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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.
Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe: Results From the ERA-EDTA Registry.(W.B. Saunders, 2019-02-01)Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT. Registry study of incidence and prevalence and a matched cohort study of clinical outcomes. Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and 2013. Scleroderma as the identified cause of ESRD.
Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008.(Wiley, 2019-02-01)Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10