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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
104.
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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DL Domingo MI Trujillo SE Council MA Merideth LB Gordon T Wu WJ Introne WA Gahl TC Hart 《Oral diseases》2009,15(3):187-195
Objective: Hutchinson-Gilford progeria syndrome (HGPS) is a rare early-onset accelerated senescence syndrome. In HGPS, a recently identified de novo dominant mutation of the lamin A gene ( LMNA ) produces abnormal lamin A, resulting in compromised nuclear membrane integrity. Clinical features include sclerotic skin, cardiovascular and bone abnormalities, and marked growth retardation. Craniofacial features include 'bird-like' facies, alopecia, craniofacial disproportion, and dental crowding. Our prospective study describes dental, oral soft tissue, and craniofacial bone features in HGPS.
Methods: Fifteen patients with confirmed p.G608G LMNA mutation (1–17 years, seven males, eight females) received comprehensive oral evaluations. Anomalies of oral soft tissue, gnathic bones, and dentition were identified.
Results: Radiographic findings included hypodontia ( n = 7), dysmorphic teeth ( n = 5), steep mandibular angles ( n = 11), and thin basal bone ( n = 11). Soft tissue findings included ogival palatal arch ( n = 8), median sagittal palatal fissure ( n = 7), and ankyloglossia ( n = 7). Calculated dental ages (9 months to 11 years 2 months) were significantly lower than chronological ages (1 year 6 months to 17 years 8 months) ( P = 0.002). Eleven children manifested a shorter mandibular body, anterior/posterior cranial base and ramus, but a larger gonial angle, compared to age/gender/race norms.
Conclusion: Novel oral-craniofacial phenotypes and quantification of previously reported features are presented. Our findings expand the HGPS phenotype and provide additional insight into the complex pathogenesis of HGPS. 相似文献
Methods: Fifteen patients with confirmed p.G608G LMNA mutation (1–17 years, seven males, eight females) received comprehensive oral evaluations. Anomalies of oral soft tissue, gnathic bones, and dentition were identified.
Results: Radiographic findings included hypodontia ( n = 7), dysmorphic teeth ( n = 5), steep mandibular angles ( n = 11), and thin basal bone ( n = 11). Soft tissue findings included ogival palatal arch ( n = 8), median sagittal palatal fissure ( n = 7), and ankyloglossia ( n = 7). Calculated dental ages (9 months to 11 years 2 months) were significantly lower than chronological ages (1 year 6 months to 17 years 8 months) ( P = 0.002). Eleven children manifested a shorter mandibular body, anterior/posterior cranial base and ramus, but a larger gonial angle, compared to age/gender/race norms.
Conclusion: Novel oral-craniofacial phenotypes and quantification of previously reported features are presented. Our findings expand the HGPS phenotype and provide additional insight into the complex pathogenesis of HGPS. 相似文献
109.
Kamamoto M Machida J Yamaguchi S Kimura M Ono T Jezewski PA Higashi Y Nakayama A Shimozato K Tokita Y 《European journal of human genetics : EJHG》2011,19(8):844-850
Multiple previous reports confirm that several missense alleles of MSX1 exhibit Mendelian inheritance of an oligodontia phenotype (agenesis of more than six secondary teeth besides third molars). However, the extent to which missense MSX1 alleles contribute to common, multifactorial disorders is less certain. It is still not yet clear whether multiple non-synonomous MSX1-coding variants identified among patients with oral clefting are merely neutral polymorphisms or whether any of these might represent real mutations with mild effects. The present work steps toward resolving these issues for at least one MSX1 allele: R151S, previously identified in a single Japanese proband with unilateral cleft lip and palate. Candidate gene sequencing within a patient cohort demonstrating mild tooth agenesis (loss of six or less secondary teeth besides third molars, hypodontia), secondarily identified this same MSX1 variant, functioning as a mildly deleterious, moderately penetrant allele. Four of five heterozygous R151S individuals from one Japanese family exhibited the hypodontia phenotype. The in vitro functional assays of the variant protein display partial repression activity with normal nuclear localization. These data establish that the MSX1-R151S allele is a low-frequency, mildly deleterious allele for familial hypodontia that alone is insufficient to cause oral facial clefting. Yet, as this work also establishes its hypomorphic nature, it suggests that it may in fact contribute to the likelihood of common birth disorder phenotypes, such as partial tooth agenesis and oral facial clefting. Nevertheless, the exact mechanism in which differential pleiotropy is manifested will need further and deeper clinical and functional analyses. 相似文献
110.
G D Kersley OBE TD DL MD DSC FRCP 《Medicine, conflict, and survival》2013,29(2):109-114
Any nuclear war would be horrific and our main aim should be universal abolition of nuclear weapons. Civil defence, with its medical attributes, could certainly increase the survival rate should a disaster occur. The effect of the explosion of a nuclear warhead is outlined, together with what could be done to reduce casualties. Nuclear winter is discussed and it is suggested that the results of computerization of doubtful surmises have been treated too much as proven facts. The possibility of its occurrence should not deter emergency planning. Civil defence can save lives, and the fact that medicine as we know it would cease to exist in an all‐out nuclear war does not excuse us from doing what we can to increase the survival rate, if the worst should happen. Action should therefore be taken now to plan decentralization of resources and to instruct the public in protection, first aid and self‐sufficiency. 相似文献