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1.
Ann Rheum Dis ; 77(4): 563-570, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29306872

RESUMO

OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. TRIAL REGISTRATION NUMBER: NCT02339441.


Assuntos
Esclerodermia Difusa/diagnóstico , Índice de Gravidade de Doença , Testes Cutâneos/estatística & dados numéricos , Adulto , Área Sob a Curva , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Modelos Logísticos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , RNA Polimerase III/análise , Curva ROC , Esclerodermia Difusa/enzimologia , Esclerodermia Difusa/patologia , Pele/patologia
2.
Rheumatology (Oxford) ; 57(2): 370-381, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29207002

RESUMO

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001). Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.


Assuntos
Avaliação da Deficiência , Fadiga/fisiopatologia , Dor/fisiopatologia , Esclerodermia Difusa/fisiopatologia , Índice de Gravidade de Doença , Adulto , Efeitos Psicossociais da Doença , Europa (Continente) , Fadiga/etiologia , Feminino , Dedos , Força da Mão , Inquéritos Epidemiológicos , Humanos , Masculino , Dor/etiologia , Estudos Prospectivos , Esclerodermia Difusa/complicações , Úlcera Cutânea/etiologia , Úlcera Cutânea/fisiopatologia
3.
F1000Res ; 6: 170, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28491283

RESUMO

Open Online Courses (OOCs) are offered by Peoples-uni at http://ooc.peoples-uni.org to complement the courses run on a separate site for academic credit at http://courses.peoples-uni.org. They provide a wide range of online learning resources beyond those usually found in credit bearing Public Health courses. They are self-paced, and students can enrol themselves at any time and utilise Open Educational Resources free of copyright restrictions.  In the two years that courses have been running, 1174 students from 100 countries have registered and among the 1597 enrolments in 14 courses, 15% gained a certificate of completion. Easily accessible and appealing to a wide geographical and professional audience, OOCs have the potential to play a part in establishing global Public Health capacity building programmes.

4.
Ann Rheum Dis ; 76(7): 1207-1218, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28188239

RESUMO

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. TRIAL REGISTRATION NUMBER: NCT02339441.


Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Esclerodermia Difusa/tratamento farmacológico , Adulto , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Estudos de Coortes , Intervenção Médica Precoce , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/imunologia , Estudos Prospectivos , RNA Polimerase III/imunologia , Esclerodermia Difusa/imunologia , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
5.
BMJ Clin Evid ; 20152015 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-26683208

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies worldwide, ranging from about 1 in 3500 women (regardless of race) in the UK, to 1 in 1000 women in China, to 1 in 250 African-American women in the US. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of immunosuppressants in people with proliferative lupus nephritis? What are the effects of different immunosuppressants compared with each other in people with proliferative lupus nephritis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 448 studies. After deduplication and removal of conference abstracts, 120 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 53 studies and the further review of 67 full publications. Of the 67 full articles evaluated, four systematic reviews and one RCT were added at this update. We performed a GRADE evaluation for 13 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for 10 interventions based on the effectiveness and safety of immunosuppressants plus corticosteroids compared with corticosteroids alone, and immunosuppressants plus corticosteroids compared with each other in people with proliferative lupus nephritis (WHO grades III-V).

11.
Natl Med J India ; 27(4): 217-23, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25668169

RESUMO

Unsafe healthcare is a well-recognized issue internationally and is attracting attention in India as well. Drawing upon the various efforts that have been made to address this issue in India and abroad, we explore how we can accelerate developments and build a culture of patient safety in the Indian health sector. Using five international case studies, we describe experiences of promoting patient safety in various ways to inform future developments in India. We offer a roadmap for 2020, which contains suggestions on how India could build a culture of patient safety.


Assuntos
Segurança do Paciente , Melhoria de Qualidade , Humanos , Índia , Cultura Organizacional
12.
Indian J Med Ethics ; 10(4): 263-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24152354

RESUMO

This personal comment briefly describes the working of the General Medical Council, the medical regulator in the United Kingdom, with the aim of informing the discussion on how to regulate medical education and doctors' practice in India. Given that the ministry of health and family welfare is still debating the final constitution of the Medical Council of India, this paper is timely.


