Physical activity, functional ability, and disease activity in children and adolescents with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic condition known to cause pain-related complications in youth and affect children's physical functioning. There is no data in Arabic children with JIA about the impact of illness upon their physical activity. The objective of this study was to explore physical activity (PA) in children and adolescents with JIA compared with a healthy population and to examine associations between PA, functional ability, and disease activity. Our study included patients with JIA and group control aged between 8 and 17 years. The diagnosis was used according to the International League of Association of Rheumatology (ILAR) criteria 2001. Sociodemographic data and clinical features were collected. Physical activity level and energy expenditure were assessed with a 1-day activity diary and the metabolic equivalent (MET), respectively. Functional ability was assessed with the Moroccan version of the Childhood Health Assessment Questionnaire (CHAQ). Disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS). Fifty patients and 50 controls were included (mean ± SD age 11.5 ± 3.3 and 10.5 ± 3.8 years, respectively; p = 0.49) with masculine predominance n = 30 (59.6 %) and n = 29 (58 %), respectively (p = 0.26). The median disease duration was 4.3 years (2-5). The median analog scale (VAS) pain was 20 (10-40). Fourteen patients (28 %) had an active disease. Patient population consisted in majority of oligoarticular arthritis (28 %), 14 patients. The mean of energy expenditure and physical activity were significantly higher in the JIA group. The JIA group spent more time in bed and less time on moderate to vigorous PA than the control group. There is no significant relationship between PA, functional ability, and disease activity. Our study suggests that children and adolescents with JIA have low PA levels and are at risk of losing the benefits of PA. Low PA is not related to functional ability, disease duration, and disease activity in children and adolescent with JIA. A large cohort is necessary to confirm these results.

Factors influencing the quality of life of Moroccan patients with juvenile idiopathic arthritis.

The aim of our study is to investigate the factors influencing the quality of life, assessed by the Pediatric Quality of Life Inventory 4.0 (PedsQL4) Generic Score Scales, in Moroccan patients with juvenile idiopathic arthritis. This is a cross-sectional study conducted between January and June 2012, covering children with juvenile idiopathic arthritis (JIA) seen at the consultations of El Ayachi Hospital and Children's Hospital of the University Hospital of Rabat. Quality of life is assessed by the PedsQL4 which is a questionnaire composed of 23 items, completed by the child and the parent; the response to each item ranges from 0 to 100, so that higher scores indicate a better quality of life. The functional impact is assessed by the Childhood Health Assessment Questionnaire (CHAQ), and the disease activity by the number of tender and swollen joints, visual analogue scale (VAS) activity, erythrocyte sedimentation rate (ESR), and C-reactive protein. Forty-seven patients are included; the average age of the patients is 11 ± 3.35 years, and 40.4 % are females, with a median disease duration of 4 (2; 6) years. The oligoarticular form presents 26.7 %, the systemic form 24.4 %, and the enthesic form 22.2 %. The median of PedsQL4 is 80.43 (63.19; 92.93), and the median of the CHAQ is 0 (0; 1). Our study shows that some clinical and biological characteristics have significant effects on PedsQL by both parent and child reports. This study suggests that the achievement of the quality of life of our patients with JIA depends on the disease activity measured by swollen joints, the number of awakenings, parent VAS, physician VAS, patient VAS, and the ESR.

Sleep and its relationship to pain, dysfunction, and disease activity in juvenile idiopathic arthritis.

The objective of this study was to determine the sleep abnormalities that may exist in Moroccan children with juvenile idiopathic arthritis (JIA) and their relationship to pain, dysfunction, and disease activity. Case control study including 47 patients diagnosed with JIA, according to the criteria of the International League of Associations for Rheumatology (ILAR), and 47 healthy children, age and sex matched. Sleep was assessed by Children's Sleep Habits Questionnaire (CSHQ). All parents have filled the 45 items of the CSHQ and grouped into eight subscales: bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, sleep-disordered breathing, night awakenings, parasomnias, and morning awakening/daytime sleepiness. The disease activity was assessed by the number of painful joints, swelling joints, erythrocyte sedimentation rate, c-protein reactive, and Juvenile Arthritis Disease Activity Score (JADAS). Functional assessment was based on the value of Childhood Health Assessment Questionnaire. Pain was assessed by visual analog scale pain. Forty-seven patients were included, with 28 males (59.6 %). Children with JIA had a total score of CSHQ significantly higher than the control cases (p < 0.0001); significant differences were also found in the subscale sleep onset delay, sleep anxiety, sleep-disordered breathing, night awakenings, and parasomnias with a p value of <0.0001, 0.034, <0.0001, 0.001, and 0.00, respectively. Significant association was found between the CSHQ total score and visual analog scale (VAS) physician activity (p = 0.016) and JADAS (p = 0.05). There was a correlation between the sleep-disordered breathing and JADAS (p = 0.04). Sleep onset delay was associated with VAS patient pain (p = 0.05), as nocturnal awakenings and VAS patient pain (p = 0.016). Finally, parasomnias and physician's VAS activity (p = 0.015) and VAS patient pain (p = 0.03) were also correlated. This study suggests that sleep abnormalities are common in children with JIA. Strategies to improve sleep should be studied as a possible tool of improving the quality of life of children with rheumatic disease.

The uveitis and its relationship with disease activity and quality of life in Moroccan children with juvenile idiopathic arthritis.

The aim of our study is to investigate ocular involvement in juvenile idiopathic arthritis (JIA) and its relationship with disease activity and quality of life in Moroccan patients who suffer from JIA. This is a cross-sectional study conducted between January and June 2012 which includes patients with juvenile idiopathic arthritis (n = 30). All patients have undergone clinical and paraclinical assessment of JIA and a complete eye examination. Functional impairment is assessed by the Childhood Health Assessment Questionnaire while visual function is studied by the Effect of Youngsters' Eyesight in Quality of Life instrument (EYE-Q). Quality of life is assessed using the Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0). Four patients (13.33 %) have uveitis with a confidence interval between 3.4 and 30.7. Involvement is bilateral in three children (75 %). One patient (25 %) has elevated intraocular pressure with loss of the right eye due to glaucoma. There is a strong but not significant relationship between uveitis and the number of awakenings (r = 0.71, p = 0.69) and morning stiffness (r = 3.05, p = 0, 21). This relationship is moderate with erythrocyte sedimentation rate (r = 0.48, p = 0.78) and C-reactive protein (r = 0.25, p = 0.88). A strong but not significant association is found between the overall quality of life assessed by the PedsQL 4.0 and visual function assessed by EYE-Q in the uveitis group (r = -0.64, p = 0.55). This study suggests that uveitis associated with JIA can present serious complications and could have a direct relationship with the activity of the JIA as well as with the quality of life of the patient.

Selective and potent monoamine oxidase type B inhibitors: 2-substituted 5-aryltetrazole derivatives.

Twenty new 2-(cyanoalkyl)tetrazoles (15 and 16) and twenty new 2-(hydroxyalkyl)tetrazoles (17 and 18) were synthesized and investigated in vitro for their abilities to inhibit selectively rat brain monoamine oxidase (MAO) B over MAO A. Most of them were MAO B inhibitors and those bearing a substituted 4-(arylmethoxy)phenyl group in the position 5 of the tetrazole ring had IC50 values between 8 microM for 18d and 2 nM for 16a (30 nM for lazabemide) with a selectivity toward MAO B of 37,000 for 16a. The reversibility of their inhibitory activity was demonstrated by in vitro dialysis tests. The 5-[4-(phenylmethoxy)phenyl]-2-(2-cyanoethyl)tetrazole (16a) its derivative 16h and the 5-[4-(phenylmethoxy)phenyl]-2-(2-hydroxyethyl)tetrazole (18a) and its derivative 18h were found to be potent, in vitro selective, and competitive MAO B inhibitors. Tetrazole 16a can be considered one of the most active and selective competitive MAO B inhibitors known up to now. This compound was selected for ex vivo experiments and was shown to be a strong and reversible MAO B inhibitor with a short duration of action after oral administration at 5 mg/kg. The structure-activity approach gives rise to the great importance of lipophilicity over electronic effects of the compounds in these series.

5-[4-(benzyloxy)phenyl]-1,3,4-oxadiazol-2(3H)-one derivatives and related analogues: new reversible, highly potent, and selective monamine oxidase type B inhibitors.

Thirty-three new 5-[4-(benzyloxy)phenyl]-1,3,4-oxadiazol-2(3H)-one derivatives including related analogues, designed as inhibitors of monoamine oxidase type B (MAO B), were synthesized and investigated both in vitro and ex vivo for their abilities to inhibit selectively rat brain MAO B over MAO A. Three inhibitors were found to act as reversible, highly potent, and selective MAO B inhibitors, namely the nitrile derivative 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-one (12a) and two closely related homologues, the corresponding oxadiazolethione 13a and the alcohol 14b. Their IC50 (MAO B) values are in the low nanomolar range of 1.4-4.6 nM and their selectivities, estimated by the ratio of IC50 values (A/B), are from 3200 to > 71,400. Compound 12a exhibited the highest activity against MAO B. Its IC50 was evaluated to be 1.4 nM with a quasitotal selectivity (> 71,400) toward this enzyme. In ex vivo studies, 12a showed a reversible and short duration of action. MAO B was markedly inhibited with the oral dose of 1 mg/kg without any alteration of MAO A, and the inhibition almost did not exceed 24 h. Its ED50 (1 h after oral administration) was evaluated to be 0.56 mg (1.7 mumol)/kg. Remarkably, MAO A was not affected at doses as high as 1500 mg/kg, po. In addition, no apparent toxicity or behavioral anomaly was observed during the treatment even at the maximum administrated dose. SAR studies emphasize the existence of three binding sites to the enzyme with a special importance of the terminal phenyl. Analysis of the inhibition kinetics indicated that 12a acts in a two-step mechanism as a competitive, slow, and tight-binding inhibitor of MAO B with a Ki value of 0.22 microM and an overall Ki* value at equilibrium of 0.7 nM.