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| 2. |
- Headrick, L. A., et al.
(författare)
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Exemplary Care and Learning Sites : A Model for Achieving Continual Improvement in Care and Learning in the Clinical Setting
- 2016
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Ingår i: Academic Medicine. - : Wolters Kluwer. - 1040-2446 .- 1938-808X. ; 91:3, s. 354-359
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Tidskriftsartikel (refereegranskat)abstract
- Problem Current models of health care quality improvement do not explicitly describe the role of health professions education. The authors propose the Exemplary Care and Learning Site (ECLS) model as an approach to achieving continual improvement in care and learning in the clinical setting.Approach From 2008-2012, an iterative, interactive process was used to develop the ECLS model and its core elements-patients and families informing process changes; trainees engaging both in care and the improvement of care; leaders knowing, valuing, and practicing improvement; data transforming into useful information; and health professionals competently engaging both in care improvement and teaching about care improvement. In 2012-2013, a three-part feasibility test of the model, including a site self-assessment, an independent review of each site's ratings, and implementation case stories, was conducted at six clinical teaching sites (in the United States and Sweden).Outcomes Site leaders reported the ECLS model provided a systematic approach toward improving patient (and population) outcomes, system performance, and professional development. Most sites found it challenging to incorporate the patients and families element. The trainee element was strong at four sites. The leadership and data elements were self-assessed as the most fully developed. The health professionals element exhibited the greatest variability across sites.Next Steps The next test of the model should be prospective, linked to clinical and educa tional outcomes, to evaluate whether it helps care delivery teams, educators, and patients and families take action to achieve better patient (and population) outcomes, system performance, and professional development.
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- Dand, Nick, et al.
(författare)
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Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling
- 2017
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Ingår i: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 26:21, s. 4301-4313
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.
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- Ferreira, Manuel A R, et al.
(författare)
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Eleven loci with new reproducible genetic associations with allergic disease risk.
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 691-699
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.OBJECTIVE: We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects.METHODS: We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study.RESULTS: Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10-6. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress TH2 responses.CONCLUSION: Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted.
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- Klebanoff, Mark A., et al.
(författare)
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Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis
- 2023
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Ingår i: Paediatric and Perinatal Epidemiology. - : WILEY. - 0269-5022 .- 1365-3016. ; 37:3, s. 239-251
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Forskningsöversikt (refereegranskat)abstract
- BackgroundBacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. ObjectivesDetermine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. Data SourcesCochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) ; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). Study Selection and Data ExtractionStudies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I-2. Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. ResultsThere were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I-2 = 62%, and 0.59 (95% CI 0.42, 0.82), I-2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I-2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I-2 = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. ConclusionsClindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.
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| 6. |
- Klein, G., et al.
(författare)
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Macrocognition
- 2003
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Ingår i: IEEE Intelligent Systems & Their Applications. - 1094-7167. ; 18:3, s. 81-85
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Forskningsöversikt (refereegranskat)abstract
- The importance of macrocognition in a cognitive system is discussed. Macrocognition is a term which indicates a level of description of the cognitive functions that are performed in natural decision-making settings. Macrocognition comprises the mental activities that must be successfully accomplished to perform a task or achieve a goal.
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