Publications by authors named "Pernille Mathiesen"

10 Publications

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[Greater vigilance in medication for children and adolescent is warranted in Denmark].

Ugeskr Laeger 2020 Nov;182(45)

Only 30% of medication used for children and adolescents and 10% of the medication used for neonates has been evaluated for use in these populations. Infants and children differ from adults regarding pharmacodynamic and -kinetics, but they also differ from each other due to e.g. age, weight, and body composition, as we argue in this review. There is only limited knowledge within this area leading to the use of off-label, extemporaneous and unlicensed medication. Greater national vigilance in medication for children and adolescent is warranted to secure better and safer medicine for newborns, infants, children and adolescents.
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November 2020

Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups.

Ann Rheum Dis 2019 07 28;78(7):996-1002. Epub 2019 May 28.

Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.

Objectives: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.

Methods: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups.

Results: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10 and HLA-DRB1*03:01, p=3.25×10), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10) and position 9 of HLA-B (p=7.03×10). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies.

Conclusions: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.
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http://dx.doi.org/10.1136/annrheumdis-2019-215046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585280PMC
July 2019

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research.

Ann Rheum Dis 2018 02 30;77(2):241-250. Epub 2017 Oct 30.

Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.

Objectives: This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres.

Methods: A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation.

Results: A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter.

Conclusions: Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases.
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http://dx.doi.org/10.1136/annrheumdis-2017-212141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816738PMC
February 2018

The Child Health System in Denmark: Current Problems and Successes.

J Pediatr 2016 10 22;177S:S60-S62. Epub 2016 Sep 22.

Department of Pediatrics, Regional Hospital Viborg, Viborg, and Center of Health Educations Education, Aarhus, Denmark.

In Denmark, child primary care is taken care of by general practitioners who have 6 months of pediatric training as part of their specialty training and, therefore, are qualified to work as gatekeepers for the secondary health care at the hospitals. As new, more expensive, drugs are increasingly prescribed, corresponding expenses pose serious threats to the economy at 18 pediatric departments. We will highlight the new developments in pediatric education: skills training and training of clinical reasoning.
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http://dx.doi.org/10.1016/j.jpeds.2016.04.042DOI Listing
October 2016

Proposal for a Candidate Core Set of Fitness and Strength Tests for Patients with Childhood or Adult Idiopathic Inflammatory Myopathies.

J Rheumatol 2016 Jan 15;43(1):169-76. Epub 2015 Nov 15.

Objective: Currently there are no evidence-based recommendations regarding fitness and strength tests for patients with childhood or adult idiopathic inflammatory myopathies (IIM). This hinders clinicians and researchers in choosing the appropriate fitness- or muscle strength-related outcome measures for these patients. Through a Delphi survey, we aimed to identify a candidate core set of fitness and strength tests for children and adults with IIM.

Methods: Fifteen experts participated in a Delphi survey that consisted of 5 stages to achieve a consensus. Using an extensive search of published literature and through the work of experts, a candidate core set based on expert opinion and clinimetrics properties was developed. Members of the International Myositis Assessment and Clinical Studies Group were invited to review this candidate core set during the final stage, which led to a final candidate core set.

Results: A core set of fitness- and strength-related outcome measures was identified for children and adults with IIM. For both children and adults, different tests were identified and selected for maximal aerobic fitness, submaximal aerobic fitness, anaerobic fitness, muscle strength tests, and muscle function tests.

Conclusion: The core set of fitness- and strength-related outcome measures provided by this expert consensus process will assist practitioners and researchers in deciding which tests to use in patients with IIM. This will improve the uniformity of fitness and strength tests across studies, thereby facilitating the comparison of study results and therapeutic exercise program outcomes among patients with IIM.
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http://dx.doi.org/10.3899/jrheum.150270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698199PMC
January 2016

Dense genotyping of immune-related loci in idiopathic inflammatory myopathies confirms HLA alleles as the strongest genetic risk factor and suggests different genetic background for major clinical subgroups.

Ann Rheum Dis 2016 Aug 11;75(8):1558-66. Epub 2015 Sep 11.

Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.

Objectives: The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and extramuscular manifestations such as skin rashes and interstitial lung disease. We genotyped 2566 IIM cases of Caucasian descent using the Immunochip; a custom array covering 186 established autoimmune susceptibility loci. The cohort was predominantly comprised of patients with dermatomyositis (DM, n=879), juvenile DM (JDM, n=481), polymyositis (PM, n=931) and inclusion body myositis (n=252) collected from 14 countries through the Myositis Genetics Consortium.

Results: The human leucocyte antigen (HLA) and PTPN22 regions reached genome-wide significance (p<5×10(-8)). Nine regions were associated at a significance level of p<2.25×10(-5), including UBE2L3, CD28 and TRAF6, with evidence of independent effects within STAT4. Analysis of clinical subgroups revealed distinct differences between PM, and DM and JDM. PTPN22 was associated at genome-wide significance with PM, but not DM and JDM, suggesting this effect is driven by PM. Additional suggestive associations including IL18R1 and RGS1 in PM and GSDMB in DM were identified. HLA imputation confirmed that alleles HLA-DRB1*03:01 and HLA-B*08:01 of the 8.1 ancestral haplotype (8.1AH) are most strongly associated with IIM, and provides evidence that amino acids within the HLA, such as HLA-DQB1 position 57 in DM, may explain part of the risk in this locus. Associations with alleles outside the 8.1AH reveal differences between PM, DM and JDM.

Conclusions: This work represents the largest IIM genetic study to date, reveals new insights into the genetic architecture of these rare diseases and suggests different predominating pathophysiology in different clinical subgroups.
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http://dx.doi.org/10.1136/annrheumdis-2015-208119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300750PMC
August 2016

Pulmonary function and autoantibodies in a long-term follow-up of juvenile dermatomyositis patients.

Rheumatology (Oxford) 2014 Apr 5;53(4):644-9. Epub 2013 Dec 5.

Paediatric Department, Holbaek University Hospital, DK-4300 Holbaek, Denmark.

Objectives: Pulmonary disease is a rare complication in JDM, described in only a few studies. This long-term follow-up study aimed to (i) describe pulmonary involvement in a national cohort of JDM patients estimated by conventional spirometry, (ii) compare pulmonary impairment with overall JDM outcome, and (iii) identify possible associations between pulmonary impairment and myositis-specific autoantibodies (MSAs).

Methods: Fifty-one JDM patients performed conventional spirometry in a cross-sectional follow-up study. The scores of the Myositis Damage Index (MDI), Myositis Damage by visual analogue scale (MYODAM-VAS) and physician's global damage assessment were used to estimate JDM outcome. ANAs, MSAs and myositis-associated autoantibodies were analysed in all patients.

Results: Forty-two patients (82%) (mean follow-up time 14.3 years) had normal lung function. Four patients (8%) were diagnosed with JDM-related restrictive interstitial lung disease. No patients reported pulmonary symptoms. Patients with restrictive pulmonary function had increased long-term damage estimated by MDI (P = 0.008), MYODAM-VAS (P = 0.04), global assessment (P = 0.03) and number of organ systems involved (P = 0.009). We found significant correlation between the restrictive pulmonary function test and damage by the MDI (r = 0.43, P = 0.003), MYODAM-VAS (r = 0.44, P = 0.002), and global damage assessment (r = 0.43, P = 0.003). No association was found between the restrictive pulmonary function test and autoantibodies.

Conclusion: In a long-term follow-up study of JDM patients, the majority of patients demonstrated normal lung function. However, restrictive pulmonary impairment was identified in 8% of patients, indicating a need for repetitive pulmonary follow-up in JDM patients. Restrictive pulmonary involvement was associated with increased long-term JDM damage.
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http://dx.doi.org/10.1093/rheumatology/ket380DOI Listing
April 2014

Aerobic fitness after JDM--a long-term follow-up study.

Rheumatology (Oxford) 2013 Feb 22;52(2):287-95. Epub 2012 Sep 22.

Paediatric Department, Holbaek University Hospital, Holbaek, DK-4300 Denmark.

Objectives: It has previously been shown that patients with active JDM have decreased aerobic fitness; however, it is not known whether these patients regain their physical fitness after recovery. The objective of this study was to investigate the long-term outcome of aerobic fitness in patients with JDM. We hypothesized that fitness (VO(2max)) is reduced compared with healthy controls in the years after active JDM.

Methods: A maximal exercise test was performed using a cycle ergometer. Results were compared with those of sex- and age-matched healthy controls.

Results: A total of 36 patients with JDM in remission were included, 2-36 years after disease onset. Twelve patients (33%) had normal VO(2max) and 24 patients (67%) had decreased VO(2max). Mean VO(2max) was higher in the healthy controls vs patients (P < 0.001, 95% CI -10.7, -4.4). A significant difference between patients with JDM and controls was observed for women (P < 0.001), men (P = 0.04), children < 18 years (P = 0.002) and adults > 18 years (P = 0.01). The decreased VO(2max) was independent of the duration of remission, but it was associated with the duration of active disease. By linear regression, it was revealed that for every year of active disease, VO(2max) was reduced by 0.85 ml/min/kg on average (P < 0.001).

Conclusion: This long-term follow-up study demonstrates that patients who have had JDM have persistently impaired fitness. This impairment is directly related to the duration of active disease.
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http://dx.doi.org/10.1093/rheumatology/kes232DOI Listing
February 2013

[Congenital sternal cleft].

Ugeskr Laeger 2007 Mar;169(11):1022-4

Storstrømmens Sygehus Nykøbing Falster, Paediatrisk og Radiologisk Afdeling.

We describe two children with congenital sternal cleft. One child had a complete sternal cleft that was not operated upon, and at the age of 11 years the boy was still free of any symptoms. The other child had a superior partial sternal cleft that needed operative closure in the neonatal period. X-ray, CT scan of the chest and echocardiography are recommended for primary evaluation. Indications for surgical intervention are protection of the mediastinal structures, improvement of respiratory dynamics and cosmetic considerations.
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March 2007

[Hypernatremia and neurological complications in rotavirus gastroenteritis].

Ugeskr Laeger 2005 Jan;167(4):409-10

Amtssygehuset i Glostrup, Paediatrisk Afdeling.

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January 2005