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We investigate third-order strongly nonlinear differential equations of the type (Φ(k(t)u″(t)))′=f(t,u(t),u′(t),u″(t)),a.e. on[0,T],\left(\Phi \left(k\left(t){u}^{^{\prime\prime} }\left(t)))^{\prime} =f\left(t,u\left(t),u^{\prime} \left(t),{u}^{^{\prime\prime} }\left(t)),\hspace{1em}\hspace{0.1em}\text{a.e. on}\hspace{0.1em}\hspace{0.33em}\left[0,T], where Φ\Phi is a strictly increasing homeomorphism, and the non-negative function kk may vanish on a set of measure zero. Using the upper and lower solution method, we prove existence results for some boundary value problems associated with the aforementioned equation. Moreover, we also consider second-order integro-differential equations like (Φ(k(t)v′(t)))′=ft,∫0tv(s)ds,v(t),v′(t),a.e. on[0,T],\left(\Phi \left(k\left(t)v^{\prime} \left(t)))^{\prime} =f\left(t,\underset{0}{\overset{t}{\int }}v\left(s){\rm{d}}s,v\left(t),v^{\prime} \left(t)\right),\hspace{1em}\hspace{0.1em}\text{a.e. on}\hspace{0.1em}\hspace{0.33em}\left[0,T], for which we provide existence results for various types of boundary conditions, including periodic, Sturm-Liouville, and Neumann-type conditions.

ABSTRACT Objective: To perform the cross-cultural adaptation of CALCULATE for Brazilian Portuguese. Method: A methodological study conducted from January to December 2021, divided into six stages: translation, synthesis, back-translation, expert committee with the application of the content validity index, pre-testing in 40 adult patients, and submission to the authors. The study took place in the intensive care units of a public tertiary teaching hospital in the interior of the state of São Paulo, Brazil. The original CALCULATE has eight risk assessment items and is stratified with a score of 0-3 (high risk) and 4-8 (very high risk). Results: After expert evaluation, the final content validity was 0.9. They suggested words and phrases that should undergo changes regarding textual equivalences, as well as definitions of acronyms and terminologies. In the pre-test, the items were assessed as suitable for understanding; only one item required additional explanation for adequacy. Conclusion: The cross-cultural adaptation of CALCULATE for Brazilian Portuguese was successfully performed, revealing a good content validity index, confirming the relevance and appropriateness of its items. CALCULATE is suitable for use in intensive care units and research and teaching centers.

