic migraine to episodic migraine was 57.3% and the rate of transition from medication overuse to non-overuse was 46.5%. For monthly migraine days, the median (IQR) was 18.0 (13.0–26.0), 9.0 (5.0–17.0), 7.5 (5.0–14.0), 8.0 (5.0–12.5) and 8.0 (5.0–12.0) at M0, M3, M6, M9 and M12 respectively. For HIT-6 score, the median (IQR) was 68.0 (63.8–73.3), 60.0 (54.0–65.0), 60.0 (50.3–53.0), 59.0 (50.0–63.0) and 58.0 (50.0–62.9) at M0, M3, M6, M9 and M12 respectively. Fifty-three (37.9%) patients reported at least one of the following adverse events: cutaneous erythema and/or pain at the injection site for 42 (30%) patients, constipation for 22 (15.7%) patients, muscle spasm for 2 (1.4%) patients, alopecia for one (0.7%) patient and blood pressure increase in one (0.7%) patient. There was no serious adverse event. One female patient became pregnant after 5 months of exposure to erenumab with a safe evolution after treatment discontinuation.ConclusionThis first French real-world study related to migraine prevention with CGRP-mAbs confirms effectiveness and safety of erenumab in patients with extreme unmet needs.

Editor's Choice -- Survival, Limb Salvage, and Management of Patients with Lower Limb Acute Ischaemia: A French National Retrospective Observational Study

The aim was to describe the baseline characteristics of French patients referred with acute limb ischaemia (ALI), and their clinical management and outcome (death, amputation). This retrospective observational cohort study used the National Health Data System. All adults hospitalised for ALI who underwent revascularisation with an endovascular or open surgical approach between 1 January 2015 and 31 December 2020 were included and followed up until death or the end of the study (31 December 2021). A one year look back period was used to capture patients' medical history. The risks of death, and major and minor amputations were described using Kaplan-Meier and Aalen-Johansen estimators. A Cox model was used to report the adjusted association between groups and risk of death and Fine-Gray models for the risk of amputations considering the competing risk of death. Overall, 51 390 patients (median age 70 years, 69% male) were included and had a median follow up of 2.7 years: 39 411 (76.7%) were treated with an open approach and 11 979 (23.3%) with a percutaneous endovascular approach. The preferred approach for the revascularisation varied between French regions. The one year overall survival was 78.0% and 85.2% in the surgery and endovascular groups, respectively. The surgery group had a higher risk of death (hazard ratio [HR] 1.17, 95% CI 1.12 - 1.21), a higher risk of major amputation (sub-distribution HR 1.20, 95% CI 1.10 - 1.30) and lower risk of minor amputation (sub-distribution HR 0.66, 95% CI 0.60 - 0.71) than the endovascular group. Diabetes and dialysis increased the risk of major amputation by 52% and 78%, respectively. Subsequent ALI was the third most common cause of hospital re-admission within one year. ALI remains a condition at high risk of death and amputation. Individual risk factors and ALI severity need to be considered to choose between approaches. Continued prevention efforts, improved management, and access to the most suitable approach are necessary.

Validation of POD24 As a Robust Early Clinical End Point of Poor Survival in Mantle Cell Lymphoma from 1280 Patients on Clinical Trials

