Toward designing human intervention studies to prevent osteoarthritis after knee injury: A report from an interdisciplinary OARSI 2023 workshop

Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges

Carbon dioxide laser treatment for vulvovaginal atrophy in women treated for breast cancer: Preliminary results of the feasibility EPIONE trial

Contexte et objectif: La préservation de la qualité de vie après un traitement anticancéreux est un défi majeur pour les survivantes du cancer du sein. Environ 42 à 70 % des patients qui reçoivent une thérapie systémique pour le cancer du sein, y compris une thérapie endocrinienne, développeront une atrophie vulvo-vaginale (AVV). Pour ces patientes, les traitements à base de gel couramment proposés pour les applications topiques sont restrictifs. Récemment, des approches thérapeutiques innovantes et non hormonales, telles que la thérapie laser, ont fait leur apparition. L'objectif de cette étude de faisabilité est d’étudier la sécurité et l'efficacité de la thérapie au laser CO2 chez les femmes ayant des antécédents de cancer du sein. Matériel et méthodes: Cette étude monocentrique prospective a porté sur 20 patientes atteintes d'AVV qui ont été traitées à l'hôpital universitaire Henri Mondor entre 2017 et 2018. Nous avons inclus des patientes ayant un indice de santé vaginale (IHV) 11, et à M6, seuls 15 % avaient un score de détresse sexuelle féminine > 11. Aucun effet secondaire n'a été signalé lors du suivi. Conclusion: Cette étude de faisabilité pilote a montré que le traitement par laser au dioxyde de carbone semble être une méthode efficace et sûre pour améliorer la trophicité et diminuer la sécheresse de la muqueuse vaginale chez les femmes atteintes d'atrophie vulvo-vaginale qui s'est développée après un traitement systémique du cancer du sein

Carbon dioxide laser treatment for vulvovaginal atrophy in women treated for breast cancer: Preliminary results of the feasibility EPIONE trial

International audienceBackground and objective: Quality of life preservation after anti-cancer therapy is a major challenge for breast cancer survivors. Approximately 42-70% of patients who receive systemic therapy for breast cancer, including endocrine therapy, will develop vulvovaginal atrophy (VVA). For these patients, the commonly proposed gel-based treatments for topical applications are restrictive. Recently, innovative, non-hormonal therapeutic approaches, such as laser therapy, have emerged. The purpose of this feasibility study is to investigate the safety and efficacy of CO2 laser therapy in women with a history of breast cancer.Material and methods: This prospective monocentric study included 20 patients with vulvovaginal atrophy who were treated at Henri Mondor University Hospital between 2017 and 2018. We included patients with a vaginal health index (VHI) score11, and at M6, only 15% had a female sexual distress score>11. No side effects were reported during follow-up.Conclusion: This pilot feasibility study showed that carbon dioxide laser treatment appears to be an effective and safe method to improve the trophicity and decrease vaginal mucosal dryness in women with vulvovaginal atrophy that developed after systemic breast cancer therapy

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons