[Show abstract][Hide abstract] ABSTRACT: To determine whether clinical, laboratory or Magnetic Resonance Imaging (MRI) measures differentiate Juvenile Idiopathic Arthritis (JIA) from other forms of active childhood arthritis.
We prospectively collected data of 80 treatment-naïve patients clinically suspected of JIA with active non-infectious arthritis of (at least) one knee for <12 months duration. Upon presentation patients underwent clinical and laboratory assessments and contrast-enhanced MRI. MRI was not used as a diagnostic criterion.
Forty-four (55 %) patients were clinically diagnosed with JIA, whereas in 36 (45 %) patients the diagnosis of JIA was discarded on clinical or laboratory findings. MRI-based synovitis was present in 27 (61.4 %) JIA patients and in 7 (19.4 %) non-JIA patients (P < 0.001). Five factors (male gender, physician's global assessment of overall disease activity, joints with limited range of motion, HLA-B27, MRI-based synovitis) were associated with the onset of JIA. In multivariate analysis MRI-based synovitis proved to be independently associated with JIA (OR 6.58, 95 % CI 2.36-18.33). In patients with MRI-based synovitis, the RR of having JIA was 3.16 (95 % CI 1.6-6.4).
The presence of MRI-based synovitis is associated with the clinical onset of JIA. Physical examination could be supported by MRI, particularly to contribute in the early differentiation of different forms of non-infectious childhood arthritis.
• Juvenile Idiopathic Arthritis (JIA) is a diagnosis of exclusion. • Differentiating JIA and other forms of childhood arthritis can be difficult. • MRI-techniques have substantially improved evaluation of joint abnormalities in JIA patients. • MRI-based synovitis is significantly associated with the clinical onset of JIA. • MRI could support physical examination in the early differentiation of childhood arthritis.
European Radiology 05/2015; DOI:10.1007/s00330-015-3752-x · 4.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Depression is a common disorder in pregnancy and associated with adverse effects for both mother and neonate. Pharmacological treatment and prevention options include mirtazapine. In a series of 56 cases, we investigated neonatal outcome after intrauterine exposure to mirtazapine and exposure through lactation in the first days postpartum.No increase in any neonatal complication was observed. None of the infants exposed to mirtazapine in the first trimester were born with a major malformation. Of the 54 infants exposed to mirtazapine in the third trimester, 14 were diagnosed with poor neonatal adaptation syndrome (PNAS). This incidence (25.9%) is similar to the incidence of PNAS after intrauterine exposure to other antidepressants. The incidence of PNAS after exposure to mirtazapine was significantly diminished in children who were partially or fully breastfed (18.6% versus 54.5%, P = 0.024).
Journal of Clinical Psychopharmacology 02/2015; DOI:10.1097/JCP.0000000000000279 · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimInfants exposed to antidepressants in utero are at risk of developing poor neonatal adaptation (PNA). This study identified risk factors for PNA.Methods
In this cohort study, data on mothers and infants admitted to the maternity ward of a generalhospital between 2007 and 2012 were analysed. All infants were exposed to an antidepressantduring the last trimester of fetal life. The main outcome measure was PNA, defined as at least one Finnegan scores of four or more during admission. Risk factors analysed for their possible association with PNA included type of feeding, type and dosage of antidepressant, prematurity and maternal smoking, anxiety and depression.ResultsWe included 247 infants in the study and 157 (64%) developed PNA. Formula feeding was associated with an increased risk of PNA compared to breastfeeding or mixed feeding (OR3.16 95%CI 1.40-7.13 p0.003). Selective serotonin reuptake inhibitors (SSRIs) were associated with an increased risk of PNA compared to serotonin and norepinephrine reuptake inhibitors (OR2.52 95%CI 1.07-5.95 p0.04). Dosage did not influence the risk of PNA (OR 1.50 95%CI 0.89-2.52 p0.13).Conclusion
Formula feeding and exposure to SSRIs were associated with development of PNA, but dosage was not.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective The Finnegan scoring list (FSL) is widely used to screen for Poor Neonatal Adaptation in infants exposed to antidepressants in utero. However, the large number of FSL-items and differential weighing of each item is time consuming. The aim of this study was to shorten and simplify the FSL yet preserving its clinimetric properties. Methods This observational study examined infants exposed to an antidepressant during pregnancy admitted for at least 72 hours on a maternity ward. Trained nurses completed the FSL three times daily. Items for the adapted FSL were selected through forward analysis whereby the number of selected items was based on the Area Under the Curve (AUC). Internal validity was assessed by cross-validation. Results 183 infants met the inclusion criteria. By forward analysis 8 equally-weighed items resulted in an AUC of 0.91. In cross-validation, the mean AUC was 0.89 for 8 items. This adapted FSL had a sensitivity of 97.7% and specificity of 37.0% and a sensitivity of 41.9% and specificity of 86.2% regarding a cut off of respectively 1 and 2. Conclusions An adapted FSL with 8 equally-weighed items has acceptable clinimetric properties and can serve as an easy to apply screening tool in infants exposed to antidepressants during pregnancy.
Journal of Maternal-Fetal and Neonatal Medicine 10/2014; DOI:10.3109/14767058.2014.977247 · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: To determine the prevalence of hand- and wrist-related symptoms and impairments, with resulting activity limitations and participation restrictions in children being treated for juvenile idiopathic arthritis. Design and patients: Cohort study of children, diagnosed in our hospitals between 2003 and 2008 with juvenile idiopathic arthritis, who received standard treatment with regular follow-ups in the same institutions. Patients were asked about hand and wrist symptoms, and underwent a standardized physical examination. For activity limitations, they were asked to complete the Dutch version of the Childhood Health Assessment Questionnaire (CHAQ). Concerning participation restrictions, children were asked about any hand- and/or wrist-related difficulties during daily activities. Results: Of all 152 eligible patients, 121 (80%) participated in the study; 34 boys and 87 girls, mean age 13.7 years (standard deviation (SD) 4.2), mean disease duration 2.6 years (SD 1.4), mean Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71) score 8 (SD 8), indicating low disease activity. Of these 121, 84 (69%) had at least 1 symptom and 40% had at least 1 impairment. The median CHAQ-total score was 0.5 (mean 0.75 (SD 0.77)), indicating mild-to-moderate activity limitations; and 54% reported having hand- and/or wrist-related problems at school. Conclusion: Despite low disease activity, many children appeared to have hand- and/or wrist-related symptoms and impairments, with resulting moderate to severe levels of activity limitations and participation restrictions at school.
Journal of Rehabilitation Medicine 09/2014; 46(10):991-6. DOI:10.2340/16501977-1879 · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE. The aim of this study in clinically active juvenile idiopathic arthritis (JIA) was to assess the frequency and distribution pattern of synovitis as hallmark of disease and additional soft-tissue and bony abnormalities on MRI in the knee and wrist as two target joints. MATERIALS AND METHODS. MRI datasets of 153 clinically active JIA patients (110 with knee and 43 with wrist involvement) were evaluated independently by two readers for the presence of literature-based imaging features: "synovial hypertrophy," "bone marrow changes," "bone erosions," "tenosynovitis" (only in the wrist), and "cartilage lesions" (only in the knee) in accordance with validated definitions and scoring locations. RESULTS. Synovial hypertrophy was most frequently observed-both in the knee and in the wrist (61.8-65.1% of cases). For the knee, the most frequently involved locations were the cruciate ligaments (46/183 locations [25.1%] affected with synovial hypertrophy) and medial patella (18/62 locations [29.0%] with bone marrow changes). Cartilage lesions and bone erosions were rare (5.5-7.3% of cases). For the wrist, most frequently involved were the radiocarpal joint (21/64 locations [32.8%] with synovial hypertrophy), lunate (7/46 locations [15.2%] with bone marrow changes), and capitate or triquetrum (6/28 locations [21.4%] with bone erosions). Tenosynovitis was a common wrist-specific feature (46.5% of cases). MRI showed no abnormalities in a subgroup of patients with clinically active knee (23.6%) and wrist (16.3%) involvement. CONCLUSION. The distribution pattern of MRI abnormalities in the knee and wrist of active JIA patients provides a practical tool to detect a signature of JIA disease activity in target joints.
American Journal of Roentgenology 05/2014; 202(5):W439-46. DOI:10.2214/AJR.13.11314 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare DCE-MRI parameters and the relative number of time-intensity curve (TIC) shapes as derived from pixel-by-pixel DCE-MRI TIC shape analysis between knees of clinically active and inactive juvenile idiopathic arthritis (JIA) patients.
DCE-MRI data sets were prospectively obtained. Patients were classified into two clinical groups: active disease (n = 43) and inactive disease (n = 34). Parametric maps, showing seven different TIC shape types, were created per slice. Statistical measures of different TIC shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV), volume transfer constant (K (trans)), extravascular space fractional volume (V e) and reverse volume transfer constant (k ep) of each voxel were calculated in a three-dimensional volume-of-interest of the synovial membrane.
