RESUMO
Current rheumatology guidelines recommend exercise as a key component in the management of people with RA, however, what is lacking is evidence on its impact on sleep. Objective is to assess the feasibility of a walking-based intervention on TST, sleep quality, and sleep disturbance and to generate potential effect size estimates for a main trial. Participants were recruited at weekly rheumatology clinics and through social media. Patients with RA were randomized to a walking-based intervention consisting of 28 sessions, spread over 8 weeks (2-5 times/week), with 1 per week being supervised by a physiotherapist, or to a control group who received verbal and written advice on the benefits of exercise. Primary outcomes were recruitment, retention, protocol adherence and participant experience. The study protocol was published and registered in ClinicalTrials.gov NCT03140995. One hundred and one (101) people were identified through clinics, 36 through social media. Of these, 24 met the eligibility criteria, with 20 randomized (18% recruitment; 100% female; mean age 57 (SD 7.3 years). Ten intervention participants (100%) and eight control participants (80%) completed final assessments, with both groups equivalent for all variables at baseline. Participants in the intervention group completed 87.5% of supervised sessions and 93% of unsupervised sessions. No serious adverse events were related to the intervention. Pittsburgh Sleep Quality Index global score showed a significant mean improvement between the exercise group-6.6 (SD 3.3) compared to the control group-0.25 (SD 1.1) (p = 0.012); Intervention was feasible, safe and highly acceptable to study participants, with those participants in the exercise group reporting improvements in sleep duration and sleep quality compared to the control group. Based on these findings, a fully powered randomized trial is recommended. Trial registration number: ClinicalTrials.gov Identifier: NCT03140995 (April 25th, 2017).
Assuntos
Artrite Reumatoide/terapia , Terapia por Exercício/métodos , Transtornos do Sono-Vigília/terapia , Caminhada/fisiologia , Idoso , Artrite Reumatoide/complicações , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Método Simples-Cego , Transtornos do Sono-Vigília/complicaçõesRESUMO
Objective: The purpose of this study was to explore the experiences of people with RA of participating in an exercise intervention to improve their sleep. Methods: Using a qualitative descriptive design, semi-structured face-to-face interviews were conducted with 12 people with RA who had completed an 8-week walking-based exercise intervention to improve their total sleep time, sleep quality and sleep disturbance. Data were analysed using thematic analysis. Results: Four themes were generated: positive impact of exercise on participants' sleep ('I really didn't think any type of exercise would help me sleep better, if I'm honest'); positive experiences of the exercise intervention ('I learnt so much regarding walking that I didn't even think about'); clear mental health benefits ('If you don't sleep well then it will have a knock-on effect to your mental health'); and achieving empowerment and ownership when exercising ('I feel empowered now and confident that I'm not doing harm to myself'). Conclusion: The findings demonstrated that participants had not expected exercise to improve their sleep. Although there is a growing consensus that exercise will benefit sleep and mitigate some disease symptoms, research is severely lacking in people with RA.
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Interstitial lung diseases (ILD) are a group of heterogeneous progressive pulmonary disorders, characterised by tissue remodelling and/or fibrotic scarring of the lung parenchyma. ILD patients experience lung function decline with progressive symptoms, poor response to treatment, reduced quality of life and high mortality. ILD can be idiopathic or associated with systemic or connective tissue diseases (CTD) but idiopathic pulmonary fibrosis (IPF) is the most common form. While IPF has a male predominance, women are affected more greatly by CTD and therefore associated ILDs. The mechanisms behind biological sex differences in these progressive lung diseases remain unclear. However, differences in environmental exposures, variable expression of X-chromosome related inflammatory genes and sex hormones play a role. Here, we will outline sex-related differences in the incidence, progression and mechanisms of action of these diseases and discuss existing and novel cellular and pre-clinical studies. Furthermore, we will highlight how sex-differences are not adequately considered in pre-clinical disease models, how gender bias exists in clinical diagnosis and how women are underrepresented in clinical trials. Future action on these observations will hopefully shed light on the role of biological sex in disease development, identify potential targets for intervention and increase female participant numbers in clinical trials.
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We report a case of a 54-year-old man who developed an atypical systemic syndrome involving Raynaud's phenomenon, pulmonary fibrosis and skin thickening. These features were initially suggestive of newly diagnosed scleroderma. However, he displayed atypical clinical features of same, antinuclear antibody was negative and symptoms were refractory to various immunosuppressive therapies. CT imaging revealed a gastric mass, which later proved to be a gastrointestinal stromal tumour (GIST). Resection of the GIST leads to minimal symptomatic improvement. Surveillance imaging 1 year later revealed metastatic deposits. He was subsequently initiated on imatinib therapy, which led to a rapid improvement in fibrotic changes within weeks. While there have been previous descriptions of paraneoplastic fibrotic disorders, this is the first description of a scleroderma mimic in the setting of a GIST. It highlights an important potential overlap in the pathogenesis of these disease processes and the potential efficacy of tyrosine kinase inhibitors for scleroderma-like fibrotic disorders.
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Tumores do Estroma Gastrointestinal , Doença de Raynaud , Esclerodermia Localizada , Escleroderma Sistêmico , Neoplasias Gástricas , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnósticoRESUMO
OBJECTIVE: Monogenic Behçet's disease (BD)-like conditions are increasingly recognized and to date have been found to predominantly involve loss-of-function variants in TNFAIP3. This study was undertaken to identify genetic and pathobiologic mechanisms associated with a BD-like mucocutaneous ulcerative syndrome and neuromyelitis optica (NMO) occurring in 3 generations of an Irish family (n = 5 cases and 5 familial controls). METHODS: Whole-exome sequencing was used to identify potential pathogenic variants in affected family members and determine segregation between affected and unaffected individuals. Relative v-rel reticuloendotheliosis viral oncogene homolog A (RELA) expression in peripheral blood mononuclear cells was compared by Western blotting. Human epithelial and RelA-/- mouse fibroblast experimental systems were used to determine the molecular impact of the RELA truncation in response to tumor necrosis factor (TNF). NF-κB signaling, transcriptional activation, apoptosis, and cytokine production were compared between wild-type and truncated RELA in experimental systems and patient samples. RESULTS: A heterozygous cytosine deletion at position c.1459 in RELA was detected in affected family members. This mutation resulted in a frameshift p.His487ThrfsTer7, producing a truncated protein disrupting 2 transactivation domains. The truncated RELA protein lacks a full transactivation domain. The RELA protein variants were expressed at equal levels in peripheral mononuclear cells. RelA-/- mouse embryonic fibroblasts (MEFs) expressing recombinant human RELAp.His487ThrfsTer7 were compared to those expressing wild-type RELA; however, there was no difference in RELA nuclear translocation. In RelA-/- MEFs, expression of RELAp.His487ThrfsTer7 resulted in a 1.98-fold higher ratio of cleaved caspase 3 to caspase 3 induced by TNF compared to wild-type RELA (P = 0.036). CONCLUSION: Our data indicate that RELA loss-of-function mutations cause BD-like autoinflammation and NMO via impaired NF-κB signaling and increased apoptosis.
Assuntos
Apoptose/genética , Síndrome de Behçet/genética , Citocinas/imunologia , NF-kappa B/imunologia , Neuromielite Óptica/genética , Fator de Transcrição RelA/genética , Adolescente , Adulto , Animais , Apoptose/imunologia , Síndrome de Behçet/imunologia , Criança , Feminino , Fibroblastos , Mutação da Fase de Leitura , Humanos , Irlanda , Mutação com Perda de Função , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Neuromielite Óptica/imunologia , Úlceras Orais/genética , Úlceras Orais/imunologia , Linhagem , Úlcera Cutânea/genética , Úlcera Cutânea/imunologia , Fator de Transcrição RelA/imunologia , População Branca , Adulto JovemAssuntos
Tuberculose Latente , Doenças Reumáticas , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Doenças Reumáticas/complicações , Doenças Reumáticas/epidemiologia , Centros de Atenção Terciária , Teste Tuberculínico , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: The aim of this study was to evaluate prescription practices, treatment responses, and serious adverse events of anti-tumor necrosis factor (anti-TNF) therapies in Behçet's disease (BD). MATERIAL AND METHODS: Patients with BD satisfying the International Study Group for Behçet's Disease or the International Criteria for Behçet's Disease criteria were recruited from a regional rheumatology program. The choice of anti-TNF, treatment response, and adverse events were specified. Response to treatment was evaluated by the detection of new, worsening, or improving clinical features, and management was benchmarked against current The European League against Rheumatism recommendations published in 2008. RESULTS: Out of the total of 22 patients, 18 (81.9%) received anti-TNF therapies, resulting in 14 (77.8%) complete and 4 (22.2%) partial remissions. Eleven (61.1%) patients switched to a second anti-TNF, seven patients (38.9%) required three different anti-TNFs, and one required a fourth anti-TNF to achieve remission. Two patients required retrials before their disease was controlled. Anti-TNF therapy included infliximab (IFX): n=15, 83.3%; adalimumab (ADA): n=9, 50%; golimumab: n=6, 33.3%; etanercept: n=5, 27.8%; and certolizumab pegol: n=2, 11.1%. Secondary failure was observed with IFX (4/15; 26.7%) and ADA (2/9; 22.2%), and these (100%) were manifested after at least 2 years of treatment. Five patients with potentially life-threatening laryngeal involvement received anti-TNFs successfully halting disease progression. Five allergic reactions were encountered, and five serious infections were documented involving three patients aged ≥ 50 years, all with the use of IFX. CONCLUSION: Anti-TNF therapy induced a clinical response in 100% patients and achieved complete remission in 78% patients. It provides an effective alternative option for first-line therapy in severe BD where many conventional immunosuppressive therapies fail. Patients with BD who do not respond to one or more anti-TNFs because of intolerance, ineffectiveness, or secondary failure might benefit from switching to another drug from this group or even a retrial of a previously administered anti-TNF because unsatisfactory results with one biologic is not predictive of response to another anti-TNF. For those with potentially life-threatening destructive laryngeal manifestation, anti-TNF as a first choice may be considered.
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We report a case of an 80-year-old woman being treated with rituximab and maintenance corticosteroids for long-standing scleroderma who presented with right-sided third nerve palsy. Radiological investigations including CT, MRI and MR angiography of the brain were unremarkable. The patient was discharged with a diagnosis of probable microvascular third nerve palsy but was readmitted 1â week later with total visual loss in her left eye. Despite the absence of diagnostic clinical signs, giant cell arteritis (GCA) was suspected, and she was started on intravenous corticosteroids. Left temporal artery biopsy subsequently confirmed histological findings diagnostic of GCA. Unfortunately, she remained blind in the left eye.