Publications by authors named "Aasne Karine Aarsand"

6 Publications

  • Page 1 of 1

Sick leave, disability, and mortality in acute hepatic porphyria: a nationwide cohort study.

Orphanet J Rare Dis 2020 02 21;15(1):56. Epub 2020 Feb 21.

Norwegian Organisation for Quality Improvement of Laboratory Examinations (NOKLUS), Haraldsplass Deaconess Hospital, Bergen, Norway.

Background: Acute hepatic porphyria (AHP) consists of three rare metabolic disorders. We investigated the risk of long-term sick leave, disability pension, and premature death in individuals with AHP compared to the general population.

Methods: In a nationwide cohort study from 1992 to 2017, records of 333 persons (total person-years = 6728) with a confirmed AHP diagnosis were linked to several national compulsory registries (reference population = 5,819,937). We conducted survival analyses to assess additional risk.

Results: Persons with AHP had higher risks of accessing long-term sick leave (adjusted hazard ratio (aHR): 1.5, 95% confidence interval (CI): 1.3, 1.7) and disability pension (aHR: 1.9, CI: 1.5, 2.4). The risk was highest in persons who had been hospitalised for acute attacks, while no additional risk was observed in asymptomatic AHP gene mutation carriers. The median age when accessing disability pension was 45 years, 21 years younger than the general population. AHP was associated with increased risk of mortality due to hepatocellular carcinoma (adjusted mortality rate ratio (aMRR): 84.4, CI: 37.8, 188.2), but no overall increased risk of premature death was observed.

Conclusions: Persons with symptomatic AHP were at increased risk of accessing long-term sick leave and disability pension but not of premature death.
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February 2020

Porphyria cutanea tarda increases risk of hepatocellular carcinoma and premature death: a nationwide cohort study.

Orphanet J Rare Dis 2019 04 3;14(1):77. Epub 2019 Apr 3.

Norwegian Quality Improvement of Laboratory Examinations (NOKLUS), Haraldsplass Deaconess Hospital, Bergen, Norway.

Background: Porphyria cutanea tarda (PCT) is a skin disorder originating from a deficit of the liver enzyme uroporphyrinogen decarboxylase. PCT may be a risk factor for hepatocellular carcinoma (HCC) and other cancers, but the evidence is unclear. We aimed to investigate cancer and premature mortality risk in persons with PCT.

Methods: The cohort study consisted of all Norwegian residents from 18 years between 2000 and 2016 (n = 5.4 million). 612 persons with PCT, and all cancer diagnoses and causes of death were identified through record linkage between national registries. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were adjusted for age, sex, education and calendar years. We additionally compared persons with PCT to persons with a history of chronic alcohol abuse (n = 30,468).

Results: Persons with PCT were more likely to be diagnosed with HCC [adjusted HR (aHR) = 19.7, CI = 8.8-44.0) and gallbladder and biliary tract cancer (aHR = 6.8, CI = 2.2-21.0) than the reference population. A moderate increased risk for HCC (aHR = 3.1, CI = 1.2-7.7) and gallbladder and biliary tract cancer (aHR = 4.0, CI = 1.1-14.4) remained when compared to persons with a history of chronic alcohol abuse. Additionally, compared to the reference population, persons with PCT had an increased risk of premature death (aHR = 1.5, CI = 1.2-1.7), due to the following causes of death: malignant neoplasms (aHR = 1.4, CI = 1.0-1.9), diseases of the liver (HR = 5.5, CI = 2.5-12.2), and drug and alcohol overdose (HR = 9.9, CI = 4.7-20.8).

Conclusions: Persons with PCT had an increased risk of HCC and cancer of the gallbladder and biliary tract, as well as premature death. Although most of our findings can likely be explained by common lifestyle risk factors, something inherent in PCT may contribute to the development of HCC.
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April 2019

The EuBIVAS Project: Within- and Between-Subject Biological Variation Data for Serum Creatinine Using Enzymatic and Alkaline Picrate Methods and Implications for Monitoring.

Clin Chem 2017 Sep 18;63(9):1527-1536. Epub 2017 Jul 18.

Central Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.

Background: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined biological variation (BV) indices. EuBIVAS determined BV for serum creatinine using the enzymatic and alkaline picrate measurement methods.

Method: In total, 91 healthy individuals (38 males, 53 females; age range, 21-69 years) were bled for 10 consecutive weeks at 6 European laboratories. An equivalent protocol was followed at each center. Sera were stored at -80 °C before analysis. Analyses for each patient were performed in duplicate within a single run on an ADVIA 2400 system (San Raffaele Hospital, Milan). The data were subjected to outlier and homogeneity analysis before performing CV-ANOVA to determine BV and analytical variation (CV) estimates with confidence intervals (CI).

Results: The within-subject BV estimates [CV (95% CI)] were similar for enzymatic [4.4% (4.2-4.7)] and alkaline picrate [4.7% (4.4-4.9)] methods and lower than the estimate presently available online (CV = 5.9%). No significant male/female BV differences were found. Significant differences were observed in mean creatinine values between men and women and between Turkish individuals and those of other nationalities. Between-subject BV (CV) estimates, stratified accordingly, produced CV values similar to historical BV data. CV was 1.1% for the enzymatic and 4.4% for alkaline picrate methods, indicating that alkaline picrate methods fail to fulfill analytical performance specifications for imprecision (CV).

Conclusions: The serum creatinine CV obtained by EuBIVAS specifies a more stringent CV than previously identified. The alkaline picrate method failed to meet this CV, raising questions regarding its future use.
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September 2017

Porphyrias in Norway.

Tidsskr Nor Laegeforen 2014 Apr 29;134(8):831-6. Epub 2014 Apr 29.