Background The prognosis of mantle cell lymphoma (MCL) has largely improved in the past decade; however, the disease is characterized by a heterogeneous clinical course. Several retrospective studies identified early progression of disease (i.e. within two years, POD24) as a potential overall survival (OS) surrogate, but this has not been validated in cohorts of patients prospectively included in clinical trials in rituximab maintenance era. Methods We performed a pooled analysis of French patients with MCL included in six randomized clinical trials (EU-MCL younger NCT00209222, LyMA NCT00921414, LyMA101 NCT02896582, EU-MCL elderly NCT00209209, MCL-R2 NCT01865110 and RiBVD NCT01457144). Survival analysis using Landmark approach evaluated the association of POD24 status with post-event OS for all patients: starting from POD24 event or two years for patients without POD24 event. Logistic regression models were used to evaluate the association between POD24 status and (1) clinico-biological factors at diagnosis; (2) autologous stem cell transplantation at end-of-induction (ASCT) and anti-CD20 maintenance (RM) in responding patients after induction only. Results Among 1386 MCL patients, 106 censored for clinical follow-up before 24 months were excluded from the analysis, leading to 1280 patients evaluable for POD24 status: 299 with a POD24 event and 981 without. The 299 (23%) patients with a POD24 event had a post-event median OS of 9.3 months (95% CI 8.4-11.8) versus not reached in patients without POD24 event (95% CI 97.8-NR). Within the 981 non-POD24 patients, 314 presented a late relapse with a post-relapse median OS of 49.4 months (95% CI 30.4-56.8), significantly longer than OS of POD24 patients (HR=0.39; 95%CI 0.31-0.48; p<0.001). Compared to patients without a POD24 event, POD24 patients were older, had more frequently a performance status >1, elevated LDH and higher leucocytes leading to higher MIPI scores (high-risk MIPI 61% vs. 29%; p<0.001), more frequent blastoid variant (24% vs. 9%; p<0.001) and Ki67 > 30% (45% vs. 23%, p<0.001). Regarding treatment, POD24 patients had less frequently received high-dose cytarabine (21% vs. 39%, p<0.001) as well as ASCT (26% vs. 47%, p<0.001). In a final model, including baseline factors and treatment strategies, induction was not associated with risk of POD24, and only baseline variables (age, performance status, LDH, leucocytes and Ki67>30%) remained significantly associated with POD24 status. Within responding patients only (CR/CRu/PR at end-of-induction, n=1000), 150 had a POD24 event, and ASCT or RM were not significantly associated with POD24 status whereas age, LDH and Ki67>30% remained significant. Conclusion Using this large dataset of patients included in clinical trials, we confirm that POD24 can be used as a surrogate for OS in MCL. ASCT as well as RM have not a clear benefit to prevent early relapse within two years after the diagnosis in responding patients at end-of-induction.

Difficult-to-treat axial spondyloarthritis is associated with psoriasis, peripheral involvement and comorbidities: results of an observational nationwide study

ObjectivesTo determine the cumulative incidence and identify the factors associated with difficult-to-treat axial spondyloarthritis (D2T-axSpA) in French patients newly benefiting from the French ‘long-term illness’ (LTI) social security scheme for...

Information provision and follow-up of French patients with implantable cardioverter-defibrillators: The APODEC survey

BackgroundImplantable cardioverter-defibrillators reduce mortality, but the electric shocks delivered can impact the patient's quality of life. Patient education is an efficient way to reduce the stress related to both the device and the disease. AimsWe assessed the evolution of knowledge and satisfaction of implantable cardioverter-defibrillator recipients regarding their cardiac disease, implantable cardioverter-defibrillator implantation, follow-up complications, remote monitoring and daily life recommendations. Quality of life, implantable cardioverter-defibrillator-related stress levels and remote monitoring benefits were also evaluated. MethodsA self-administered questionnaire of 43 items was published on the French Association of Cardiac Electrical Device Wearers (APODEC) website and sent to registered patients. ResultsOverall, 330 patients completed the survey. Physicians were the patients’ principal information source regarding their cardiac disease (86.7%) and implantable cardioverter-defibrillator (93.3%), and 90% looked for further information after the procedure, mainly on websites (78.8%). More than half of the patients were not sufficiently informed about implantable cardioverter-defibrillators before implantation (61.2%). In the patients’ opinion, the best sources of further information were their physician (81.8%), patient associations (63.6%) and the Internet (45.8%). Although patient knowledge increased during follow-up, their knowledge could be improved regarding daily life with an implantable cardioverter-defibrillator (52.1%), remote monitoring (34.2%) and their cardiac disease (32.1%). Remote monitoring follow-up was used by 92.1% of patients and mostly improved their peace of mind (67.8%). Implantable cardioverter-defibrillator shocks were associated with major stress for patients receiving them (46.6%). ConclusionThese findings highlight the lack of information provided to implantable cardioverter-defibrillator recipients before implantation, a concerning issue to be addressed in the near future.