Assuntos
Educação Médica/normas , Conselho Diretor/organização & administração , Regulamentação Governamental , Licenciamento em Medicina/normas , Humanos , Índia , Modelos Organizacionais , Inovação Organizacional , Reino Unido
13.
PLoS One ; 8(1): e54419, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23372721

RESUMO

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10(-8), OR  = 1.22, CI 95%  = 1.14-1.30; rs2004640: P  = 4.60×10(-7), OR  = 0.84, CI 95%  = 0.78-0.90; rs10488631: P  = 7.53×10(-20), OR  = 1.63, CI 95%  = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10(-22), OR  = 1.75, CI 95%  = 1.56-1.97) better explained the observed association (likelihood P-value  = 1.48×10(-4)), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.


Assuntos
Predisposição Genética para Doença , Haplótipos , Fatores Reguladores de Interferon/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/genética , Alelos , Grupo com Ancestrais do Continente Europeu , Feminino , Frequência do Gene , Loci Gênicos , Humanos , Desequilíbrio de Ligação , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Fenótipo , Fatores de Risco , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/etnologia
14.
Ann Rheum Dis ; 72(12): 2032-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23444193

RESUMO

OBJECTIVE: To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2). METHODS: We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc. RESULTS: IRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (PFDR=4.12×10(-3), OR=1.27, 95% CI 1.09 to 1.47, and PFDR=5.26×10(-4), OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (PFDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF- (p=0.025, OR=1.26, 95% CI 1.03 to 1.55). CONCLUSIONS: Our data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease.


Assuntos
Cromossomos Humanos X/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Escleroderma Sistêmico/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Quinases Associadas a Receptores de Interleucina-1/genética , Desequilíbrio de Ligação , Proteína 2 de Ligação a Metil-CpG/genética , Polimorfismo de Nucleotídeo Único , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/genética , Esclerodermia Difusa/genética , Escleroderma Sistêmico/complicações
17.
J Clin Epidemiol ; 66(5): 490-5, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22537424

RESUMO

OBJECTIVES: We aimed to develop and pilot a process for joint working between Cochrane Review Groups (specialist-area groups responsible for producing Cochrane reviews) and Cochrane Fields (broad-spectrum interest groups), for identifying high priority review topics and enhancing quality and dissemination of priority reviews. STUDY DESIGN AND SETTING: We developed and piloted a framework for collaboration between a Cochrane Review Group (specializing in musculoskeletal injuries) and a Cochrane Field (focusing on health care of older people) for identifying, delivering, and disseminating priority Cochrane intervention reviews using hip fracture rehabilitation as an exemplar. The processes adopted included consultation of members of both the entities, mapping of trials from the Review Group's Specialized Register, jointly establishing criteria for topic prioritization, identification of researchers, and facilitating provision of expert peer review from the field. RESULTS: A framework for effective collaboration between a Cochrane Review Group and Cochrane Field for identifying and delivering priority Cochrane Reviews was devised and piloted. Additionally, two new Cochrane reviews, preceded by protocols, were published. CONCLUSION: The project demonstrated the feasibility and potential benefits of a structured collaboration between a Cochrane Review Group and a Cochrane Field for the identification and production of Cochrane reviews on priority topics.


Assuntos
Comportamento Cooperativo , Prioridades em Saúde , Serviços de Saúde para Idosos/organização & administração , Fraturas do Quadril/reabilitação , Literatura de Revisão como Assunto , Adulto , Idoso , Assistência à Saúde , Feminino , Humanos , Masculino , Equipe de Assistência ao Paciente/organização & administração , Projetos Piloto , Especialização , Reino Unido
19.
J Rheumatol ; 39(12): 2294-302, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23027890

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc. METHODS: We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan(®) allele discrimination technology. RESULTS: Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04-1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77-0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04-1.23). CONCLUSION: Our results suggest that the IL6 gene may influence the development of SSc and its progression.


Assuntos
Predisposição Genética para Doença , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/genética , Progressão da Doença , Europa (Continente)/epidemiologia , Grupo com Ancestrais do Continente Europeu/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Masculino , Escleroderma Sistêmico/etnologia
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