Nasjonalt kompetansesenter for porfyrisykdommer (NAPOS) Laboratorium for klinisk biokjemi Haukeland universitetssykehus.

Background: Porphyria is an umbrella term for a group of largely hereditary diseases that are due to defective haem synthesis. The diseases have a varied and partly overlapping range of symptoms and presentations. The commonest forms of porphyria are porphyria cutanea tarda, acute intermittent porphyria and erythropoietic protoporphyria. The purpose of this study is to provide an overview of the prevalence and pathological manifestations of porphyrias in Norway.

Material And Method: Information on all patients registered with the Norwegian Porphyria Centre (NAPOS) up to 2012 was used to estimate the prevalence and incidence of porphyrias in Norway. Figures on symptoms, precipitating factors and follow-up routines were obtained from the Norwegian Porphyria Registry, which includes 70% of Norwegians registered with NAPOS as having porphyria.

Results: The prevalence of porphyria cutanea tarda was approximately 10 : 100,000 and that of acute intermittent porphyria approximately 4 : 100,000. The total incidence of all porphyrias was approximately 0.5-1 : 100,000 per year. Diagnostic delay, i.e. the time passing between the onset of symptoms and diagnosis, varied from 1-17 years depending on the type of porphyria. There was wide variation in the frequency with which patients with the various types of porphyria went for medical check-ups.

Interpretation: The prevalence of acute intermittent porphyria and porphyria cutanea tarda appears to be higher in Norway than in most other countries. Data from the Norwegian Porphyria Registry makes it possible to demonstrate differences in treatment and follow-up of porphyria patients and may be used to initiate necessary measures.
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April 2014

Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study.

J Inherit Metab Dis 2011 Feb 27;34(1):217-23. Epub 2010 Oct 27.

The Norwegian Porphyria Centre (NAPOS), Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.

The porphyrias comprise a heterogeneous group of rare, primarily hereditary, metabolic diseases caused by a partial deficiency in one of the eight enzymes involved in the heme biosynthesis. Our aim was to assess whether acute or cutaneous porphyria has been associated with excess risks of adverse pregnancy outcomes. A population-based cohort study was designed by record linkage between the Norwegian Porphyria Register, covering 70% of all known porphyria patients in Norway, and the Medical Birth Registry of Norway, based on all births in Norway during 1967-2006. The risks of the adverse pregnancy outcomes preeclampsia, delivery by caesarean section, low birth weight, premature delivery, small for gestational age (SGA), perinatal death, and congenital malformations were compared between porphyric mothers and the rest of the population. The 200 mothers with porphyria had 398 singletons during the study period, whereas the 1,100,391 mothers without porphyria had 2,275,317 singletons. First-time mothers with active acute porphyria had an excess risk of perinatal death [adjusted odds ratio (OR) 4.9, 95% confidence interval (CI) 1.5-16.0], as did mothers with the hereditable form of porphyria cutanea tarda (PCT) (3.0, 1.2-7.7). Sporadic PCT was associated with an excess risk of SGA [adjusted relative risk (RR) 2.0, 1.2-3.4], and for first-time mothers, low birth weight (adjusted OR 3.4, 1.2-10.0) and premature delivery (3.5, 1.2-10.5) in addition. The findings suggest women with porphyria should be monitored closely during pregnancy.
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February 2011

'Likelihood-ratio' and 'odds' applied to monitoring of patients as a supplement to 'reference change value' (RCV).

Clin Chem Lab Med 2008 ;46(2):157-64

NOKLUS, Norwegian Quality Improvement of Primary Care Laboratories, Division for General Practice, University of Bergen, Bergen, Norway.

Background: Interpretation of serial data in monitoring of patients is usually performed by use of the 'reference change value' (RCV). While this tool for interpretation of measured differences is simple and clear, there are a number of drawbacks attached to the uncritical use of this concept. It is a dichotomised interpretation of continuous data using a fixed probability without any counter hypothesis. Therefore, a tool for better understanding and interpretation of measured differences in monitoring is needed.

Theory: The concept of sensitivity, specificity, likelihood ratios and odds used for diagnostic test evaluations is applied to monitoring by substituting measured concentrations with measured differences. Thus, two frequency distributions of differences are assumed, one for a stable, steady-state, situation and one for a certain change. Values exceeding a measured difference will thus represent 'false change' for the stable and 'true change' for the change and the ratio between these will define the likelihood. By making the hypothesis of change variable and equal to the actual difference, the distribution corresponding to the true changes for the measured difference varies with this. Consequently, the likelihood ratio for change increases with growing measured difference and when used together with the pre-test odds or pre-test probability, the post-test odds and post-test probability, related to the clinical situation, can be calculated.

Results: One example is acute intermittent porphyria, where increasing excretion of porphobilinogen is characteristic for an attack. The within-subject biological variation is estimated to 25%, which for two measurements gives a variation of 35% for measured differences. Three pre-test probabilities are assumed and illustrate that post-test odds and probability depends on both the pre-test probability and the measured difference. A second example is monitoring women in a follow-up after treatment of breast cancer, using the tumour marker CA 15-3. The within-subject biological variation is estimated to 14.9% and for differences 21% (2(1/2) x 14.9 due to two measurements). Here, the monitoring is totally scheduled and the frequency of progression depends on the time after treatment. Thus, the pre-test probability varies with time so that a certain measured difference with a given likelihood ratio will result in varying post-test odds depending on time.

Conclusions: The concept presented here expands the earlier concept of RCVs by making it possible to have an estimate of the post-test odds for a certain difference to occur based on likelihood ratios and pre-test odds.
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May 2008