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Hirsla is an open access repository, designed as a place to store, index, preserve and redistribute in digital format scholarly work of Landspitali employees. (A/H1N1)

  • Association of polypharmacy and hyperpolypharmacy with frailty states: a systematic review and meta-analysis

    Palmer, Katie; Villani, Emanuele R; Vetrano, Davide L; Cherubini, Antonio; Cruz-Jentoft, Alfonso J; Curtin, Denis; Denkinger, Michael; Gutierrez-Valencia, Marta; Gudmundsson, Adalsteinn; et al; [ 1 ] IRCCS, Fdn Osped San Camillo, Via Alberoni 70, I-30126 Venice, Italy Show more [ 2 ] Univ Cattolica Sacro Cuore, Ctr Med Invecchiamento, Dept Geriatr, Rome, Italy Show more [ 3 ] Karolinska Inst, NVS, Aging Res Ctr, Stockholm, Sweden Show more [ 4 ] IRCCS, INRCA, Accettaz Geriatr Ctr Ric Invecchiamento, Geriatr, Ancona, Italy Show more [ 5 ] Hosp Univ Ramon y Cajal, Serv Geriatr, Madrid, Spain Show more [ 6 ] Cork Univ Hosp, Univ Coll Cork, Dept Geriatr Med, Dept Med, Cork, Ireland Show more [ 7 ] Ulm Univ, Geriatr Ctr Ulm, Alb Donau & Geriatr Res Unit, Agaples Bethesda Clin Ulm, Ulm, Germany Show more [ 8 ] Univ Publ Navarra UPNA, CHN, Dept Pharm, Navarrabiomed, Navarra, Spain Show more [ 9 ] Univ Iceland, Fac Med, Reykjavik, Iceland Show more [ 10 ] Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland Show more [ 11 ] Univ Utrecht, Univ Med Ctr Utrecht, Expertise Ctr Pharmacotherapy Old Persons, Dept Geriatr Med, Utrecht, Netherlands Show more [ 12 ] Heidelberg Univ, Med Fac Mannheim, Inst Clin Pharmacol, Mannheim, Germany Show more [ 13 ] Univ Ghent, Sect Geriatr, Dept Internal Med, Ghent, Belgium Show more [ 14 ] Univ Sussex, Brighton & Sussex Med Sch, Dept Med, Brighton, E Sussex, England Show more [ 15 ] Charles Univ Prague, Gen Fac Hosp, Dept Geriatr, Fac Med 1, Prague, Czech Republic Show more [ 16 ] Univ Padua, Geriatr Div, Dept Med, Padua, Italy Show more [ 17 ] Delft Univ Technol, Fac Ind Design Engn, Delft, Netherlands Show more [ 18 ] Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Div Geriatr, Rotterdam, Netherlands Show more [ 19 ] Brighton & Sussex Med Sch, Acad Dept Geriatr, Brighton, E Sussex, England Show more [ 20 ] Vrije Univ Amsterdam, Amsterdam UMC, Dept Gen Practice & Old Age Med, Amsterdam, Netherlands Show more [ 21 ] Jeroen Bosch Hosp, Dept Geriatr, Shertogenbosch, Netherlands Show more [ 22 ] Heidelberg Univ, Clin Pharmacol, Med Fac Mannheim, Heidelberg, Germany (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.

    Briem, Eirikur; Budkova, Zuzana; Sigurdardottir, Anna Karen; Hilmarsdottir, Bylgja; Kricker, Jennifer; Timp, Winston; Magnusson, Magnus Karl; Traustadottir, Gunnhildur Asta; Gudjonsson, Thorarinn; 1 Stem Cell Research Unit, Biomedical Center, Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland. 2 Stem Cell Research Unit, Biomedical Center, Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland; Department of Tumor Biology, The Norwegian Radium Hospital, Oslo, Norway. 3 Department of Biomedical Engineering, Johns Hopkins University, USA. 4 Department of Laboratory Hematology, Landspitali - University Hospital, Iceland; Department of Pharmacology and Toxicology, Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland. 5 Stem Cell Research Unit, Biomedical Center, Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland; Department of Laboratory Hematology, Landspitali - University Hospital, Iceland. Electronic address: tgudjons@hi.is. (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.

    Gudmundsson, Haukur T; Hansen, Karen E; Halldorsson, Bjarni V; Ludviksson, Bjorn R; Gudbjornsson, Bjorn; 1 Department of Medicine, Landspitali - University Hospital, Reykjavik, Iceland. haukurtg@icloud.com. 2 Rheumatology Division, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, USA. 3 School of Science and Engineering, Reykjavik University, Reykjavik, Iceland. 4 Immunology and Centre for Rheumatology Research, Reykjavik, Iceland. 5 The Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 6 Landspitali - University Hospital, Reykjavik, Iceland. (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.

    Hruskova, Zdenka; Pippias, Maria; Stel, Vianda S; Abad-Díez, Jose M; Benítez Sánchez, Manuel; Caskey, Fergus J; Collart, Frederic; De Meester, Johan; Finne, Patrik; Heaf, James G; Magaz, Angela; Palsson, Runolfur; Reisæter, Anna Varberg; Salama, Alan D; Segelmark, Mårten; Traynor, Jamie P; Massy, Ziad A; Jager, Kitty J; Tesar, Vladimir; 1 Department of Nephrology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. 2 ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, Amsterdam Public Health Research Institute, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: m.pippias@amc.nl. 3 ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, Amsterdam Public Health Research Institute, University of Amsterdam, Amsterdam, the Netherlands. 4 Renal Registry of Aragon, Aragon Health Service, Aragon, Spain. 5 Hospital Juan Ramón Jiménez, Huelva, Andalusia, Spain. 6 UK Renal Registry, Southmead Hospital, Bristol, United Kingdom; Population Health Sciences, University of Bristol, Bristol, United Kingdom. 7 French-Belgian ESRD Registry, Brussels, Belgium. 8 Department of Nephrology, Dialysis and Hypertension, Dutch-speaking Belgian Renal Registry (NBVN), Sint-Niklaas, Belgium. 9 Department of Nephrology, Helsinki University and Helsinki University Hospital, Helsinki, Finland; Finnish Registry for Kidney Diseases, Helsinki, Finland. 10 Department of Medicine, Zealand University Hospital, Roskilde, Denmark. 11 Unidad de Información sobre Pacientes Renales de la Comunidad Autónoma del País Vasco (UNIPAR), Basque Country, Spain. 12 Division of Nephrology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 13 Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Norway. 14 University College London Centre for Nephrology, Royal Free Hospital, London, United Kingdom. 15 Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Department of Nephrology, Linköping University, Linköping, Sweden. 16 Scottish Renal Registry, ISD Scotland, Glasgow, Scotland. 17 Division of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt; Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Team 5, CESP UVSQ, and University Paris Saclay, Villejuif, France. (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.

    Højfeldt, Sofie G; Wolthers, Benjamin O; Tulstrup, Morten; Abrahamsson, Jonas; Gupta, Ramneek; Harila-Saari, Arja; Heyman, Mats; Henriksen, Louise T; Jónsson, Òlafur G; Lähteenmäki, Päivi M; Lund, Bendik; Pruunsild, Kaie; Vaitkeviciene, Goda; Schmiegelow, Kjeld; Albertsen, Birgitte K; 1 Child and Adolescent Health, Aarhus University Hospital, Aarhus, Denmark. 2 Department of Paediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark. 3 Department of Paediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 4 Department of Bio- and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark. 5 Department of Women's and Children's health, Uppsala University, Uppsala, Sweden. 6 Department of Women's and Children's health, Childhood Cancer Research Unit, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden. 7 Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. 8 Department of Paediatric and Adolescent Medicine, Turku University Hospital and Turku University, Turku, Finland. 9 Department of Paediatrics, St. Olavs Hospital, Trondheim, Norway. 10 Department of Oncology and Haematology, University Children's Hospital, Tallinn, Estonia. 11 Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. (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

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