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).
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).
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%.
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.
NCT02339441.
None of these reports bridge the gulf between these unrealistic possibilities and offer a practical alternative.2 Most importantly, the public should be wary of the current “more of the same” ...political announcements that ignore urgent and important considerations such as the nature of the health and care services. 4 Full response at: www.bmj.com/content/385/bmj.q1070/rr. 1 Cunnett J Smith R. To increase public satisfaction in the NHS, we need a new conversation about how to improve it. BMJ 2024; 385: q1070. 10.1136/bmj.q1070 38740420 2 Madhok R. Re: The NHS founding principles are still appropriate today and provide a strong foundation for the future response to Crisp et al.
3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) exert favorable effects on lipoprotein metabolism, but may also possess anti-inflammatory properties. Therefore, we explored the ...activities of simvastatin, a lipophilic statin, in a Th1-driven model of murine inflammatory arthritis. We report in this study that simvastatin markedly inhibited not only developing but also clinically evident collagen-induced arthritis in doses that were unable to significantly alter cholesterol concentrations in vivo. Ex vivo analysis demonstrated significant suppression of collagen-specific Th1 humoral and cellular immune responses. Moreover, simvastatin reduced anti-CD3/anti-CD28 proliferation and IFN-gamma release from mononuclear cells derived from peripheral blood and synovial fluid. Proinflammatory cytokine production in vitro by T cell contact-activated macrophages was suppressed by simvastatin, suggesting that such observations have direct clinical relevance. These data clearly illustrate the therapeutic potential of statin-sensitive pathways in inflammatory arthritis.
The People's Open Access Education Initiative (Peoples-uni) was established as an educational charity to help reduce inequalities in access to the higher education required to build Public Health ...capacity through workforce development for health professionals in low- to middle-income countries (LMICs). Online learning, using open source software, Open Educational Resources and an international cadre of volunteer tutors, underpinned a low cost programme which produced a number of successful outcomes including university validated master's level awards, continuing professional development, positive feedback from students, and the application by alumni of skills learned. Peoples-uni closed in 2021, its programme taken over by another organisation, and this paper builds on previous reports to summarise the experience and draw lessons for others who may wish to contribute in a similar way.
Rising disease burden and health inequalities remain global concerns, highlighting the need for health systems strengthening with a sufficient and appropriately trained workforce. The current models ...for developing such a workforce are inadequate and newer approaches are needed. In this paper we describe a model for public health capacity building through online Global Learning, defined as 'innovative, integrated, global opportunities for capacity building through online learning and shared experiences between and within Low- to Middle- Income Countries and High-Income Countries, in a continuous process that helps health care workers learn as they progress through their careers'. We demonstrate how two programmes, 'Peoples-uni' and 'NextGenU.org', have implemented this model using a mix of low-cost and free online learning courses, a global community of volunteer tutors, mentors and peers, and appropriate high quality competence-based content.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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