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- Arbring, Kerstin, 1961-
(författare)
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Two worlds, one goal : A Clinician’s Perspective on Laboratory Analyses in Anticoagulant Treatment
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Almost precisely a century ago, in the 1920s and 1930s, cattle bled to death in North America after being fed moldy hay containing sweet clover, the yellow Melilotus officinalis, and the white Melilotus albus. The toxic substance in the hay inhibiting blood coagulation was identified and named dicumarol. Further development resulted in warfarin, an oral anticoagulant that has been used for over 70 years and still is, even though newer direct-acting oral anticoagulants (DOACs) are mainly replacing it. For some patients, warfarin is still the drug of choice. A safe warfarin treatment needs repeated blood sample analysis (PT-INR), and with the new DOACs come new laboratory challenges. The aim of this thesis was to investigate ways laboratory methods can contribute to improving oral anticoagulant treatment. Paper I explores genetic variants of the enzyme targeted by warfarin, VKORC1. The result shows that the haplotype VKORC1*2 is the most important of the VKORC1 haplotypes for warfarin dosage, with a lower dose requirement. The VKORC1*2 haplotype was also related to more unstable PT-INR levels. Paper II describes a cross-section study comparing warfarin treatment control, as PT-INRs within the intended therapeutic range, in primary health care centers (PHCCs) and specialized anticoagulation clinics (ACCs). Both settings showed good therapeutic control, with at least as good therapeutic control in the PHCCs as in the ACCs. Today, almost all warfarin treatment in our region is centralized to ACCs. Paper III focuses on the modification of a point-of-care PT method. A ratio of PT from two different dilutions of each patient sample was calculated and used as an indirect measure of DOAC activity. There were close correlations between the PT ratio and drug concentrations measured at the hospital laboratory. The detection level varies between DOACs and may limit its use in some situations. Paper IV evaluated the MRX PT DOAC, an assay based on the PT ratio principle. It was found to be able to detect potentially interfering DOAC levels in plasma samples. Confirmatory testing is recommended, as is sensitivity improvement for the detection of specific interferences.
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| 2. |
- Austeng, Dordi, et al.
(författare)
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Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
- 2010
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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| 3. |
- Austeng, Dordi, et al.
(författare)
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Incidence of retinopathy of prematurity in infants born before 27 weeks' gestation in Sweden
- 2009
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Ingår i: Archives of ophthalmology (1960). - : American Medical Association (AMA). - 0003-9950. ; 127:10, s. 1315-1319
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the incidence of retinopathy of prematurity (ROP) in extremely preterm infants born before 27 weeks' gestation in Sweden during a 3-year period. METHODS: A national, prospective, population-based study was performed in Sweden from April 1, 2004, to March 31, 2007. The ophthalmologic part of the study was separately organized, and screening for ROP was performed beginning postnatal week 5. The criteria for the treatment of ROP agreed with the recommendations of the Early Treatment for Retinopathy of Prematurity Cooperative Group. RESULTS: During the study, 506 of 707 live-born infants survived until the first eye examination. Of these, 368 (72.7%) had ROP: 37.9% had mild ROP and 34.8% had severe ROP. Ninety-nine infants (19.6%) were treated. Gestational age at birth was a stronger predictor of ROP than was birth weight. A log-linear relationship between severe ROP and gestational age at birth was found in the present cohort, and the risk of ROP was reduced by 50% for each week of increase in gestational age at birth. CONCLUSIONS: Today, extremely preterm infants are surviving, and this population-based study with ROP as a primary outcome shows a higher incidence of this condition than in previously reported national cohorts.
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| 4. |
- Austeng, Dordi, et al.
(författare)
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Natural history of retinopathy of prematurity in infants born before 27 weeks' gestation in Sweden
- 2010
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Ingår i: Archives of ophthalmology (1960). - : American Medical Association. - 0003-9950. ; 128:10, s. 1289-1294
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the natural history of retinopathy of prematurity (ROP) in 506 extremely preterm infants born before 27 weeks' gestation in Sweden during a 3-year period. Methods: A national population–based study was performed in Sweden from April 1, 2004, to March 31, 2007. According to the study protocol, initial eye examinations were to be performed at postnatal week 5, and examinations were repeated until the retina was completely vascularized or until criteria for treatment were met. The examinations were to be performed weekly, enabling study of the course and severity of ROP. In infants without ROP or with mild ROP without progression during the latest examinations, further examinations were performed weekly or every other week from postmenstrual age 35 weeks. Results: During the study, 368 infants (72.7%) developed ROP. Postmenstrual age at onset of ROP was significantly related to severity of ROP, even when controlling for gestational age (ie, the earlier the onset of ROP, the higher the risk of developing severe ROP). Site of onset of ROP was significantly related to gestational age at birth. The risk of nasal onset was almost doubled for every week of decrease in gestational age at birth. Nasal onset was associated with severe ROP, even after adjusting for gestational age at birth. Conclusion: This population-based study confirms results of the Cryotherapy for Retinopathy of Prematurity study and shows new correlations regarding time and site of onset of ROP, both of which are associated with disease severity.
