Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3–4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).

The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance.

Background: A polymorphism in exon 4 (C77G) of CD45 that alters CD45 splicing has been associated with autoimmune and infectious diseases in humans. Objective: To investigate the effect of C77G in hepatitis C virus (HCV) infected individuals and study the phenotype and function of peripheral blood mononuclear cells (PBMC) from healthy and hepatitis C infected C77G carriers. Results: C77G individuals showed an increased proportion of primed CD45RA and effector memory CD8 T cells and more rapid activation of the lymphocyte specific protein tyrosine kinase (Lck) following CD3 stimulation. Transgenic mice with CD45 expression mimicking that in human C77G variants had more activated/memory T cells, more rapid proliferative responses, and activation of Lck. Conclusions: Changes in CD45 isoform expression can alter immune function in human C77G variants and CD45 transgenic mice. The C77G allele may influence the outcome of HCV infection.

Background Health professions education has undergone major changes with the advent and adoption of digital technologies worldwide. Objective This study aims to map the existing evidence and identify gaps and research priorities to enable robust and relevant research in digital health professions education. Methods We searched for systematic reviews on the digital education of practicing and student health care professionals. We searched MEDLINE, Embase, Cochrane Library, Educational Research Information Center, CINAHL, and gray literature sources from January 2014 to July 2020. A total of 2 authors independently screened the studies, extracted the data, and synthesized the findings. We outlined the key characteristics of the included reviews, the quality of the evidence they synthesized, and recommendations for future research. We mapped the empirical findings and research recommendations against the newly developed conceptual framework. Results We identified 77 eligible systematic reviews. All of them included experimental studies and evaluated the effectiveness of digital education interventions in different health care disciplines or different digital education modalities. Most reviews included studies on various digital education modalities (22/77, 29%), virtual reality (19/77, 25%), and online education (10/77, 13%). Most reviews focused on health professions education in general (36/77, 47%), surgery (13/77, 17%), and nursing (11/77, 14%). The reviews mainly assessed participants’ skills (51/77, 66%) and knowledge (49/77, 64%) and included data from high-income countries (53/77, 69%). Our novel conceptual framework of digital health professions education comprises 6 key domains (context, infrastructure, education, learners, research, and quality improvement) and 16 subdomains. Finally, we identified 61 unique questions for future research in these reviews; these mapped to framework domains of education (29/61, 47% recommendations), context (17/61, 28% recommendations), infrastructure (9/61, 15% recommendations), learners (3/61, 5% recommendations), and research (3/61, 5% recommendations). Conclusions We identified a large number of research questions regarding digital education, which collectively reflect a diverse and comprehensive research agenda. Our conceptual framework will help educators and researchers plan, develop, and study digital education. More evidence from low- and middle-income countries is needed.

CD45 is crucial for normal lymphocyte signalling, and altered CD45 expression has major effects on immune function. Both mice and humans lacking CD45 expression are severely immunodeficient, and single-nucleotide polymorphisms in the CD45 gene that cause altered splicing have been associated with autoimmune and infectious diseases. Recently, we identified an exon 6 A138G polymorphism resulting in an increased proportion of activated CD45RO T cells and altered immune function. Here we report a significantly reduced frequency of the 138G allele in hepatitis C Japanese patients and a possibly reduced frequency in type I diabetes. The allele is widely distributed in the Far East and India, indicating that it may have a significant effect on disease burden in a large part of the human population.

Comprehensive geriatric assessment: a meta-analysis of controlled trials. Lancet 1993;342:1032-6. 2 Davey Smith G, Egger M. Incommunicable knowledge?Interpreting and applying the results of clinical trials and meta-analyses. J Clin Epidemiol (in press).

BACKGROUND Health professions education has undergone major changes with the advent and adoption of digital technologies worldwide. OBJECTIVE This study aims to map the existing evidence and identify gaps and research priorities to enable robust and relevant research in digital health professions education. METHODS We searched for systematic reviews on the digital education of practicing and student health care professionals. We searched MEDLINE, Embase, Cochrane Library, Educational Research Information Center, CINAHL, and gray literature sources from January 2014 to July 2020. A total of 2 authors independently screened the studies, extracted the data, and synthesized the findings. We outlined the key characteristics of the included reviews, the quality of the evidence they synthesized, and recommendations for future research. We mapped the empirical findings and research recommendations against the newly developed conceptual framework. RESULTS We identified 77 eligible systematic reviews. All of them included experimental studies and evaluated the effectiveness of digital education interventions in different health care disciplines or different digital education modalities. Most reviews included studies on various digital education modalities (22/77, 29%), virtual reality (19/77, 25%), and online education (10/77, 13%). Most reviews focused on health professions education in general (36/77, 47%), surgery (13/77, 17%), and nursing (11/77, 14%). The reviews mainly assessed participants’ skills (51/77, 66%) and knowledge (49/77, 64%) and included data from high-income countries (53/77, 69%). Our novel conceptual framework of digital health professions education comprises 6 key domains (context, infrastructure, education, learners, research, and quality improvement) and 16 subdomains. Finally, we identified 61 unique questions for future research in these reviews; these mapped to framework domains of education (29/61, 47% recommendations), context (17/61, 28% recommendations), infrastructure (9/61, 15% recommendations), learners (3/61, 5% recommendations), and research (3/61, 5% recommendations). CONCLUSIONS We identified a large number of research questions regarding digital education, which collectively reflect a diverse and comprehensive research agenda. Our conceptual framework will help educators and researchers plan, develop, and study digital education. More evidence from low- and middle-income countries is needed.

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