Management of diabetic macular oedema in France from 2012 to 2018: The nationwide LANDSCAPE study.

To describe the management of diabetic macular oedema (DME) patients from the entire French population between 2012 and 2018. In this retrospective longitudinal study, we identified adults treated for DME from the French population using the exhaustive French National Health Information database (SNDS), and an algorithm based on diagnosis and procedure codes, and reimbursed treatments. Between 2012 and 2018, we identified 53 584 treated DME patients, who were followed for up to 7 years from DME treatment initiation. Optical coherence tomography (OCT) became the predominant imaging tool to diagnose DME. Only 14% of patients consulted a diabetologist or endocrinologist in the 3 months prior to initiating DME treatment, whereas 84% consulted a general practitioner. The percentage of patients consulting an ophthalmologist declined over time, from 97% of patients in Year 1 (median of 9 consultations), to 46% in Year 7 (median of 7 consultations). The median DME treatment duration with an anti-VEGF and/or dexamethasone implant treatment was 9 months; 54% of patients had a treatment duration less than 1 year. First-line treatment was more common with ranibizumab (55% of patients) than with aflibercept (30%), or dexamethasone implant (15%). About 25% of patients who initiated anti-VEGF treatment switched treatment at least once, while 30% of patients who initiated dexamethasone implant switched to anti-VEGF treatment at least once. French DME patients seem well-monitored by their ophthalmologist, but median DME treatment duration was just 9 months. These results emphasise the challenge to manage and treat patients with DME over the long term.

Hereditary transthyretin amyloidosis in middle-aged and elderly patients with idiopathic polyneuropathy: a nationwide prospective study

Background Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from TTR gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available. Methods In this 5 year-long (2017–2021) nationwide prospective study, we systematically analysed the TTR gene in French patients with age >50 years with a progressive idiopathic polyneuropathy. Results 553 patients (70% males) with a mean age of 70 years were included. A TTR gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met TTR variation in 10 cases. In comparison with patients with no TTR gene pathogenic variants (n = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, p = .007), significant weight loss (33 vs 11%, p = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, p = .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives. Conclusion In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.

A preoperative CT radiomics model to predict disease-free survival in patients with pancreatic neuroendocrine tumors.

Imaging has demonstrated capabilities in the diagnosis of pancreatic neuroendocrine tumors (pNETs) but its utility for prognostic prediction has not been elucidated yet. The aim of this study was to build a radiomics model using preoperative computed tomography (CT) data that may help predict recurrence-free survival (RFS) or overall survival (OS) in patients with pNET. Radiomics features of preoperative CT data obtained from patients with surgically resected pNET were extracted using 3D-Slicer® software with manual segmentation. Discriminant features were selected with penalized regression using least absolute shrinkage and selection operator method with training on tumor Ki67 rate (≤2 or >2). Selected features were used to build a radiomics index ranging from 0 to 1. A receiving operator curve was built to select optimal cut-off value of radiomics index to predict patient RFS and OS. RFS and OS were assessed using Kaplan-Meier analysis. Thirty-seven patients (median age, 61 years; 20 men) with 37 pNETs (Grade1, 21/37 [56%]; Grade 2, 11/37 [29%]; Grade 3, 4/37 [10%]) were included. Patients with a radiomics index >0.4 had a shorter median RFS (36 months; range: 1-133) than those with a radiomics index ≤0.4 (84 months; range: 9-148) (P = 0.013). No associations were found between radiomics index and OS (P = 0.86). The proposed radiomics index allows identifying patients with shorter RFS after pNET surgery. This result, however, requires prospective validation but may improve patient' care by intensifying imaging follow-up for those identified at high risk of recurrence.

Real-World Treatment Patterns Among French Patients With Metastatic Castration-Resistant Prostate Cancer Under Abiraterone or Enzalutamide.