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| 5. |
- Austeng, Dordi, et al.
(författare)
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Regional differences in screening for retinopathy of prematurity in infants born before 27 weeks of gestation in Sweden : the EXPRESS study
- 2014
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Ingår i: Acta Ophthalmologica. - : Wiley-Blackwell. - 1755-375X .- 1755-3768. ; 92:4, s. 311-315
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The primary aim was to analyse regional incidences of retinopathy of prematurity (ROP) and frequencies of treatment and their relation to perinatal risk factors during a 3-year period. A secondary aim was to study adherence to the study screening protocol in the different regions.Methods: A population-based study of neonatal morbidity in extremely preterm infants in Sweden (EXPRESS) was performed during 2004-2007. Screening for ROP was to start at postnatal age 5weeks and to continue weekly until the retina was completely vascularized or until regression of ROP. Logistic regression analyses were used for evaluation of differences in incidence of Any ROP, ROP 3 or more and ROP Type 1 between the seven regions of the country.Results: The regional incidence of ROP varied between 54% and 92% for Any ROP, between 25% and 43% for ROP stage 3 or more and between 8% and 23% of infants with ROP Type 1, all of whom were treated. There was no significant difference between the regions regarding ROP Type 1, even when adjusting for known risk factors for ROP.Conclusion: The heterogeneity between the regions regarding the incidence of ROP was reduced with increasing severity of ROP, and there was no heterogeneity regarding frequency of treatment for ROP, which is the most important issue for the children. We cannot exclude observer bias regarding mild ROP and ROP stage 3 in this study.
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| 6. |
- Austeng, Dordi
(författare)
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Retinopathy of Prematurity in Infants Born Before 27 Weeks of Gestation : A National Population-based Study in Sweden During 2004-2007
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Improved neonatal care has resulted in an increasing population of surviving infants. Neonatal morbidity in preterm infants is, however, high, and retinopathy of prematurity (ROP) is one of the major neonatal morbidities. Observations have suggested that ROP might have a different course in extremely preterm compared to more mature infants. Aims: To study the incidence, natural history and treatment of the disease, and the implications regarding screening recommendations for the population of extremely preterm infants. Methods: A national, population-based study of neonatal morbidity in infants born before 27 gestational weeks was performed in Sweden during 2004 to 2007. ROP screening started in the 5th postnatal week and continued until the retina was completely vascularized. Results: Of the 506 infants surviving until the first ROP examination, 73% developed ROP; 38% mild ROP and 35% severe ROP. Ninety-nine infants (20%) were treated. A log-linear relationship was found between severe ROP and gestational age (GA) at birth, and the risk of ROP was reduced by 50% for each week of increase in GA at birth (Paper I). Postmenstrual age (PMA) at onset of ROP was significantly related to GA at birth, as was the site of onset of ROP. ROP had a predilection to start in the nasal retina in the most immature infants. There were significant relations between PMA at onset of ROP and severity of ROP as well as between the site of onset of ROP and severe ROP (Paper III). The most immature infants had a higher risk of reaching treatment criteria for ROP, a higher risk of progression from ROP 3 to treatment criteria, and they reached these criteria at an earlier PMA than the less immature infants (Paper II). According to our results, the first examination can be postponed until a PMA of 31 weeks in infants born before 27 weeks of gestation, since onset of ROP 3 did not occur before this age, and criteria for treatment were not reached before 32 weeks. The majority of infants (75%) were treated during a limited period, i.e. before a PMA of 39 weeks (Paper IV).
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| 7. |
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| 8. |
- Austeng, Dordi, et al.
