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  • Arat, Arzu, et al. (författare)
  • Organisation of preventive child health services : Key to socio-economic equity in vaccine uptake?
  • 2020
  • Ingår i: ; 48:5, s. 491-494
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Measles has made a comeback in Western Europe, with more cases being reported each year. One factor behind this development is low vaccination coverage in socially disadvantaged segments of the population in many countries. This study investigates whether socioeconomic patterns of uptake of the measles, mumps and rubella (MMR) vaccine in the Nordic countries differ by national organisation of preventive health services for children. METHODS: MMR vaccine uptake before the age of two years was analysed in register data from Denmark, Finland, Iceland and Sweden, linked to family indicators of socio-economic status (SES) from national registers. RESULTS: Denmark, a country where child vaccinations are administered by general practitioners, presented the lowest overall coverage of MMR at 83%. It also had the greatest difference between subpopulations of low and high SES at 14 percentage points. Finland, Iceland and Sweden, countries where preschool children are vaccinated in 'well-baby' clinics, had a higher overall coverage at 91-94%, with a more equal distribution between SES groups at 1-4 percentage points. CONCLUSIONS: This study suggests that the organisation of preventive health care in special units, 'well-baby' clinics, facilitates vaccine uptake among children with low SES in a Nordic welfare context.
  • Oskarsson, Trausti, et al. (författare)
  • Relapsed childhood acute lymphoblastic leukemia in the Nordic countries : prognostic factors, treatment and outcome
  • 2016
  • Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 101:1, s. 68-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5 +/- 3.4%, but 44.7 +/- 3.2% (P<0.001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis. The outcome for early combined pre-B relapses was unexpectedly poor (5-year overall survival 38.0 +/- 10.6%), which supports the notion that these patients need further risk adjustment. Although survival outcomes have improved over time, the development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia.
  • Albertsson-Wikland, Kerstin, et al. (författare)
  • Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
  • 2008
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH). OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls. DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden. INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated. SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population. MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS. RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations. CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls. 
  • Albertsson-Wikland, Kerstin, et al. (författare)
  • Growth hormone dose-dependent pubertal growth : a randomized trial in short children with low growth hormone secretion
  • 2014
  • Ingår i: Hormone Research in Paediatrics. - : Karger. - 1663-2818 .- 1663-2826. ; 82:3, s. 158-170
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i. e. idiopathic isolated GH deficiency.Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH(33) mu g/kg/day for >= 1 year. They were randomized to receive 67 mu g/kg/day (GH(67)) given as one (GH(67x1); n = 35) or two daily injections (GH(33x2); n = 36), or to remain on a single 33 mu g/kg/day dose (GH(33x1); n = 40). Growth was assessed as height SDS gain for prepubertal, pubertal and total periods, as well as AH SDS versus the population and the midparental height.Results: Pubertal height SDS gain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33x1), 0.41, p < 0.05). AH(SDS) was greater on GH(67) (GH(67x1), -0.84; GH(33x2), -0.83) than GH(33) (-1.25, p < 0.05), and height SDS gain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height SDS.Conclusion: Pubertal height SDS gain and AH SDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once-and twice-daily GH(67) regimens. (C) 2014 S. Karger AG, Basel.
  • Nordlund, Jessica, et al. (författare)
  • Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia
  • 2013
  • Ingår i: ; 14:9, s. Article number: r105-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic background, drug resistance and relapse in ALL is poorly understood. Results: We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. This survey uncovered four characteristic methylation signatures. First, compared with control blood cells, the methylomes of ALL cells shared 9,406 predominantly hypermethylated CpG sites, independent of cytogenetic background. Second, each cytogenetic subtype of ALL displayed a unique set of hyper- and hypomethylated CpG sites. The CpG sites that constituted these two signatures differed in their functional genomic enrichment to regions with marks of active or repressed chromatin. Third, we identified subtype-specific differential methylation in promoter and enhancer regions that were strongly correlated with gene expression. Fourth, a set of 6,612 CpG sites was predominantly hypermethylated in ALL cells at relapse, compared with matched samples at diagnosis. Analysis of relapse-free survival identified CpG sites with subtype-specific differential methylation that divided the patients into different risk groups, depending on their methylation status. Conclusions: Our results suggest an important biological role for DNA methylation in the differences between ALL subtypes and in their clinical outcome after treatment.
  • Oskarsson, Trausti, et al. (författare)
  • Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia
  • 2018
  • Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 65:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival.Procedure: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials.Results: Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment-related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment-related mortality were as follows: high-risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3-3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3-9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17-9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment-related causes.Conclusions: Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL.
  • Scott, Robert A., et al. (författare)
  • No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels
  • 2012
  • Ingår i: Diabetes. - Alexandria, VA : American Diabetes Association Inc.. - 1939-327X .- 0012-1797. ; 61:5, s. 1291-1296
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) X BMI and SNP x physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (beta = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 X 10(-6)). All SNPs were associated with 2-h glucose (beta = 0.06-0.12 mmol/allele, P <= 1.53 X 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P >= 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions. Diabetes 61:1291-1296, 2012
  • Sebhatu, Abiel, et al. (författare)
  • Explaining the homogeneous diffusion of COVID-19 nonpharmaceutical interventions across heterogeneous countries
  • 2020
  • Ingår i: ; 117:35, s. 21201-21208
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyze the adoption of nonpharmaceutical interventions in the Organisation for Economic Co-operation and Development (OECD) countries during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. Given the complexity associated with pandemic decisions, governments are faced with the dilemma of how to act quickly when their core decision-making processes are based on deliberations balancing political considerations. Our findings show that, in times of severe crisis, governments follow the lead of others and base their decisions on what other countries do. Governments in countries with a stronger democratic structure are slower to react in the face of the pandemic but are more sensitive to the influence of other countries. We provide insights for research on international policy diffusion and research on the political consequences of the COVID-19 pandemic.
  • Chaplin, John Eric, et al. (författare)
  • Improvements in behaviour and self-esteem following growth hormone treatment in short prepubertal children
  • 2011
  • Ingår i: Hormone research in paediatrics. - 1663-2826 .- 1663-2818. ; 75:4, s. 291-303
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: To evaluate effects of growth hormone (GH) treatment on behaviour and psychosocial characteristics in short-stature children. Methods: 99 referred prepubertal non-familiar short-stature children (32 GH deficiency; 67 idiopathic short stature) aged 3-11 years, randomized to fixed or individual GH doses and their parents completed questionnaires (Child Behaviour Checklist, Birleson Depression Self-Report Scale, Abbreviated Parent-Teacher Questionnaire, I Think I Am, Well-Being Visual-Analogue Scales for Short-Stature Children) at baseline (BL) and after 3, 12, and 24 months. Results: At BL, children showed higher levels of internalizing behaviour (p < 0.001), lower levels of externalizing behaviour (p < 0.006) and self-esteem (p < 0.001) compared to reference values. During GH treatment, behavioural measures (p < 0.001) and depression (p < 0.01) changed towards the mean of the population within the first 3 months and remained improved to 24 months. Self-esteem improved at all time points (p < 0.001), and in all subgroups, as did well-being dimensions stability and mood (p < 0.05). Multiple regression analysis showed that greater improvements were related to lower BL value, height gain, higher maximal GH value, being older, and being male. Conclusion: On GH treatment, prepubertal short children significantly improved on behavioural, depression, and psychosocial evaluations over a 2-year period of GH treatment. Most change occurred within the first 3 months, which highlights this short period as important not only for growth and metabolic changes but also for behaviour and psychosocial improvements following GH treatment.
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