Levinsen M.,Copenhagen University |
Rosthoj S.,Copenhagen University |
Nygaard U.,Copenhagen University |
Heldrup J.,Skane University Hospital |
And 8 more authors.
Cancer Chemotherapy and Pharmacology
Purpose: Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMTIA) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT.Methods: Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy.Results: The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However, since TPMTIA had lower blood counts at initiation of HD-MTX compared with TPMTHA patients (median WBC 2.8 vs. 3.3 × 109/L, P = 0.01; median ANC 1.4 vs. 1.7 × 109/L, P = 0.02), TPMTIA continued to have lower WBC and ANC levels compared with TPMTHA during all 28 days after HD-MTX [relative difference 9 % (95 % CI 2–17), P = 0.02 and 21 % (95 % CI 6–39), P = 0.005]. Still, the fractional decrease in WBC and ANC levels after HD-MTX did not differ between TPMTIA and TPMTHA patients (P = 0.47; P = 0.38). The degree of leukopenia, neutropenia, thrombocytopenia and rise in aminotransferases were all significantly related to 6MP dose (P < 0.001 for all analyses).Conclusion: For both TPMTIA and TPMTHA patients, dose of 6MP prior to HD-MTX should be guided by pre-HD-MTX blood counts, but not by TPMT activity. © 2014 Springer-Verlag Berlin Heidelberg Source
Gunnarsson B.,Norwegian Air Ambulance Foundation |
Jensen N.S.K.,Rigshospitalet |
Gardi T.I.,Landssjukrahusid |
Hardardottir H.,Landspitali |
And 2 more authors.
International Journal of Circumpolar Health
The Nordic Atlantic Cooperation (NORA) is an intergovernmental organization under the auspices of the Nordic Council of Ministers. The NORA region comprises Greenland, Iceland, Faroe Islands and western coastal areas of Norway. Historical, cultural and institutional links bind these nations together in multiple ways, and regional co-operation has in recent years become a focus of interest. This commentary addresses air medical services (AMSs) and available advanced hospital services in the 3 smallest NORA countries challenged sparse populations, hereafter referred to as the region. It seems likely that strengthened regional co-operation can help these countries to address common challenges within health care by exchanging know-how and best practices, pooling resources and improving the efficiency of care delivery. The 4 largest hospitals in the region, Dronning Ingrids Hospital in Nuuk (Greenland), Landspítali in Reykjavík and Sjúkrahúsið á Akureyri, (both in Iceland) and Landssjúkrahú sið Tórshavn on the Faroe Islands, have therefore undertaken the project Network for patient transport in the North-West Atlantic (in Danish: Netværk for patienttransport i Vest-Norden). The goal of the project, and of this article, is to exchange information and provide an overviewof current AMSs and access to acute hospital care for severely ill or injured patients in the 3 participating countries. Of equal importance is the intention to highlight the need for increased regional co-operation to optimize use of limited resources in the provision of health care services. © 2015 Björn Gunnarsson et al. Source
Olafsson G.B.,University of Iceland |
Steingrimsdottir H.,Landspitali |
Introduction: Chronic lymphocytic leukemia (CLL) is characterized by the proliferation of monoclonal B-lymphocytes. MBL (monoclonal B-cell lymphocytosis) is considered a precursor state of the disease. Although CLL is incurable it is an indolent disorder and often detected incidentally on routine blood counts. Until now little information has been available on CLL in Iceland, including the incidence, diagnosis, symptoms or MBL precursor state. Material and methods: This is a retrospective, descriptive study including CLL patients diagnosed in Iceland over the years 2003-2013. Registries of patients with a CLL diagnosis were obtained from the Icelandic Cancer Registry, Landspitali National University Hospital and the Medical Center in Mjódd. Medical records were reviewed for information on symptoms, diagnosis and treatment. Survival data and causes of death were obtained from national registries. Results: The number of patients diagnosed with CLL over the study period was 161 (109 males, 52 females). The calculated incidence was 4.55/100,000, and the age-standardized incidence was 3.00/100,000. Mean age at diagnosis was 70.9 years (range 35-96 years). The Icelandic Cancer Registry lacked information on 28 patients (17.4%). The initial diagnosis of CLL was obtained exclusively with flow cytometry in 47.2% of cases. Symptoms were present at diagnosis in 67 of 151 patients (44.4%). One third of the group received chemotherapy and the average time to treatment was 1.3 years. Five-year survival was 70% and median survival was 9.4 years. Elevated lymphocyte counts (≥4,0×109/L) in peripheral blood prior (0.1 to 13.4 years) to diagnosis of CLL was identified in 85 of 99 CLL patients (85.9%). Conclusion: The incidence of CLL in Iceland is similar to other Western countries. The registration of CLL cases in the Icelandic Cancer Registry must be improved, especially in cases where diagnosis is based solely on flow cytometry. Elevated lymphocyte counts were present in a large proportion of cases prior to the diagnosis of CLL. Source
Petursson P.,Reykjavik University |
Edmunds K.J.,Reykjavik University |
Gislason M.K.,Reykjavik University |
Magnusson B.,Reykjavik University |
And 5 more authors.
Computational and Mathematical Methods in Medicine
The variability in patient outcome and propensity for surgical complications in total hip replacement (THR) necessitates the development of a comprehensive, quantitative methodology for prescribing the optimal type of prosthetic stem: cemented or cementless. The objective of the research presented herein was to describe a novel approach to this problem as a first step towards creating a patient-specific, presurgical application for determining the optimal prosthesis procedure. Finite element analysis (FEA) and bone mineral density (BMD) calculations were performed with ten voluntary primary THR patients to estimate the status of their operative femurs before surgery. A compilation model of the press-fitting procedure was generated to define a fracture risk index (FRI) from incurred forces on the periprosthetic femoral head. Comparing these values to patient age, sex, and gender elicited a high degree of variability between patients grouped by implant procedure, reinforcing the notion that age and gender alone are poor indicators for prescribing prosthesis type. Additionally, correlating FRI and BMD measurements indicated that at least two of the ten patients may have received nonideal implants. This investigation highlights the utility of our model as a foundation for presurgical software applications to assist orthopedic surgeons with selecting THR prostheses. © 2015 Pröstur Pétursson et al. Source
Perner A.,Copenhagen University |
Haase N.,Copenhagen University |
Guttormsen A.B.,University of Bergen |
Tenhunen J.,University of Tampere |
And 29 more authors.
New England Journal of Medicine
BACKGROUND: Hydroxyethyl starch (HES) 130/0.42 is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS: In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P = 0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P = 0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P = 0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS: Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.) Copyright © 2012 Massachusetts Medical Society. Source