| 1. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 7. |
- Porcu, E, et al.
(författare)
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Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3300-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene–trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits.
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| 13. |
- Bakker, Marian K., et al.
(författare)
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Analysis of Mortality among Neonates and Children with Spina Bifida : An International Registry-Based Study, 2001-2012
- 2019
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 33:6, s. 436-448
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Tidskriftsartikel (refereegranskat)abstract
- Background: Medical advancements have resulted in better survival and life expectancy among those with spina bifida, but a significantly increased risk of perinatal and postnatal mortality for individuals with spina bifida remains. Objectives: To examine stillbirth and infant and child mortality among those affected by spina bifida using data from multiple countries. Methods: We conducted an observational study, using data from 24 population- and hospital-based surveillance registries in 18 countries contributing as members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Cases of spina bifida that resulted in livebirths or stillbirths from 20 weeks' gestation or elective termination of pregnancy for fetal anomaly (ETOPFA) were included. Among liveborn spina bifida cases, we calculated mortality at different ages as number of deaths among liveborn cases divided by total number of liveborn cases with spina bifida. As a secondary outcome measure, we estimated the prevalence of spina bifida per 10 000 total births. The 95% confidence interval for the prevalence estimate was estimated using the Poisson approximation of binomial distribution. Results: Between years 2001 and 2012, the overall first-week mortality proportion was 6.9% (95% CI 6.3, 7.7) and was lower in programmes operating in countries with policies that allowed ETOPFA compared with their counterparts (5.9% vs. 8.4%). The majority of first-week mortality occurred on the first day of life. In programmes where information on long-term mortality was available through linkage to administrative databases, survival at 5 years of age was 90%-96% in Europe, and 86%-96% in North America. Conclusions: Our multi-country study showed a high proportion of stillbirth and infant and child deaths among those with spina bifida. Effective folic acid interventions could prevent many cases of spina bifida, thereby preventing associated childhood morbidity and mortality.
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| 18. |
- Rylander, L, et al.
(författare)
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Per- and Polyfluoroalkyl Substances in Early Pregnancy and Risk for Preeclampsia: A Case-Control Study in Southern Sweden
- 2020
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is one of the most common causes of perinatal and maternal morbidity/mortality. One suggested environmental risk factor is exposure to endocrine-disrupting pollutants such as per- and polyfluoroalkyl substances (PFAS). The present case-control study in southern Sweden aims to investigate the hypothesized association between serum concentrations of PFAS in early pregnancy and the risk of developing preeclampsia. The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Maternal serum samples were obtained from a biobank of samples collected in early pregnancy in connection with screening for infections. Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were analyzed using liquid chromatography-tandem-mass-spectrometry (LC/MS/MS). Among primiparous women, there were no differences in PFAS concentrations in early pregnancy between the cases and the controls whereas among multipara women, the cases had significantly higher concentrations of PFNA (median concentrations were 0.44 and 0.38 ng/mL, p = 0.04). When individual PFAS were categorized into quartiles and adjustment for potential confounders was performed, the women in the highest quartiles had no significant increased risks of developing preeclampsia as compared with women in the lowest category. In conclusion, the present study provides limited support for the hypothesized association between PFAS and preeclampsia in a population with relatively low exposure levels.
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| 22. |
- Carlsson, L G, et al.
(författare)
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Efficacy of cumulative doses of salbutamol administered via Turbuhaler or Diskhaler in patients with reversible airway obstruction
- 1998
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 53:7, s. 712-715
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to estimate the relative dose potency of salbutamol inhaled via Turbuhaler and Diskhaler. The 24 adult patients participating had chronic reversible airway obstruction. The study was of a double-blind, double-dummy, crossover, randomized design. Five doses of salbutamol Turbuhaler, 50, 50, 100, 200, and 400 microg, were given on one study day at intervals of 30 min. On another study day, five doses of salbutamol Diskhaler, 200, 200, 400, 800, and 1600 microg, were given with the same interval. The treatment days were separated by a washout period of at least 24 h. The inhalation technique was standardized and supervised. Efficacy variables were recorded before and after each study dose. The primary efficacy variable was forced expiratory volume in 1 s (FEV1). When parallel and linear cumulative dose-response curves were statistically compared on a logarithmic scale, the dose potency of salbutamol Turbuhaler vs salbutamol Diskhaler was 1.99 (95% confidence interval 1.52-2.54). This study indicates that only half the dose of salbutamol is required via Turbuhaler as via Diskhaler for the same bronchodilating effect.
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| 23. |
- Copier, J, et al.
(författare)
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Improving the efficacy of cancer immunotherapy
- 2009
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Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:8, s. 1424-1431
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Tidskriftsartikel (refereegranskat)abstract
- A series of cancer vaccines have been evaluated in clinical trials with encouraging results, but the demonstration of clinical benefit in confirmatory studies has so far proven to be difficult. The development of cancer vaccines is hampered by a range of issues particular to this field of research. On 12th March 2008, the Biotherapy Development Association convened a workshop to discuss issues faced by scientists and clinicians involved in the development of cancer vaccines. This paper is a review of the field, based on discussions held at the BDA workshop, and describes biological barriers encountered in generating effective immune responses to tumours, methodological obstacles encountered in the improvement of immunological monitoring which aims to improve inter-laboratory and inter-trial comparisons, challenges in clinical trial design and problems posed by the lack of specific regulation for cancer vaccines and the impact on their development. Ultimately, a number of general solutions are posed: (1) better patient selection, (2) use of multi-modal treatments that affect several aspects of the immune system at once, (3) a requirement for the development of good biomarkers to stratify patients for selection prior to trial and as surrogates for clinical response and (4) harmonisation of SOPs for immunological monitoring of clinical trials.
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| 24. |
- Farooqi, Aijaz, et al.
(författare)
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One-year survival and outcomes of infants born at 22 and 23 weeks of gestation in Sweden 2004-2007, 2014-2016 and 2017-2019
- 2024
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Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109:1, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden. Design/SettingData on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions. Main outcomeOne-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined. Results977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4). ConclusionIncreased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.
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| 25. |
- Hakansson, L., et al.
(författare)
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Vaccines : A rapidly evolving technology - Are the hurdles being addressed?
- 2007
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Ingår i: European Journal of Cancer, Supplement. - : Elsevier BV. - 1359-6349. ; 5:9, s. 29-32
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination usually works in infectious disease, why not in Cancer? Differences in the potency of microbial and cancer antigens, poor initiation of an immune response due to inadequate expression of tumour associated antigens, weak antigens or tolerance induction and local immune suppression were considered. There is a big difference between a therapeutic and a prophylactic vaccine. The opinion of the expert group was that an improved therapeutic efficacy can hardly be expected by further variation of types of vaccines, schedules, routes of administration and adjuvants alone. A major hurdle for developing therapeutic cancer vaccines is the need to effectively monitor the immune response and to be able to use this in an adaptive trial approach. End-points of assessment should be different from standard treatments as complete response or partial responses are usually low, unless combined with other therapies. In order to focus resources to overcome the hurdles of enhancing the therapeutic efficacy of cancer vaccines the Cancer Vaccine Clinical Trial Working Group, representing academia and the pharmaceutical and biotechnology industries has in a consensus process defined 'A clinical development paradigm for cancer vaccines and related biologics'. © 2007 Elsevier Ltd. All rights reserved.
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| 26. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 29. |
- Kallen, Kristina, et al.
(författare)
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Epilepsy surgery in the Nordic countries
- 2008
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Ingår i: Textbook of Epilepsy Surgery. - 1841845760 - 9781841845760 ; , s. 77-83
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 30. |
- Källén, Karin, et al.
(författare)
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Ophthalmologic Outcome of Extremely Preterm Infants at 6.5 Years of Age Extremely Preterm Infants in Sweden Study (EXPRESS)
- 2016
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Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 134:5, s. 555-562
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE This follow-up study of extremely preterm (EPT) children (<27 weeks' gestational age [GA] at birth) revealed major eye and visual problems in 37.9%(147 of 388) of all EPT infants and in 55.4%(67 of 121) of the most immature subgroups at 6.5 years of age. These major eye and visual problems were strongly associated with treatment-requiring retinopathy of prematurity (ROP). OBJECTIVES To investigate the ophthalmologic outcome of a national cohort of EPT children at 6.5 years of age and to evaluate the impact of prematurity and ROP. DESIGN, SETTING, AND PARTICIPANTS All surviving EPT children born in Sweden between April 1, 2004, and March 31, 2007, were included and compared with a matched term control group, as part of a prospective national follow-up study. MAIN OUTCOMES AND MEASURES Visual acuity, refraction in cycloplegia, and manifest strabismus were evaluated and compared with GA at birth and with treatment-requiring ROP. RESULTS The study cohort comprised 486 participants. The mean (SD) GA of the children who were included was 25 (1) weeks, and 45.7%(222 of 486) were female. At a median age of 6.6 years, 89.3%(434 of 486) of eligible EPT children were assessed and compared with 300 control group children. In the EPT group, 2.1%(9 of 434) were blind, 4.8%(21 of 434) were visually impaired according to the World Health Organization criteria, and 8.8% (38 of 434) were visually impaired according to the study criteria. Strabismus was found in 17.4% (68 of 390) and refractive errors in 29.7%(115 of 387) of the EPT children compared with 0% (0 of 299) and 5.9% (17 of 289), respectively, of the control children (P<.001). Altogether at 6.5 years of age, 37.9%(147 of 388) of the EPT children had some ophthalmologic abnormality compared with 6.2%(18 of 290) of the matched control group (95% CI of the difference, 26.1%-37.2%). When treatment-requiring ROP was adjusted for, no significant association between GA and visual impairment could be detected. For refractive errors, the association with GA remained after adjustment for treatment-requiring ROP (odds ratio, 0.72; 95% CI, 0.58-0.91 for each 1-week increment). CONCLUSIONS AND RELEVANCE In a Swedish national cohort of EPT children at 6.5 years of age, major eye and visual problems were frequently found. Treatment-requiring ROP was a stronger impact factor than GA on visual impairment and strabismus, but not on refractive errors, as a whole. In modern neonatal intensive care settings, ophthalmologic problems continue to account for a high proportion of long-term sequelae of prematurity.
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| 32. |
- Löfdahl, Claes-Göran, et al.
(författare)
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Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction
- 1997
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 10:11, s. 2474-2478
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Tidskriftsartikel (refereegranskat)abstract
- Two studies are presented, with the aim of establishing the dose potency ratio for salbutamol given via Turbuhaler and via a pressurized metered-dose inhaler (pMDI). Both studies were of a double-blind, randomized design. Outpatients with mild-to-moderate chronic reversible airway obstruction were given single doses of salbutamol administered via Turbuhaler and via pMDI. Efficacy and safety variables were measured before and during 6 h after each dose. The first study was a four-way crossover study including 12 patients. The salbutamol doses given were: 50, 100 and 2x100 microg via Turbuhaler and 2x100 microg via pMDI (Ventolin). The study showed that 2x100 microg of salbutamol inhaled via Turbuhaler is more potent than 2x100 microg salbutamol inhaled via a pMDI, and that 100 microg salbutamol via Turbuhaler is at least as potent as 2x100 microg salbutamol inhaled via a pMDI. The second study including 50 patients was a placebo-controlled five-way crossover, study. Two doses of salbutamol via Turbuhaler, 50 and 2x100 microg, and via pMDI, 100 and 2x200 microg, were given. There was a dose-dependent response in forced expiratory volume in one second (FEV1) for both inhalers. Adjusted for differences in baseline FEV1 values, the estimated relative dose potency for Turbuhaler versus pMDI was 1.98:1 (95% confidence interval 12-3.2). These studies showed that the same bronchodilating effect can be achieved when half the dose of salbutamol given via a conventional pressurized metered-dose inhaler is given via Turbuhaler.
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| 34. |
- Morken, Nils-Halvdan, 1969, et al.
(författare)
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Reference population for international comparisons and time trend surveillance of preterm delivery proportions in three countries
- 2008
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Ingår i: BMC Womens Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: International comparison and time trend surveillance of preterm delivery rates is complex. New techniques that could facilitate interpretation of such rates are needed. METHODS: We studied all live births and stillbirths (>or= 28 weeks gestation) registered in the medical birth registers in Sweden, Denmark and Norway from 1995 through 2004. Gestational age was determined by best estimate. A reference population of pregnant women was designed using the following criteria: 1) maternal age 20-35, 2) primiparity, 3) spontaneously conceived pregnancy, 4) singleton pregnancy and 5) mother born in the respective country. National preterm delivery rate, preterm delivery rate in the reference population and rate of spontaneous preterm delivery in the reference population were calculated for each country. RESULTS: The total national preterm delivery rate (< 37 completed gestational weeks), increased in both Denmark (5.3% to 6.1%, p < 0.001) and Norway (6.0% to 6.4%, p = 0.006), but remained unchanged in Sweden, during 1995-2004. In Denmark, the preterm delivery rate in the reference population (5.3% to 6.3%, p < 0.001) and the spontaneous preterm delivery rate in the reference population (4.4% to 6.8%, p < 0.001) increased significantly. No similar increase was evident in Norway. In Sweden, rates in the reference population remained stable. CONCLUSION: Reference populations can facilitate overview and thereby explanations for changing preterm delivery rates. The model also permits comparisons over time. This model may in its simplicity prove to be a valuable supplement to assessments of national preterm delivery rates for public health surveillance.
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