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A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis.(Nature Publishing Group, 2019-01-01)Nasal polyps (NP) are lesions on the nasal and paranasal sinus mucosa and are a risk factor for chronic rhinosinusitis (CRS). We performed genome-wide association studies on NP and CRS in Iceland and the UK (using UK Biobank data) with 4,366 NP cases, 5,608 CRS cases, and >700,000 controls. We found 10 markers associated with NP and 2 with CRS. We also tested 210 markers reported to associate with eosinophil count, yielding 17 additional NP associations. Of the 27 NP signals, 7 associate with CRS and 13 with asthma. Most notably, a missense variant in ALOX15 that causes a p.Thr560Met alteration in arachidonate 15-lipoxygenase (15-LO) confers large genome-wide significant protection against NP (P = 8.0 × 10
Who are the main medical care providers of European nursing home residents? An EuGMS survey(Springer, 2019-02)IntroductionNursing home residents are complex, vulnerable and have been historically neglected. The EuGMS is committed to improving their care, and is currently developing a curriculum of core competencies. Integral to these efforts is identifying the physicians, for whom, education in these competencies needs to be directed.MethodA survey was distributed to European national geriatrics societies, asking members their perceptions of proportions of nursing home medical care delivered by various physician specialties, and the main functions carried out in nursing homes.ResultsResponses were received from 22 of 32 national geriatrics societies. The vast majority of care (estimated at 69%), is delivered by general practitioners, rather than geriatricians or specialist nursing home physicians. Nursing homes have acquired important roles in rehabilitation, respite and palliative care.ConclusionEducation and training to achieve the highest standards of care must be designed for general practitioners who do not have specialist training. Education and infrastructure must be developed for the evolving roles of nursing homes.
Association of polypharmacy and hyperpolypharmacy with frailty states: a systematic review and meta-analysis(Springer, 2019-02)PurposeTo investigate: (1) the cross-sectional association between polypharmacy, hyperpolypharmacy and presence of prefrailty or frailty; (2) the risk of incident prefrailty or frailty in persons with polypharmacy, and vice versa.MethodsA systematic review and meta-analysis was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/1998 to 5/2/2018. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I-2 statistic and publication bias with Egger's and Begg's tests.ResultsThirty-seven studies were included. The pooled proportion of polypharmacy in persons with prefrailty and frailty was 47% (95% CI 33-61) and 59% (95% CI 42-76), respectively. Increased odds ratio of polypharmacy were seen for prefrail (pooled OR=1.52; 95% CI 1.32-1.79) and frail persons (pooled OR=2.62, 95% CI 1.81-3.79). Hyperpolypharmacy was also increased in prefrail (OR=1.95; 95% CI 1.41-2.70) and frail (OR=6.57; 95% CI 9.57-10.48) persons compared to robust persons. Only seven longitudinal studies reported data on the risk of either incident prefrailty or frailty in persons with baseline polypharmacy. A significant higher odds of developing prefrailty was found in robust persons with polypharmacy (pooled OR=1.30; 95% CI 1.12-1.51). We found no papers investigating polypharmacy incidence in persons with prefrailty/frailty.ConclusionsPolypharmacy is common in prefrail and frail persons, and these individuals are also more likely to be on extreme drug regimens, i.e. hyperpolypharmacy, than robust older persons. More research is needed to investigate the causal relationship between polypharmacy and frailty syndromes, thereby identifying ways to jointly reduce drug burden and prefrailty/frailty in these individuals.Prospero registration numberCRD42018104756.
MiR-203a is differentially expressed during branching morphogenesis and EMT in breast progenitor cells and is a repressor of peroxidasin.(Elsevier Science, 2019-01-01)MicroRNAs regulate developmental events such as branching morphogenesis, epithelial to mesenchymal transition (EMT) and its reverse process mesenchymal to epithelial transition (MET). In this study, we performed small RNA sequencing of a breast epithelial progenitor cell line (D492), and its mesenchymal derivative (D492M) cultured in three-dimensional microenvironment. Among the most downregulated miRNAs in D492M was miR-203a, a miRNA that plays an important role in epithelial differentiation. Increased expression of miR-203a was seen in D492, concomitant with increased complexity of branching. When miR-203a was overexpressed in D492M, a partial reversion towards epithelial phenotype was seen. Gene expression analysis of D492M and D492M
Clinical decision support system for the management of osteoporosis compared to NOGG guidelines and an osteology specialist: a validation pilot study.(BioMed Central, 2019-02-01)Although osteoporosis is an easily diagnosed and treatable condition, many individuals remain untreated. Clinical decision support systems might increase appropriate treatment of osteoporosis. We designed the Osteoporosis Advisor (OPAD), a computerized tool to support physicians managing osteoporosis at the point-of-care. The present study compares the treatment recommendations provided by OPAD, an expert physician and the National Osteoporosis Guideline Group (NOGG). We performed a retrospective analysis of 259 patients attending the outpatient osteoporosis clinic at the University Hospital in Iceland. We entered each patient's data into the OPAD and recorded the OPAD diagnostic comments, 10-year risk of major osteoporotic fracture and treatment options. We compared OPAD recommendations to those given by the osteoporosis specialist, and to those of the NOGG. Risk estimates made by OPAD were highly correlated with those from FRAX (r = 0.99, 95% CI 0.99, 1.00 without femoral neck BMD; r = 0.98, 95% CI, 0.97, 0.99 with femoral neck BMD. Reassurance was recommended by the expert, NOGG and the OPAD in 68, 63 and 52% of cases, respectively. Likewise, intervention was recommended by the expert, NOGG, and the OPAD in 32, 37 and 48% of cases, respectively. The OPAD demonstrated moderate agreement with the physician (kappa 0.51, 95% CI 0.41, 0.61) and even higher agreement with NOGG (kappa 0.69, 95% CI 0.60, 0.77). Primary care physicians can use the OPAD to assess and treat patients' skeletal health. Recommendations given by OPAD are consistent with expert opinion and existing guidelines.