Imaging findings from 77 JIA patients were analysed. Significantly higher numbers of TIC shape 4 (P = 0.008), median ME (P = 0.015), MIS (P = 0.001) and iAUC (P = 0.002) were observed in clinically active compared with inactive patients. TIC shape 5 showed higher presence in the clinically inactive patients (P = 0.036).
The pixel-by-pixel DCE-MRI TIC shape analysis method proved capable of differentiating clinically active from inactive JIA patients by the difference in the number of TIC shapes, as well as the descriptive parameters ME, MIS and iAUC.
• The pixel-by-pixel TIC shape method differentiates clinically active and inactive JIA patients • Significantly higher numbers of TIC shape 4 were observed in clinically active patients • DCE-MRI parameters ME, MIS and iAUC differ between active and inactive patients • The pixel-by-pixel analysis method allows direct visualization of the heterogeneously distributed disease • The DCE-MRI TIC shape method may serve as a quantitative outcome measure.
European Radiology 04/2014; 24(7). DOI:10.1007/s00330-014-3168-z · 4.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biological agents in 1999.
To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA.
The Arthritis and Biologics in Children register (multicentre prospective observational study) aimed to include all consecutive patients with JIA in the Netherlands who had started biological agents since 1999. Patients were divided according to year of introduction of first biological agent. Patient characteristics at introduction of the first biological agent and its effectiveness were analysed over 12 years.
335 patients with non-systemic JIA and 86 patients with systemic JIA started a biological agent between 1999 and 2010. Etanercept remained the most often prescribed biological agent for non-systemic JIA; anakinra became first choice for systemic JIA. The use of systemic glucocorticoids and synthetic disease-modifying antirheumatic drugs before biological agents decreased. During these 12 years of observation, biological agents were prescribed earlier in the disease course and to patients with lower baseline JADAS (Juvenile Arthritis Disease Activity Score) disease activity. All baseline disease activity parameters were lowered in patients with non-systemic JIA. In systemic JIA, prescription patterns changed towards very early introduction of biological agents (median 0.4 years of disease duration) in patients with a low number of joints with active arthritis and high erythrocyte sedimentation rates. These changes for both systemic and non-systemic JIA resulted in more patients with inactive disease after 3 and 15 months of treatment.
Biological agents are increasingly prescribed, earlier in the disease and in patients with JIA with lower disease activity. These changes are accompanied by better short-term disease outcomes.
Annals of the rheumatic diseases 03/2014; DOI:10.1136/annrheumdis-2013-204641 · 9.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether clinical disease activity findings during 1-year followup of patients with juvenile idiopathic arthritis (JIA) is associated with changes of magnetic resonance imaging (MRI)-based disease activity scores.
Patients with JIA who had active knee involvement were studied using an open-bore MRI. After followup of a median of 1.3 years, patients were re-evaluated and classified as improved or unimproved according to the American College of Rheumatology Pediatric-50 (ACR-Ped50) criteria. Baseline and followup MRI features were scored by 2 readers using the Juvenile Arthritis MRI Scoring (JAMRIS) system, comprising validated scores for synovial hypertrophy, bone marrow changes, cartilage lesions, and bone erosions.
Data of 40 patients were analyzed (62.5% female, mean age 12.2 yrs). After followup, 27 patients (67.5%) were classified as clinically improved, whereas 13 patients (32.5%) showed no clinical improvement. The clinically improved patients showed a significant reduction in synovial hypertrophy scores during followup (p < 0.001), with substantial effects (standardized response mean -0.70). No such changes were observed for any of the other MRI features. Significant differences were detected regarding a change in synovial hypertrophy scores comparing clinically improved and unimproved patients (p = 0.004), without statistically significant differences for changes in scores for bone marrow changes (p = 0.079), cartilage lesions (p = 0.165), and bone erosions (p = 0.078).
This is one of the first studies to provide evidence for MRI-based improvement upon followup in JIA patients with knee involvement. There is a strong association with clinical improvement according to the ACR-Ped50 criteria and changes in MRI-based synovial hypertrophy scores, supporting the role of MRI as a responsive outcome measure to evaluate disease activity with antiinflammatory treatment strategies.
The Journal of Rheumatology 12/2013; 41(1). DOI:10.3899/jrheum.130235 · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the value of magnetic resonance imaging (MRI) in discriminating between active and inactive juvenile idiopathic arthritis (JIA) patients and to compare physical examination outcomes with MRI outcomes in the assessment of disease status in JIA patients.
Consecutive JIA patients with knee involvement were prospectively studied using an open-bore MRI. Imaging findings from 146 JIA patients were analysed (59.6 % female; mean age, 12.9 years). Patients were classified as clinically active or inactive. MRI features were evaluated using the JAMRIS system, comprising validated scores for synovial hypertrophy, bone marrow oedema, cartilage lesions and bone erosions.
Inter-reader reliability was good for all MRI features (intra-class correlation coefficient [ICC] = 0.87-0.94). No differences were found between the two groups regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions. Synovial hypertrophy scores differed significantly between groups (P = 0.016). Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9 %) with clinically inactive disease. Of JIA patients considered clinically active, 48.6 % showed no signs of MRI-based synovitis.
MRI can discriminate between clinically active and inactive JIA patients. However, physical examination is neither very sensitive nor specific in evaluating JIA disease activity compared with MRI. Subclinical synovitis was present in >35 % of presumed clinically inactive patients.
• MRI is sensitive for evaluating juvenile idiopathic arthritis (JIA) disease activity. • Contrast-enhanced MRI can distinguish clinically active and inactive JIA patients. • Subclinical synovitis is present in 35.9 % of presumed clinically inactive patients. • Physical examination is neither sensitive nor specific in evaluating JIA disease activity.
European Radiology 10/2013; DOI:10.1007/s00330-013-3036-2 · 4.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infants are at risk of developing symptoms of Poor Neonatal Adaptation (PNA) after exposure to psychotropic drugs in utero. Such symptoms are largely similar after exposure to antidepressants, antipsychotics and benzodiazepines and consist of mostly mild neurologic, autonomic, respirator and gastro-intestinal abnormalities. Most symptoms develop within 48 hours after birth and last for 2-6 days. After exposure to Selective Serotonin Reuptake Inhibitors (SSRIs), mirtazapine or venlafaxine in utero, breastfeeding is presumably protective for development of PNA. The dosage of antidepressants does not seem to be related to the risk of PNA. In order to objectify possible symptoms of PNA, observation of mother and child at the maternity ward is advisable. If PNA symptoms do not occur, an observation period of 48-72 hours is sufficient. This applies to all types of psychotropic drugs. When PNA symptoms are present it is advisable to observe the infant until the symptoms are fully resolved. Observation can be performed by trained nurses using the Finnegan scoring list. This observation list should be administered every 8 hours. Interpretation of the scores should be carried out by a paediatrician. In most cases symptoms are non-specific. Therefore other diagnoses, such as infection or neurologic problems, have to be excluded. When there is any doubt on possible intoxications during pregnancy, toxicological urine screening is indicated. Most cases of PNA are mild, of short duration and self-limiting without need for treatment. Supporting measures such as frequent small feedings, swaddling and increase of skin to skin contact with the mother is usually sufficient. In case of severe PNA it is advised to admit the infant to the Neonatal Care Unit (NCU). Phenobarbital is a safe therapeutic option. There seem to be no major long term effects; however, additional studies are necessary in order to draw definite conclusions.
[Show abstract][Hide abstract] ABSTRACT: Objectives. To evaluate differences in baseline characteristics between etanercept- and adalimumab-treated JIA patients and to reveal factors that influence the choice between these TNF inhibitors, which are considered equally effective in the recent ACR recommendations for JIA treatment.Methods. Biologic-naïve JIA patients with active arthritis who started treatment with adalimumab or etanercept between March 2008 and December 2011 were selected from the Dutch Arthritis and Biologicals in Children register. Baseline characteristics were compared. Focus group interviews with paediatric rheumatologists were performed to evaluate factors determining treatment choices.Results. A total of 193 patients started treatment with etanercept and 21 with adalimumab. Adalimumab-treated patients had longer disease duration prior to the start of biologics (median 5.7 vs 2.0 years) and more often a history of uveitis (71% vs 4%). Etanercept-treated patients had more disability at baseline (median Childhood Health Assessment Questionnaire score 1.1 vs 0.4) and more active arthritis (median number of active joints 6 vs 4). The presence of uveitis was the most important factor directing the choice towards adalimumab. Factors specific for the paediatric population-such as painful adalimumab injections-as well as the physician's familiarity with the drug accounted for the preference for etanercept.Conclusion. Although the two TNF inhibitors are considered equally effective, in daily practice etanercept is most often prescribed; adalimumab is mainly preferred when uveitis is present. In choosing the most suitable biologic treatment, paediatric rheumatologists take into account drug and patient factors, considering newly published data and cautiously implementing this into daily care.