Objectives: There is no consensus on the therapeutic strategy of rheumatologists for patients with spondyloarthritis (SpA) and concomitant fibromyalgia (FM).The main aim of this study was to identify, in a population of rheumatologists practicing in Normandy, France, the determinants associated with their decision to prescribe a first biologic DMARD (bDMARD) in patients with Spa/FM. Specific objectives were to evaluate professional prescribing practices to identify a set of criteria likely to contribute to the therapeutic decision of rheumatologists, and to validate the relevance of these criteria., Method: This is a cross-sectional survey-based study using a mixed (qualitative and quantitative) method. The quantitative approach was web-based and conducted among rheumatologists in Normandy., Results: The qualitative study allowed us to identify a set of criteria likely to contribute to the therapeutic decision of rheumatologists. In the quantitative study, 54/113 rheumatologists filled the questionnaire. Four criteria were considered by all respondents to contribute to their decision to prescribe a first bDMARD: arthritis on physical examination, extra-articular manifestations, systemic inflammation and structural damage on imaging., Conclusions: The determinants associated with the decision of rheumatologists to prescribe a first bDMARD in patients with SpA/FM were mostly objective, in line with the recommendations in the literature. Most criteria were more related to an approach aimed at ensuring the diagnosis of SpA than evaluating its activity or severity., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate response to NSAIDs, biological disease-modifying antirheumatic drugs (bDMARDs) should be introduced according to the recommendations of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. Until 2015, only bDMARD was recommended for axSpA in case of failure to anti-tumour necrosis factor (TNF). The 2022 Assessment of SpondyloArthritis International Society (ASAS)-EULAR recommendation proposed to start an alternative bDMARD but without advocating a switch in mode of action as proposed in rheumatoid arthritis. Since 2015, the inhibition of interleukin (IL)-17 has demonstrated efficacy in axSpA. Then, we designed a randomised multicentre clinical trial to identify the more effective treatment after a first anti-TNF failure in axSpA, comparing an anti-IL-17 to a second anti-TNF., Methods and Analysis: The ROC-SpA (Rotation Or Change of biotherapy after first anti-TNF treatment failure in axSpA patients) study is a prospective, randomised, multicentre, superiority open-label phase IV trial comparing an anti-IL-17 strategy (secukinumab or ixekizumab) to a second TNF blocker in a 1:1 ratio. Patients with an active axSpA (Bath Ankylosing Spondylitis Disease Activity Index >4 or ankylosing spondylitis disease activity score (ASDAS) >3.5) with inadequate 3 months response to a first anti-TNF and with a stable dose of conventional synthetic DMARDs, oral corticosteroids and/or NSAIDs for at least 1 month are included in 31 hospital centres in France and Monaco. The primary outcome is the ASAS40 response at week 24. The secondary outcomes are ASAS40 at weeks 12 and 52, other clinical scores (ASAS20, partial remission rate, ASDAS major improvement rate) at weeks 12, 24 and 52 with the drugs and anti-drugs concentrations at baseline, weeks 12, 24 and 52. The primary analysis is performed at the end of the study according to the intent-to-treat principle., Ethics and Dissemination: Ethics approval was obtained from the committee for the protection of persons (Comité de protection des personnes Ouest IV #12/18_1, 6 February 2018) and registered in ClinicalTrials.gov and in EudraCT. Results of this study, whether positive or negative, will be presented at national and international congresses, to national axSpA patient associations and published in a peer-reviewed journal. It could also impact the international recommendation to manage patients with axSpA., Trial Registration Number: NCT03445845 and EudraCT2017-004700-22., Competing Interests: Competing interests: ED, CM, TB-A, FR, MA, LDA and EP declare no competing interests. AF has received grants or contracts (Eli Lilly, Pfizer, AbbVie, Gilead and BMS), consulting fees (AstraZeneca, AbbVie, Pfizer and Gilead) and honorary payments (BMIS, AbbVie, Eli Lilly, Pfizer and MSD) and participated in advisory boards (Astra-Zeneca, Gilead, Novartis, AbbVie, Eli Lilly, Pfizer, J&J, Mylan and UCB). HM has received grants and contract (Celltrion Healthcare, Lilly, Medac, Nordic Pharma), consulting fees (AbbVie, Accord, Celltrion Healthcare, Johnson and Johnson, UCB) and honorary payments (AbbVie, BMS, Lilly, Pfizer) and participated in advisory boards (Celltrion Healthcare, Eli Lilly, Pfizer, UCB)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Both bone fragility and poor cognitive functions are known to contribute to fracture occurrence, but it remains unclear whether their contribution is independent of each other and which cognitive dysfunctions are most involved. This study aimed to clarify the involvement of various cognitive abilities in fall-related fractures among community-dwelling fallers aged 55 and over, and to determine whether poor cognitive abilities is a risk factor independent of bone fragility., Methods: In a cross-sectional study, we collected sociodemographic and medical data, including bone mineral density (BMD), and performed cognitive and mobility assessments in 189 individuals with a history of fall in the previous year., Results: Fallers with a fracture had poorer cognitive and mobility performance than non-injured fallers. Multivariate regressions revealed that cognition, BMD and other risk factors were independently associated with fracture among all participants (OR = 1.04, 95% CI = 1.01-1.08, p = 0.034 for completion time on part A of the Trail Making Test [TMT-A], and OR = 0.53, 95% CI = 0.33-0.84, p < 0.001 for BMD), particularly in women (OR = 0.77, 95% CI = 0.60-0.98, p = 0.039 for backward digit span score, and OR = 0.43, 95% CI = 0.25-0.75, p = 0.001 for BMD)., Conclusion: Thus, poor cognition, especially poor processing speed and working memory, is associated with an increased risk of fracture in fallers, particularly in women, regardless of BMD or other fracture risk factors. Hence, an in-depth cognitive evaluation should enhance the detection of fallers at risk of fracture, particularly in the absence of signs of osteoporosis, and thus ensure the best possible prevention., (© 2024. The Author(s).)

Objectives: To analyse in routine practice the efficacy of targeted therapies on joint involvement of patients with rheumatoid arthritis/systemic sclerosis (RA/SSc) overlap syndrome., Methods: This was a retrospective analysis of medical records of two academic centres over a 10-year period. Joint response to targeted therapies was measured according to EULAR criteria based on Disease Activity Score (DAS)-28. In addition, changes in CRP level and glucocorticoid consumption were recorded., Results: Nineteen patients were included. Methotrexate (n=11) and hydroxychloroquine (n=4) were the most used first-line treatments. Targeted therapies were frequently used (n=14). Tocilizumab was the most selected therapy (n=8), then rituximab (n=5), abatacept and anti-tumour necrosis factor (n=4). Twenty-one treatment sequences were assessed, including 18 with EULAR response criteria. Responses were "good" or "moderate" in 100% (4/4) of patients treated with abatacept, 80% (4/5) with rituximab, 40% (2/5) with tocilizumab, and 25% (1/4) with anti-TNF. T and B lymphocyte-targeted therapies (abatacept, rituximab) resulted more frequently in a "good" or "moderate" response compared to cytokine inhibitors (tocilizumab, etanercept, infliximab) with a significant decrease in DAS-28 at 6 months (-1.75; p=0.016) and a trend to a lower consumption of glucocorticoids., Conclusions: In patients with RA/SSc overlap syndrome refractory to conventional synthetic-DMARDs, T and B lymphocyte-targeted therapies seem to be a promising therapeutic option to control joint activity.