Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
1.
Eur J Nucl Med Mol Imaging ; 51(5): 1297-1309, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38095675

RESUMO

PURPOSE: Evaluate the benefit of 2-deoxy-2-[18F]-fluoro-D-glucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) for the therapeutic assessment of Abatacept (ABA) as first-line therapy in early-onset polymyalgia rheumatica (PMR) patients. METHODS: This was an ancillary study of ALORS trial (Abatacept in earLy Onset polymyalgia Rheumatica Study) assessing the ability of ABA versus placebo to achieve low disease activity (C-Reactive Protein PMR activity score (CRP PMR-AS) ≤ to 10) without glucocorticoid (GC) at week 12 in patients with early-onset PMR. The patients underwent [18F] FDG PET/CT at baseline and after 12 weeks of treatment. Responses to treatments were evaluated according to CRP PMR-AS, Erythrocyte Sedimentation Rate (ESR) PMR-AS, Clin PMR-AS, and CRP-Imputed (Imput-CRP) PMR-AS. Quantitative score by maximal standardized uptake value (SUVmax) and combined qualitative scores according to liver uptake (Leuven, Leuven/Groningen, and Besançon Scores) were used for assessment of [18F] FDG uptake in regions of interest (ROI) usually affected in PMR. Student's t-test was applied to evaluate the clinical, biological, and [18F] FDG uptake variation difference in ABA and placebo groups between W0 and W12. Subgroup analysis by GC rescue was performed. RESULTS: At W12, there was no significant difference according to SUVmax between the ABA and the placebo groups in all ROI. Subgroup analysis according to GC administration demonstrated a significant (p 0.047) decrease in SUVmax within the left sternoclavicular joint ROI in the ABA group (- 0.8) compared to the placebo group (+ 0.6) without GC rescue. Other results did not reveal any significant difference between the ABA and placebo groups. According to combined qualitative scores, there was no significant difference between ABA and placebo groups for the direct comparison analysis and subgroup analysis according to GC rescue. CONCLUSION: [18F] FDG PET/CT uptake did not decrease significantly after ABA compared to placebo in anatomical areas usually affected in PMR patients. These results are correlated with the clinical-biological therapeutic assessment. CLINICAL TRIAL REGISTRATION: The study was approved by the appropriate ethics committee (CPP Sud-Est II Ref CPP: 2018-33), and all patients gave their written informed consent before study enrollment. The protocol was registered on Clinicaltrials.gov (NCT03632187).


Assuntos
Arterite de Células Gigantes , Polimialgia Reumática , Sulfonamidas , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Polimialgia Reumática/diagnóstico por imagem , Polimialgia Reumática/tratamento farmacológico , Abatacepte/uso terapêutico
2.
Rheumatology (Oxford) ; 60(6): 2545-2560, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-30770916

RESUMO

Biological abnormalities associated with B lymphocytes are a hallmark of patients with primary Sjögren's syndrome. Those patients present abnormal distribution of B lymphocytes in peripheral blood and B cells in exocrine glands. B cells produce auto-antibodies, cytokines and present antigens but can also suppressive functions. In this review, we will summarize current knowledge on B cells in primary Sjögren's syndrome patients, demonstrate their critical role in the immunopathology of the disease and describe the past and current trials targeting B cells.

4.
Rheum Dis Clin North Am ; 50(2): 255-267, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38670724

RESUMO

Polymyalgia rheumatica (PMR) immune-related adverse events (ICI-PMRs) represent a novel, distinct entity, despite many clinical, laboratory, and imaging similarities to classical PMR. Important questions remain in differentiating ICI-PMR from classical PMR, as well as other immune-related adverse events and PMR mimics. Despite this, ICI-PMR currently takes treatment cues from classical PMR, albeit with considerations relevant to cancer immunotherapy. Comparisons between ICI-PMR and classical PMR may provide further bidirectional insights, especially given that important questions remain unanswered about both diseases. The cause of classical PMR remains poorly understood, and ICI-PMR may represent a model of induced PMR, with important therapeutic implications.


Assuntos
Inibidores de Checkpoint Imunológico , Polimialgia Reumática , Polimialgia Reumática/induzido quimicamente , Polimialgia Reumática/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos
5.
RMD Open ; 10(2)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38580346

RESUMO

INTRODUCTION: Hypophosphatasia (HPP) is a rare genetic disease caused by loss-of-function mutations in the ALPL gene encoding the tissue non-specific alkaline phosphatase (ALP). Mild HPP is usually misdiagnosed in adult age. While an elevated serum ALP value draws more attention than a low value, low serum ALP should be better recognised and may lead to HPP detection. METHODS: Patients were selected from the records of the biochemistry department of six University Hospitals in France. Patients were hospitalised in the departments of rheumatology and internal medicine between 2007 and 2017. RESULTS: 56 321 hospitalised patients had at least 2 serum ALP dosages and 664 of these patients had at least 2 low serum ALP≤35 UI/L. Among these 664 patients, 482 (72.6%) had fluctuating low values (mean age 62.9 years; 60% of women) and 182 patients (27.4%) had persistent low values below 35 IU/L (mean age 53.4 years; 67% of women). Among patients with persistent hypophosphatasaemia treated with bisphosphonates, 70.8% never had ALP measurement before treatment and 20.8% were treated despite an abnormal decrease of ALP. Genetic testing was performed in 18 patients and was positive in 11. Genetic diagnosis of HPP was at least 6.0% in persistent hypophosphatasaemia and at least 15.9% in patients with at least three symptoms suggestive of HPP. CONCLUSION: In this 10-year retrospective study, 0.32% of adult patients hospitalised in the rheumatology and internal medicine departments had persistently low serum ALP, and among them, 6% had genetically proven HPP. Reported hypophosphatasaemia represented only 3.6% of hospitalised patients.


Assuntos
Hipofosfatasia , Reumatologia , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Hipofosfatasia/diagnóstico , Hipofosfatasia/epidemiologia , Hipofosfatasia/genética , Fosfatase Alcalina/genética , Estudos Retrospectivos , Mutação
6.
Arthritis Rheumatol ; 76(5): 751-762, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38130019

RESUMO

OBJECTIVE: The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti-Ro60/SSA antibodies, whereas the significance of anti-Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their anti-Ro52/TRIM21 antibody status. METHODS: Patients with SjD from the European PRECISESADS (n = 376) and the Brittany Diagnostic Suspicion of primitive Sjögren's Syndrome (DIApSS); (n = 146) cohorts were divided into four groups: double negative (Ro52-/Ro60-), isolated anti-Ro52/TRIM21 positive (Ro52+), isolated anti-Ro60/SSA positive (Ro60+), and double-positive (Ro52+/Ro60+) patients. Clinical information; EULAR Sjögren Syndrome Disease Activity Index, a score representing systemic activity; and biologic markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNA sequencing and type I and II interferon signatures were analyzed for PRECISESADS patients. RESULTS: In the DIApSS cohort, Ro52+/Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0%-11%) along with higher ß2-microglobulin (P = 0.0002), total immunoglobulin (P < 0.0001), and erythrocyte sedimentation rate levels (P = 0.002) as well as rheumatoid factor (RF) positivity (66.2% vs 20.8%-25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (P = 0.046), inflammation (P = 0.005), hypergammaglobulinemia (P < 0.0001), positive RF (P < 0.0001), leukopenia (P = 0.004), and lymphopenia (P = 0.009) in Ro52+/Ro60+ patients. Cumulative EULAR Sjögren Syndrome Disease Activity Index results further confirmed these disparities (P = 0.002). Transcriptome analysis linked anti-Ro52/TRIM21 antibody positivity to interferon pathway activation as an underlying cause for these clinical correlations. CONCLUSION: These results suggest that the combination of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies is associated with a clinical, biologic, and transcriptional profile linked to greater disease severity in SjD through the potentiation of the interferon pathway activation by anti-Ro52/TRIM21 antibodies.


Assuntos
Autoantígenos , Interferons , RNA Citoplasmático Pequeno , Ribonucleoproteínas , Índice de Gravidade de Doença , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/imunologia , Feminino , Pessoa de Meia-Idade , Masculino , Ribonucleoproteínas/imunologia , Adulto , Autoanticorpos/imunologia , Idoso , Anticorpos Antinucleares/imunologia
7.
Diabetes Res Clin Pract ; 199: 110647, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37003479

RESUMO

AIMS: Diabetic peripheral neuropathy (DPN) is a predictor of foot ulcers and leads to sedentary behaviour. This comparative study evaluated gait and feasibility of a 20-minute fast walk, at 40-60% of cardiopulmonary capacity, in individuals with DPN wearing an offloading boot and a contralateral shoe balancer. METHODS: Gait parameters were measured with inertial sensors on 32 individuals (group with DPN [n = 16], group with diabetes but without DPN [n = 9], and a group without diabetes/DPN [n = 7]). Feasibility was assessed by feedback on perceived effort and adverse events. Gait outcomes were compared between groups with or without a shoe balancer using one-way ANOVAs. RESULTS: The three groups were equivalent in terms of activity level and age and gender except for the body mass index. Both groups with diabetes exhibited minimal decreased gait speed (p > 0.005) and the DPN group exhibited increased double-support percentage (+4.6%, p = 0.01) while walking with an offloading boot and contralateral shoe balancer. The use of a contralateral shoe balancer reduced gait asymmetry. Lower physical activity level was associated with further gait deterioration in all groups. Few adverse events were reported, and 91% of participants reported that the proposed activity would be feasible daily. CONCLUSIONS: The offloading boot deteriorated gait function, but a contralateral shoe balancer minimized its impact, especially in the context of physical activity in people with diabetes and DPN.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Estudos de Viabilidade , Sapatos , Marcha , Caminhada
8.
RMD Open ; 9(4)2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-38030233

RESUMO

OBJECTIVE: Another course of immune checkpoint inhibitors (ICIs) is often considered in patients with cancer progression and previous immune-related adverse events, including inflammatory arthritis (ICI-IA), but there are limited data regarding safety of ICI rechallenge in this setting. We aimed to assess the rate and clinical features associated with ICI-IA flare/recurrence on ICI rechallenge. METHODS: We conducted a multicentre observational study including cancer patients with ICI-IA who started a second course of ICI more than 3 months after ICI discontinuation in four French university hospitals. Primary outcome was the frequency of ICI flare/recurrence after ICI rechallenge. RESULTS: Twenty-three patients were included. At the time of ICI rechallenge, 18 patients reported no symptoms of ICI-IA (78%) and 5 had grade 1 (22%), 11 patients (48%) were not receiving any ICI-IA treatment, 11 (48%) were still on prednisone, 2 (9%) were on conventional synthetic disease-modifying antirheumatic drugs and 1 (4%) on anti-IL-6. ICI-IA flare/recurrence occurred in 12 patients (52%) with a median time of 1 month after ICI rechallenge. ICI-IA phenotype, disease activity and ICI-IA treatment at the time of ICI rechallenge did not differ according to ICI-IA flare/recurrence status. CONCLUSION: In this first observational study of ICI-IA patients rechallenged with ICI, about half of the patients experienced ICI-IA flare/recurrence with a similar phenotype but occurring earlier than the initial ICI-IA, warranting close monitoring during the first month of retreatment. Risk of flare did not differ according to baseline immunosuppressive treatment at the time of rechallenge.


Assuntos
Artrite , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Neoplasias/tratamento farmacológico , Imunossupressores/uso terapêutico
9.
Lancet Rheumatol ; 5(12): e728-e735, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38251563

RESUMO

BACKGROUND: Medium-dose glucocorticoids can improve symptoms in nearly all patients with polymyalgia rheumatica. According to its good safety profile, abatacept could be used instead of glucocorticoids in early polymyalgia rheumatica. We aimed to determine whether the efficacy of abatacept is sufficient to justify larger studies in early polymyalgia rheumatica. METHODS: To evaluate whether abatacept allows low disease activity without glucocorticoids in early polymyalgia rheumatica, we conducted a proof-of-concept, randomised, double-blind, placebo-controlled, parallel-group trial. Participants were recruited from five centres in France (in Brest, Le Mans, Morlaix, Dinan and Saint Malo, and Strasbourg) and were included if they had recent-onset (<6 months) polymyalgia rheumatica with a C-reactive protein (CRP) polymyalgia rheumatica activity score (PMR-AS) of more than 17 without any signs or symptoms of giant cell arteritis (clinical and [18F]fluorodeoxyglucose PET-CT evaluation). Participants were randomly assigned (1:1) to receive weekly subcutaneous abatacept (125 mg) or matching placebo, with glucocorticoid rescue therapy allowed in cases of high disease activity, for 12 weeks, and then glucocorticoid treatment based on disease activity, until week 36. Investigators, patients, outcome assessors, and sponsor personnel were masked to group assignments. The primary endpoint was low disease activity (CRP PMR-AS ≤10) at week 12 without glucocorticoids and without rescue treatment. The study was powered to demonstrate a 60% difference in response rates between groups. Open-ended adverse events were collected at each visit by clinicians and were categorised following system organ class classification after study completion. The ALORS trial is registered with ClinicalTrials.gov, NCT03632187. FINDINGS: 34 patients (22 women and 12 men) were randomly assigned between Dec 13, 2018, and Oct 21, 2021. All patients who had been randomly assigned were included in the analysis. The primary endpoint was reached by eight (50%) of 16 patients in the abatacept group and four (22%) of 18 patients in the placebo group (relative risk 2·2 [0·9-5·5]); crude p=0·15; adjusted p=0·070). Eight (50%) patients in the abatacept and 15 (83%) in the placebo group had adverse events. Four patients (one [6%] in the abatacept group and three [17%] in the placebo group) had serious adverse events. There were no deaths or new safety concerns. INTERPRETATION: This study suggests that the effect of abatacept alone is not strong enough to justify larger studies in early polymyalgia rheumatica. This is only a first step in deciding whether a larger study should be conducted in early polymyalgia rheumatica and does not exclude a potential effect of abatacept in glucocorticoid-dependent polymyalgia rheumatica. FUNDING: BMS Pharma France.


Assuntos
Arterite de Células Gigantes , Polimialgia Reumática , Feminino , Humanos , Masculino , Abatacepte/efeitos adversos , Proteína C-Reativa , Glucocorticoides/efeitos adversos , Polimialgia Reumática/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudo de Prova de Conceito
10.
Nat Rev Rheumatol ; 18(11): 641-656, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36198831

RESUMO

Immune-checkpoint inhibitors (ICIs) have dramatically changed the management of advanced cancers. Designed to enhance the antitumour immune response, they can also cause off-target immune-related adverse events (irAEs), which are sometimes severe. Although the efficacy of ICIs suggests that they could have wide-ranging benefits, clinical trials of the drugs have so far excluded patients with pre-existing autoimmune disease. However, evidence is accumulating with regard to the use of ICIs in this 'at-risk' population, with retrospective data suggesting that they have an acceptable safety profile, but that there is a risk of disease flare or other irAE occurrence. The management of immunosuppressive drugs at ICI initiation in patients with autoimmune disease (or later in instances of disease flare or irAE) remains a question of particular interest in clinical practice, in which there is always a search for the balance between protecting against autoimmunity and ensuring a good tumour response. Although temporary use of immunosuppressants seems safe, prolonged use or use at ICI initiation might hamper the antitumour immune response, prompting clinicians to use the minimal efficient immunosuppressive regimen. However, a new paradigm is emerging, in which inhibitors of TNF or IL-6 could have synergistic effects with ICIs on tumour response, while also preventing severe irAEs. If confirmed, this 'decoupling' effect on toxicity and efficacy could change therapeutic practice in this field. Knowledge of the current use of ICIs in patients with pre-existing autoimmune disease, particularly with regard to the use of immunosuppressive drugs and/or biologic DMARDs, can help to guide clinical practice.


Assuntos
Antirreumáticos , Doenças Autoimunes , Produtos Biológicos , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Antirreumáticos/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Exacerbação dos Sintomas
11.
Pain ; 163(7): 1335-1345, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34654779

RESUMO

ABSTRACT: Top-down processes allow the selection and prioritization of information by limiting attentional capture by distractors, and these mechanisms depend on task demands such as working memory (WM) load. However, bottom-up processes give salient stimuli a stronger neuronal representation and provoke attentional capture. The aim of this study was to examine the effect of salient nociceptive stimuli on WM while manipulating task demands. Twenty-one healthy participants performed a change detection task during which they had to determine whether 2 successive visual arrays were different or the same. Task demands were modulated by manipulating the WM load (set size included 2 or 4 objects to recall) and by the correspondence between the 2 successive visual arrays (change vs no change). Innocuous stimuli (control) or nociceptive stimuli (distractors) were delivered during the delay period between the 2 visual arrays. Contralateral delay activity and laser-evoked potentials were recorded to examine neural markers of visual WM and nociceptive processes. Nociceptive stimuli decreased WM performance depending on task demands (all P < 0.05). Moreover, compared with control stimuli, nociceptive stimuli abolished the increase in contralateral delay activity amplitude for set size 4 vs set size 2 (P = 0.04). Consistent with these results, laser-evoked potential amplitude was not decreased when task demands were high (P = 0.5). These findings indicate that WM may shield cognition from nociceptive stimuli, but nociceptive stimuli disrupt WM and alter task performance when cognitive resources become insufficient to process all task-relevant information.


Assuntos
Memória de Curto Prazo , Nociceptividade , Atenção/fisiologia , Cognição/fisiologia , Eletroencefalografia/métodos , Humanos , Memória de Curto Prazo/fisiologia , Nociceptividade/fisiologia
12.
Joint Bone Spine ; 89(4): 105403, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35508288

RESUMO

OBJECTIVES: We aimed to analyze rheumatic immune-related (ir) and nonimmune-related adverse events (AEs) due to immune-checkpoint inhibitors (ICIs) targeting programmed cell death-1 or its ligand PD-(L)1 in lung cancer patients from the available literature. METHODS: We performed a systematic review and meta-analysis of phase III randomized clinical trials (RCTs) assessing PD-(L)1-ICIs in lung cancer patients, from inception until January 12th, 2021. We extracted data of each trial to estimate odds ratio (OR) for rheumatic ir or non-irAE as classified in RCTs safety data. Sensitivity analyses (by ICI, treatment group and histology) were performed. RESULTS: Eighteen RCTs met the inclusion criteria (n=12172 subjects). The OR [95%IC] for rheumatic irAE in ICIs versus controls (either placebo or chemotherapy) was 2.20 [0.85,5.72]. Among rheumatic non-irAEs, both overall and severe (grade≥3) back pain were significantly more frequent in ICIs versus controls, 2.01 [1.09;3.73] and 2.90 [1.18;7.08], respectively. The overall frequency of arthralgia was similar between ICIs and controls; by sensitivity analysis RCTs assessing ICIs in combination with chemotherapy showed a significant association with arthralgia (1.55 [1.15;2.10]). Similarly, the frequency of myalgia was significantly lower in RCTs assessing ICIs alone versus chemotherapy (OR 0.32 [0.24;0.42]). Muscular pain was not significantly increased with ICI. CONCLUSION: Rheumatic irAEs are not increased in RCTs assessing PD-(L)1 inhibitors, not reflecting the real-life incidence, therefore likely underreported or misclassified. Back pain is significantly associated with them regardless its severity, while arthralgia only when ICIs are added on conventional chemotherapy.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Pulmonares , Antineoplásicos Imunológicos/efeitos adversos , Artralgia/induzido quimicamente , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia
13.
Can J Pain ; 6(1): 185-194, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278248

RESUMO

Background: Patient engagement (PE) in research refers to partnering with people with lived experience (e.g., patients, caregivers, family) as collaborators in the research process. Although PE is increasingly being recognized as an important aspect of health research, the current state of PE among pain research trainees in Canada is unclear. Aims: The aims of this study were to describe perspectives about and experiences with PE among trainees conducting pain research in Canada, to identify perceived barriers and facilitators, and to describe recommendations to improve its implementation. Methods: A cross-sectional web-based survey (English and French) was administered to trainees at any level conducting pain research at any Canadian academic institution. Results: A total of 128 responses were received; 115 responses were complete and included in the final analysis. The majority of respondents identified as women (90/115; 78.3%), in graduate school (83/115; 72.2%), and conducting clinical pain research (83/115; 72.2%). Most respondents (103/115; 89.6%) indicated that PE is "very" or "extremely" important. Despite this, only a minority of respondents (23/111; 20.7%) indicated that they "often" or "always" implement PE within their own research. The most common barrier identified was lack of knowledge regarding the practical implementation of PE, and understanding its positive value was the most commonly reported facilitator. Recommendations for improving the implementation of PE were diverse. Conclusions: Despite viewing PE as important in research, a minority of pain research trainees regularly implement PE. Results highlight perceived barriers and facilitators to PE and provide insight to inform the development of future training and other enabling initiatives.


Contexte: L'engagement des patients dans la recherche fait référence au partenariat avec des personnes ayant une expérience vécue (p. ex. des patients, des soignants ou des membres de la famille) en tant que collaborateurs dans le processus de recherche. Bien que l'engagement des patients soit de plus en plus reconnu comme un aspect important de la recherche en santé, son état actuel chez les stagiaires en recherche sur la douleur au Canada n'est pas clair.Objectif: Les objectifs de cette étude étaient de décrire les points de vue et les expériences sur l'engagement des patients chez les stagiaires menant des études sur la douleur au Canada, de recenser les obstacles et les facilitateurs perçus et de formuler des recommandations pour améliorer sa mise en œuvre.Méthodes: Une enquête transversale sur le Web (en anglais et en français) a été menée auprès des stagiaires de tout niveau menant des études sur la douleur dans n'importe quel établissement universitaire canadien.Résultats: Au total, 128 réponses ont été reçues; 115 réponses étaient complètes et ont été incluses dans l'analyse finale. La majorité des répondants ont indiqué qu'elles étaient des femmes (90/115; 78,3 %), qu'elles étaient inscrites aux cycles supérieures (83/115 ; 72,2 %) et qu'elles effectuaient des études cliniques sur la douleur (83/115 ; 72,2 %). La plupart des répondants (103/115 ; 89,6 %) ont indiqué que l'engagement était « très ¼ ou « extrêmement ¼ important. Malgré cela, seule une minorité de répondants (23/111; 20,7 %) ont indiqué qu'ils mettaient en œuvre l'engagement des patients « souvent ¼ ou « toujours ¼ dans leur propre recherche. L'obstacle le plus fréquemment énoncé était le manque de connaissances concernant la mise en œuvre pratique de l'engagement des patients, et la compréhension de sa valeur positive était le facilitateur le plus souvent signalé. Les recommandations visant à améliorer la mise en œuvre de l'engagement des patients étaient diverses.Conclusions: Bien que l'engagement des patients soit considéré comme important dans la recherche, une minorité de stagiaires en recherche sur la douleur le mettent régulièrement en œuvre. Les résultats mettent en évidence les obstacles et les facilitateurs perçus pour l'engagement des patients et fournissent un aperçu pour éclairer l'élaboration de la formation future et d'autres initiatives habilitantes.

14.
Sci Rep ; 11(1): 12278, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112875

RESUMO

Whipple disease (WD) is a rare infectious systemic disease. Rheumatologists are at the frontline of WD diagnosis due to the early rheumatological manifestations. An early diagnosis is crucial, as usual anti-rheumatic drugs, especially TNF inhibitors, may worsen the disease course. We conducted a retrospective multicentre national study from January 2010 to April 2020 to better characterize the rheumatological features of WD. Classic WD (CWD) was defined by positive periodic acid-Schiff (PAS) staining of a small-bowel biopsy sample, and non-CWD (NCWD) was defined by negative PAS staining of a small-bowel biopsy sample but at least one positive Tropheryma whipplei (TW) polymerase chain reaction (PCR) for a digestive or extradigestive specimen. Sixty-eight patients were enrolled, including 11 CWD patients. Twenty patients (30%) received TNF inhibitors during the WD course, with inefficacy or symptom worsening. More digestive symptoms and systemic biological features were observed in CWD patients than in NCWD patients, but both patient groups had similar outcomes, especially concerning the response to antibiotics and relapse rate. Stool and saliva TW PCR sensitivity were both 100% for CWD and 75% for NCWD and 89% and 60% for small-bowel biopsy sample PCR, respectively. WD encountered in rheumatology units has many presentations, which might result from different pathophysiologies that are dependent on host immunity. Given the heterogeneous presentations and the presence of chronic carriage, multiple TW PCR tests on samples from specific rheumatological sites when possible should be performed, but samples from nonspecific digestive and extradigestive sites also have great value.


Assuntos
Doença de Whipple/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Biomarcadores , Diagnóstico Diferencial , Diagnóstico por Imagem/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Reumáticas/diagnóstico , Avaliação de Sintomas , Resultado do Tratamento , Doença de Whipple/tratamento farmacológico , Doença de Whipple/microbiologia
15.
Eur J Cancer ; 157: 474-484, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34649118

RESUMO

PURPOSE: As gut microbiota composition is an important determinant of response to immune checkpoint inhibitors (ICIs), we examined the effect of various co-medications known for their interaction with microbiota, when given at ICI initiation. PATIENTS AND METHODS: We identified patients with advanced cancer treated with ICI between May 2015 and September 2017 in our institution. Co-medications given within 1 month before or 1 month after the first administration of ICI were reviewed from medical records. Survival data were analysed with univariable Cox regression, and the combined effect of multiple factors was assessed with factor analysis of mixed data (FAMD). The impact of co-medications on immune-related adverse events (irAEs) occurrence was also assessed. RESULTS: A total of 635 patients were included. Psychotropic drugs (41%), proton pump inhibitors (PPIs; 38%), angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARBs; 32%), glucocorticoids (26%), antibiotics (24%), statins (21%) and morphine (20%) were the most prescribed co-medications. Baseline use of antibiotics, glucocorticoids >10 mg/day, PPIs, psychotropic drugs, morphine and insulin was associated with significantly shortened overall survival and decreased tumour response, whereas coadministration of statins, ACEs and/or ARBs, non-steroidal anti-inflammatory drugs, aspirin and oral antidiabetic drugs did not impact patient outcomes. Treatments that altered the response to ICI were also associated with a decreased incidence of irAEs. FAMD revealed the respective weight of each factor or co-medication on the oncological outcomes. CONCLUSION: Co-medications must be carefully assessed at the time of ICI initiation and clinicians aware of their possible deleterious effect, notably for PPIs, glucocorticoids, antibiotics and psychotropic drugs.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias/tratamento farmacológico , Medicamentos sob Prescrição/farmacologia , Idoso , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Comorbidade , Interações Medicamentosas , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/imunologia , Medicamentos sob Prescrição/uso terapêutico , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos
16.
J Physiol Sci ; 70(1): 46, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023474

RESUMO

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with chronic abdominal pain and altered pain processing. The aim of this study was to examine whether attentional processes contribute to altered pain inhibition processes in patients with IBS. Nine female patients with IBS and nine age-/sex-matched controls were included in a pain inhibition paradigm using counter-stimulation and distraction with electroencephalography. Patients with IBS showed no inhibition of pain-related brain activity by heterotopic noxious counter-stimulation (HNCS) or selective attention. In the control group, HNCS and selective attention decreased the N100, P260 and high-gamma oscillation power. In addition, pain-related high-gamma power in sensorimotor, anterior cingulate and left dorsolateral prefrontal cortex was decreased by HNCS and selective attention in the control group, but not in patients with IBS. These results indicate that the central pain inhibition deficit in IBS reflects interactions between several brain processes related to pain and attention.


Assuntos
Dor Abdominal/fisiopatologia , Atenção/fisiologia , Síndrome do Intestino Irritável/fisiopatologia , Dor Abdominal/etiologia , Dor Abdominal/psicologia , Adulto , Ansiedade/etiologia , Ansiedade/fisiopatologia , Ansiedade/psicologia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Síndrome do Intestino Irritável/psicologia , Limiar da Dor/fisiologia
17.
Arthritis Rheumatol ; 71(12): 2100-2111, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31379105

RESUMO

OBJECTIVE: Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune-related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer. METHODS: A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response. RESULTS: The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty-four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression-free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression-free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation. CONCLUSION: Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças Autoimunes/tratamento farmacológico , Imunossupressores/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/complicações , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Exacerbação dos Sintomas , Resultado do Tratamento
18.
Expert Rev Anticancer Ther ; 18(10): 981-989, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29995451

RESUMO

INTRODUCTION: Because of their efficacy against numerous cancers, immune-checkpoint inhibitors (ICIs), anti-cytotoxic T-lymphocyte antigen-4, and anti-programmed cell death monoclonal antibodies are being used ever more often in oncology. However, some patients were excluded from clinical trials because of their comorbidities despite their potentially higher cancer frequencies, as is the case for immunocompromised patients. Areas covered: We analyzed reported preclinical and clinical information and evaluated the risk/benefit ratio for four immunocompromised populations: people living with human immunodeficiency virus (PLHs), solid-organ transplant recipients, recipients of hematopoietic stem-cell allografts, and patients with autoimmune diseases. Expert commentary: Information available in the literature is fragmentary and scarce, making it difficult to evaluate the risk/benefit ratio. It can, nonetheless, be noted that ICI use in PLHs seems possible. For solid-organ transplant recipients, the risk for the graft seems elevated. For the other two populations, it is difficult to conclude at this time.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Hospedeiro Imunocomprometido/imunologia , Neoplasias/tratamento farmacológico , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Antígeno CTLA-4/imunologia , Ensaios Clínicos como Assunto/métodos , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Transplantados
20.
Arthritis Rheumatol ; 72(3): 506-508, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31609501
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA