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BackgroundRheumatoid arthritis is the most common chronic inflammatory disease in the UK. Serological status such as rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity predict poor outcomes. Early intensive treatment regimens targeting remission reduce disease activity, structural damage, and long-term disability. However, we do not know whether all patients with active disease should have such intensive treatment regimens. Can serological status be used to predict the need for intensive therapy?MethodsWe analysed samples from a published randomised controlled trial which compared four treatment regimens in patients with early active rheumatoid arthritis (disease duration <2 years): methotrexate monotherapy, double therapy (methotrexate plus either ciclosporin or prednisolone), and triple therapy (methotrexate plus ciclosporin plus prednisolone). The trial randomised 467 patients (68% female, median age 54 years [IQR 46–63]). Disease activity was assessed with the disease activity score of 28 joints (DAS28). Remission was defined as DAS28 less than 2·6 at 24 months. RF isotypes (IgM and IgA) and ACPA levels were measured with commercial ELISA kits. Statistical analysis used Pearson's chi-squared test.Findings402 (86%) patients were positive for IgM RF, 346 (74%) for IgA RF, and 346 (74%) for ACPA. 98 (21%) patients achieved remission at 24 months. In RF IgM negative cases (n=65) the proportion of patients achieving remission at 24 months was similar in all treatment groups (25%, 22%, and 30% for monotherapy, double therapy, and triple therapy, respectively). In RF IgM positive cases, significantly fewer patients achieved remission with monotherapy (13/65, 17%) and double therapy (24/157, 15%) than with triple therapy (27/80, 34%) (p=0·001). There were similar, consistent findings with IgA RF and ACPA, with significantly more seropositive patients achieving remission with triple therapy than with monotherapy.InterpretationContemporary treatment of rheumatoid arthritis emphasises the use of intensive therapy to achieve remission. However, we have shown that not all patients require such an aggressive approach to therapy. Given the heterogeneity of the diease, treatment should be personalised to the individual, which would minimise costs of treatment as well as potentially toxic side-effects. Our study shows that only seropositive patients with rheumatoid arthritis should be given more intensive therapies.FundingNational Institute for Health Research. 相似文献
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Brandon DL. Marshall Evan Wood Jean A. Shoveller Jane A. Buxton Julio SG. Montaner Thomas Kerr 《Prevention science》2011,12(2):173-180
The purpose of this study was to determine the incidence and predictors of initiating methamphetamine injection among a cohort
of injection drug users (IDU). We conducted a longitudinal analysis of IDU participating in a prospective study between June
2001 and May 2008 in Vancouver, Canada. IDU who had never reported injecting methamphetamine at the study’s commencement were
eligible. We used Cox proportional hazards models to identify the predictors of initiating methamphetamine injection. The
outcome was time to first report of methamphetamine injection. Time-updated independent variables of interest included sociodemographic
characteristics, drug use patterns, and social, economic and environmental factors. Of 1317 eligible individuals, the median
age was 39.9 and 522 (39.6%) were female. At the study’s conclusion, 200 (15.2%) participants had initiated injecting methamphetamine
(incidence density: 4.3 per 100 person-years). In multivariate analysis, age (adjusted hazard ratio [aHR]: 0.96 per year older,
95%CI: 0.95–0.98), female sex (aHR: 0.58, 95%CI: 0.41–0.82), sexual abuse (aHR: 1.63, 95%CI: 1.18–2.23), using drugs in Vancouver’s
drug scene epicentre (aHR: 2.15 95%CI: 1.49–3.10), homelessness (aHR: 1.43, 95%CI: 1.01–2.04), non-injection crack cocaine
use (aHR: 2.06, 95%CI: 1.36–3.14), and non-injection methamphetamine use (aHR: 3.69, 95%CI: 2.03–6.70) were associated with
initiating methamphetamine injection. We observed a high incidence of methamphetamine initiation, particularly among young
IDU, stimulant users, homeless individuals, and those involved in the city’s open drug scene. These data should be useful
for the development of a broad set of interventions aimed at reducing initiation into methamphetamine injection among IDU. 相似文献
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Joo Gabriel Roderjan Lúcia de Noronha Marco Augusto Stimamiglio Alejandro Correa Amanda Leitolis Ronaldo Rocha Loures Bueno Francisco Diniz Affonso da Costa 《Xenotransplantation》2019,26(3)
Tissue‐engineered heart valves aim to reproduce the biological properties of natural valves with anatomically correct structure and physiological performance. The closest alternative to creating an ideal heart valve substitute is to use decellularized porcine heart valves, due to their anatomy and availability. However, the immunological barrier and the structural maintenance limit the long‐term physiological performance of decellularized porcine heart valves. This study investigated the extracellular matrix (ECM) structure of aortic and pulmonary porcine valves decellularized by a low concentration sodium dodecyl sulfate (SDS)‐based method in order to determine the ECM scaffold (ECMS) conditions related to remodeling potential. To assess the structures of the leaflets and conduits of the heart valves, ECM components and their organization were evaluated by histology, biochemical analysis (BC), scanning electron microscopy, multiphoton microscopy, tensile test, immunofluorescence labeling (IF), and Raman microspectroscopy used to draw a profile of the cell niches. Histology and multiphoton imaging of decellularized aortic and pulmonary leaflets and conduits revealed a collagen and elastin histoarchitecture with rearrangement, loosening fibers, and glycosaminoglycan depletion confirmed by biochemistry quantification. The potential cytotoxicity of SDS residues was eliminated after 10 wash cycles. The mechanical properties of the structure of the valve indicated a functional resistance of decellularized ECM. The IF demonstrated the presence of basement membrane, suggesting a potential structure for host cell attachment. The RM analysis showed evidence of molecular interactions, suggesting conservation of the chemical composition, particularly among the protein molecular structures. The structural analyses performed in the semilunar porcine heart valves demonstrate that decellularized ECMS has structural properties that support physiological performance and potential host tissue integration. In fact, decellularized leaflet scaffolds were prone to cell interaction after human adipose‐derived stromal cell seeding and culturing. Further analysis of biocompatibility, particularly the ECM‐cell interaction, can elucidate the remodeling process, in preserved decellularized heart valve scaffold. 相似文献