Using large French retrospective study cohort of chemotherapy-naïve metastatic castration-resistant prostate cancer patients (mCRPC; n=10,308) comparing survival between patients who initiated abiraterone (ABI; 64%) and those initiating enzalutamide (ENZ; 36%), the present objective was to describe treatment patterns in the 2 years following initiation. Using the national health data system (SNDS) from 2014 to 2018, we first explored the number of treatment lines, and secondly, patterns of patient management using state sequence analysis; cluster analyses were performed on the 0 to 12 month and 13 to 24 month periods. Age, Charlson score, and duration of androgen deprivation therapy (ADT) were obtained for each cluster in the first year of follow-up. Patients with only 1 treatment line accounted for 52%. In the 0 to 12 month sequence analysis, the main clusters among ABI/ENZ new users involved patients who continued the initial treatment (54% of 65% respectively) and discontinued active treatment (14.5% for both). Less than 2 years exposure to ADT prior to ABI/ENZ initiation was frequently observed for noncontrolled mCRPC, as shown in the death and switch from ABI/ENZ to docetaxel clusters. The clusters for a switch ABI/ENZ to ENZ/ABI involved 6% to 11% of the patients. Our study suggested fairly similar patterns between ABI and ENZ initiation. The cluster of patients with active treatment discontinuation needs to be further investigated, as well as factors influencing therapeutic choice. Better understanding for the use of second-generation hormone therapy in mCRPC in real life, could improve its implementation by clinicians in the early stages of prostate cancer.

The clinical and financial burden of nonhepatocellular carcinoma focal lesions detected during the surveillance of patients with cirrhosis.

HCC surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes, and costs of non-HCC HFL detected during surveillance. We retrospectively analyzed nonstandardized workup performed in French patients included in HCC surveillance programs recruited in 57 French tertiary centers (ANRS CirVir and CIRRAL cohorts, HCC 2000 trial). The overall cost of workup was evaluated, with an estimation of an average cost per patient for the entire population and per lesion detected. A total of 3295 patients were followed up for 59.8 months, 391 (11.9%) patients developed HCCs (5-year incidence: 12.1%), and 633 (19.2%) developed non-HCC HFLs (5-year incidence: 21.8%). Characterization of non-HCC HFL required a median additional of 0.7 exams per year. A total of 11.8% of non-HCC HFLs were not confirmed on recall procedures, and 19.6% of non-HCC HFLs remained undetermined. A definite diagnosis of benign liver lesions was made in 65.1%, and malignant tumors were diagnosed in 3.5%. The survival of patients with benign or undetermined non-HCC HFL was similar to that of patients who never developed any HFL (5-year survival 92% vs. 88%, p = 0.07). The average cost of the diagnostic workup was 1087€ for non-HCC HFL and €1572 for HCC. Non-HCC HFLs are frequently detected in patients with cirrhosis, and do not impact prognosis, but trigger substantial costs. This burden must be considered in cost-effectiveness analyses of future personalized surveillance strategies.

Post-traumatic stress disorder symptoms and quality of life among older patients with cancer during the COVID-19 pandemic

IntroductionThe Coronavirus (COVID-19) pandemic and its associated health restrictions have harmed the population psychologically. We aimed to compare the post-traumatic stress disorder (PTSD) symptoms and Quality of Life (QoL) in older French patients with cancer to the younger ones. Materials and MethodsThis longitudinal multicenter study named COVIPACT began in April 2020 during the first French lockdown and has included 579 outpatients receiving treatment for a solid or hematological malignancy. Data were collected every three months, namely at the first release period (M3), at the second lockdown (M6), at the second release period (M9), and finally at the last curfew period (M12) in France. Standardized validated self-questionnaires were used to assess PTSD symptoms (using the Event Scale–Revised self-questionnaire), insomnia (through the Insomnia Severity Index questionnaire), QoL (using the Functional Assessment of Cancer Therapy - General questionnaire), and cognitive complaints (through the Functional Assessment of Cancer Therapy – Cognition questionnaire). Student (or Wilcoxon) tests and Chi-squared tests were used for continuous or discrete variables, respectively. We conducted linear mixed model to study the change during follow-up. ResultsOut of 579 included patients, 157 (27%) were ≥ 70 years old at baseline, of whom 104 participated in the longitudinal study. At baseline, older patients reported fewer PTSD symptoms (17% versus 23%, p = .06), insomnia (17% versus 27%, p = .02), and cognitive complaint (3% versus 16%, p < .01) than younger patients. QoL at baseline was similar between age subgroups. We observed no significant difference in the trajectory of PTSD symptoms, insomnia, or emotional well-being between both groups during the follow-up. Cognitive complaints were lower at baseline in older patients but steadily increased during the follow-up and reached the same level as younger patients at one year. DiscussionOne in five older patients reported PTSD symptoms, evolving similarly to younger patients during the first year of the COVID-19 pandemic. While cognitive complaints tend to recover in a bell-shaped curve at one year in younger patients, the trend is increasing in older ones. Screening for PTSD symptoms and late cognitive impairment should be given special attention in older patients.Trial Registration:Clinicaltrials.gov identifier: NCT04366154

Multinucleated giant cells of bladder mucosa are modified telocytes: Diagnostic and immunohistochemistry algorithm and relation to PD-L1 expression score.

Multinucleated giant cells (MGCs) in bladder carcinomas are poorly studied. To describe the function, morphogenesis, and origin of mononuclear and MGCs in urothelial carcinoma (UC) of the bladder in Bulgarian and French patients. Urothelial bladder carcinomas (n = 104) from 2016-2020 were analyzed retrospectively using immunohistochemical (IHC) and histochemical stain examination. Giant cells in the bladder stroma were found in 35.6% of cases, more often in high-grades. We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers (vimentin, smooth muscle actin, Desmin, and CD34) and the macrophage marker CD68. Furthermore, IHC studies revealed the following profile of these cells: Positive for p16; negative for epithelial (CK AE1/AE3 and GATA-3), vascular (CD31), neural (PS100 and C-KIT), cambial, blastic (CD34-blasts and C-KIT), and immune markers (IG G, immunoglobulin G4, and PD-L1); no proliferative activity, possess no specific immune function, and cannot be used to calculate the Combined Positive Score scale. In conclusion, the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant, although nonspecific, histological marker for chronic bladder damage, reflecting the chronic irritation or inflammation. Likewise, according to the morphological and IHC of the mono- and multinucleated giant cells in the bladder, they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.

The first quick olfactory test specific for Alzheimer's disease and French culture.

Olfactory identification disorder is considered a promising early biomarker of Alzheimer's disease (AD). The QUICK TODA2 can be used as a short olfactory screening tool specific for French AD patients. The selection of AD specific odorants and the design of this screening were the main objectives of this twofold study. In study 1, the TODA2 olfactory test was administered to 43 mild-AD patients and 45 healthy controls (HC) in five memory centres in France. The selection of AD specific odorants was based on the differences in the proportion of correct answers and in the threshold means between AD and HC groups. In study 2, another set of 19 mild-AD patient were included at the memory centre of Nice Hospital. All participants completed the olfactory assessment pipeline including the QUICK TODA2, TODA2 and Sniffin' Sticks Identification sub-Test (SST-i). The individual scores of the three tests were correlated. In study 1, ten TODA2 odorants could significantly differentiate AD participants from controls. We selected the six most AD-sensitive items to design the QUICK TODA2. In study 2, we reported strong significant correlations between QUICK TODA2 and TODA2 (ρ(17) = 0.68, p = 0.001**), SST-i and QUICK TODA2 (ρ(17) = 0.65, p = 0.002**), SST-i and TODA2 (ρ(17) = 0.57, p = 0.01*). QUICK TODA2 is a 5-min non-invasive olfactory AD screening tool dedicated to French culture. Its results converge with those of longer, validated olfactory tests. It could be used as a quick screening tool in the general daily practice before an extensive assessment in memory centres.