(författare)
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Treatment for retinopathy of prematurity in infants born before 27 weeks of gestation in Sweden
- 2010
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Ingår i: British Journal of Ophthalmology. - : BMJ. - 0007-1161 .- 1468-2079. ; 94:9, s. 1136-1139
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To study various aspects of treatment for retinopathy of prematurity (ROP) in a Swedish population of extremely preterm infants born before 27 weeks of gestation. METHODS: A national, prospective and population-based study was performed in Sweden from April 1, 2004 to March 31, 2007. The criteria for treatment of ROP accorded with the recommendations of the Early Treatment for Retinopathy of Prematurity Cooperative Group. RESULTS: Twenty percent of the infants (99/506) were treated for ROP. The likelihood of reaching treatment criteria nearly doubled for each week of reduction in gestational age (GA) at birth. The first treatment was performed at an earlier postmenstrual age in the most immature infants. One third of the infants had more than one session of laser treatment. CONCLUSIONS: A high percentage of these extremely preterm infants required treatment for ROP. The likelihood of reaching treatment criteria increased with a decline in GA at birth. Although only a few infants progressed to ROP Stages 4 and 5, our findings indicate a potential for improvement of the treatment routines, both regarding timing and number of laser spots at the first treatment.
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| 9. |
- Bonamy, Anna-Karin E., et al.
(författare)
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Preterm Birth and Later Retinal Detachment
- 2013
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Ingår i: Ophthalmology. - : Elsevier BV. - 0161-6420 .- 1549-4713. ; 120:11, s. 2278-2285
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Ophthalmologic complications after preterm birth are common. Small studies show an association between retinopathy of prematurity and later retinal detachment. There are no population-based studies of preterm birth and risk of retinal detachment, which was the objective of the current investigation.Design: Nationwide Swedish cohort study based on population registries.Participants: Of 3 423 697 subjects born in Sweden, 1 271 725 were born between 1973 and 1986 (i.e., before the national screening program for retinopathy of prematurity started), and 2 151 972 were born between 1987 and 2008. The participants were followed up from 1 year of age until 2009.Methods: Unadjusted and adjusted hazard ratios (HRs) for retinal detachment were calculated using Cox proportional hazards regression.Main Outcome Measures: Incident retinal detachment, as defined by a diagnosis in the Swedish Patient Register (both inpatient and hospital-based outpatient data).Results: During follow-up (median follow-up, 17.4 years), 1749 subjects were diagnosed with retinal detachment. Among the 188 852 subjects born prematurely (i.e., at < 37 weeks of gestation), there were 124 cases of retinal detachment, of which 42 occurred in the 20 470 subjects born before 32 weeks of gestation. Compared with subjects born at term (37-41 weeks), the adjusted HR for retinal detachment after extremely preterm birth (< 28 weeks of gestation) was 19.2 (95% confidence interval [CI], 10.3-35.8) for births between 1973 and 1986 and 8.95 (95% CI, 3.98-20.1) for births between 1987 and 2008. The corresponding HRs in subjects born very prematurely (28-31 weeks) were 4.32 (95% CI, 2.70-6.90) and 2.80 (95% CI, 1.38-5.69), respectively. Moderately preterm birth (32-36 weeks) was not associated with an increased risk of retinal detachment.Conclusions: Birth before 32 weeks of gestation is associated with a substantially increased relative risk of retinal detachment. These findings may have implications for ophthalmologic follow-up of children and adults born very prematurely.
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| 10. |
- Brodd, Katarina Strand, et al.
(författare)
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Development of Smooth Pursuit Eye Movements in very preterm born infants : 3. Association to perinatal risk factors
- 2012
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 101:2, s. 164-171
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the association between perinatal risk factors and neonatal complications and early oculo-motor development in very preterm infants. Methods: Perinatal risk factors were identified, and the potential association with early oculo-motor development was evaluated by measuring smooth pursuit eye movements (SP) at 2 and 4 months' corrected age (CA) in a population of very preterm infants born in Uppsala County 2004-2007 (n = 113). Results: Among the 15 tested factors, eight showed significant association in univariate analysis with lower levels of SP at 4 months' CA, namely administration of prenatal corticosteroids, gestational age, birthweight, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, intraventricular haemorrhage >grade 2, and persistent ductus arteriosus. At 2 months' CA, only retinopathy of prematurity >stage 2 was associated with lower levels of SP. When all factors significant in the univariate tests were included in multiple regressions aimed to assess each factor's independent relation to SP, periventricular leukomalacia was the only significant independent factor. When adding 2-5 of the significant factors using multiple regression analysis, the levels of SP became lower. Conclusion: Perinatal risk factors were associated with lower levels of SP. This could be interpreted as delayed or disturbed development of normal oculomotor ability.
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