Responsiveness of the EuroQol EQ-5D and Hospital Anxiety and Depression Scale (HADS) in rheumatoid arthritis patients receiving tocilizumab.

The aim of this study was to assess the responsiveness to change of the quality of life evaluated by the EuroQol Five Dimensions Questionnaire (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) after biological treatment in a population of rheumatoid arthritis patients. A cohort of patients with RA (n = 29) treated with tocilizumab (TCZ) were analyzed in the study. The inclusion criteria were patients aged between 18 and 65 years, fulfilling American College of Rheumatology 1987 criteria for RA. All patients had inadequate response to methotrexate and with no prior biologic exposure. They were evaluated clinically including Disease Activity Score 28 (DAS28), and the European Quality of Life 5 Dimensions (EQ-5D) to measure the quality of life, and HAD assessed the anxiety and depression status at the initiation of treatment with anti-IL 6 receptor antibody agent and after 6 months. Sensitivity to change was quantified by the effect size (ES) before and after the treatment with TCZ. Among 29 patients with RA included in the study, 25 were females and 4 males. The mean age was 42 years ± 13.4 (SD). Three patients were excluded from the study before 24 weeks because of serious side effects, and five have missing data. The study population exhibited significant decreases in all measures of disease activity at 24 weeks. Physical activity expressed by the Health Assessment Questionnaire (HAQ) score increased through the observation period (for all p < 0.001). Sensitivity to change was high for the VAS and EQ-5D (ES 1.58 and 1.36, respectively) but only moderate for the HAD anxiety component (ES = 0.70) and small for the HAD depression component (ES = 0.4). The EQ-5D and VAS were more responsive than HADS to evaluate the quality of life on patient with RA treated with TCZ.

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.

Sexual maturation in Moroccan patients with juvenile idiopathic arthritis.

Abnormal puberty is often reported in children suffering from many chronic diseases. Juvenile idiopathic arthritis (JIA) is the most common joint disorder in developing children. The aim of this study was to assess sexual maturation of Moroccan children with JIA and to compare the development of secondary sexual characteristics in children with JIA to children in the general population. Forty children with JIA and 74 healthy controls were included in a cross-sectional study. The diagnosis of JIA was made according to the criteria of the International League of Association of Rheumatology. Every child was examined for the development of genitalia as per criteria given by Tanner. The children with JIA were also divided into 3 groups: pre-puberty (stage 1), puberty (stages 2-3) and post-puberty (stage 4-5), and the association between puberty and cumulative dose of steroids, disease duration, disease activity, height, weight and age was investigated. Forty children with JIA were included (22 male, 18 female); the mean of age of the patients was 11 ± 4.23 years. Puberty in the patients (mean of tanner 2.43 ± 1.36) was lower than controls (2.55 ± 1.36). The prevalence of the children in prepuberty was of 15 (37.5 %) and 8 (20 %) in postpuberty. The prevalence of the children having a delayed puberty was of 6 (15 %) versus 1(1.4 %) in healthy controls (p = 0.005). There was an association between dose of corticosteroids, age at the administration of corticosteroids and the delayed puberty in boys (p = 0.009). In addition, there was no significant association in both sex between this poor puberty and duration of JIA (p = 0.45 in boys and p = 1.99 in girls) and its activity calculated by the DAS28 (p = 0.73 in boys and p = 1). Our study suggests that the puberty is retarded in Moroccan patients with JIA comparing to healthy children and that the dose of corticosteroid and the age at its administration may contribute to delayed puberty in boys.

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.

Fatigue in patients with ankylosing spondylitis: prevalence and relationships with disease-specific variables, psychological status, and sleep disturbance.

This study aims to evaluate the frequency of fatigue in Moroccan patients with ankylosing spondylitis (AS), and its relationships with disease-specific variables, psychological status, and sleep disturbance. A cross-sectional study included patients fulfilled the modified New York classification criteria for ankylosing spondylitis. To assess fatigue, the first item of Bath ankylosing spondylitis disease activity index (BASDAI) and the multidimensional assessment of fatigue (MAF) was used. The evaluation included the activity of the disease (BASDAI), global well-being (Bath ankylosing spondylitis global index), functional status (Bath ankylosing spondylitis functional index), metrologic measurements (Bath ankylosing spondylitis metrological index), and visual analog scale of axial or joint pain. The erythrocyte sedimentation rate and C-reactive protein were measured. To assess psychological status, the hospital anxiety and depression scale (HADS) was used. Sleep disturbance was assessed by the fourth item of Hamilton anxiety scale. One hundred and ten patients were included, of average age 38.0 years ± 12.6. In our data, 66.4% experienced severe fatigue (BASDAI fatigue ≥ 5). The mean total score of MAF was 26 ± 12.77. The disease-specific variables contributed significantly with both BASDAI fatigue and MAF as dependent variables, accounting for 71.3 and 65.6% of the variance, respectively. The contribution of the depression, anxiety, and sleep disturbance were 24.9, 18.4 and 15.4%, respectively. This study state the importance of fatigue in AS patients. Even though disease activity was the most powerful predictor of fatigue, the effects of psychogenic factors and sleep disturbance, should be taken into consideration in the management of AS.

The prevalence of vertebral fractures and health-related quality of life in postmenopausal women.

Vertebral fractures are the hallmark of osteoporosis, responsible for increased back pain, impairment of mobility and functional limitations. These factors have an impact on patients' health-related quality of life (QOL). The aim of this study was to evaluate the prevalence of vertebral fractures in Moroccan postmenopausal women and to assess their QOL, using an Arabic validated version of QUALEFFO. The study recruited 347 postmenopausal women in obvious good health. We excluded women who had used a drug or who had chronic diseases affecting bone metabolism. All patients had density measurements and spinal radiography. Each vertebral body (T4-L5) was graded using the semiquantitative method of Genant. The mean age was 60 years. Forty-six percent of patients had at least one vertebral fracture. The prevalence ranged from 31% in patients 50-55 years to 69% in patients 65 years and older. Patients with vertebral fractures were older (61.6 ± 8 vs 57 ± 7 years, P < 0.001), had more frequent history of nonvertebral fractures, and had spine and hip BMD values significantly lower (P < 0.001) than patients without vertebral fractures. In multivariate analysis, older age and a history of nonvertebral fractures were the two independent clinical factors of vertebral fractures. The number of fractures was a determinant of a low QOL, as indicated by an increased score in physical function, social function, mental function, and general health [for all (P < 0.05)]. Patients with higher grades of vertebral deformities, i.e., more severe fractures, had low QOL in these four domains. Patient with thoracolumbar fractures had a worse general health than patients with thoracic or lumbar fractures. We found a high prevalence of vertebral fractures probably explained by socioeconomic factors in Morocco. QOL, assessed by an osteoporosis-specific instrument, is decreased in postmenopausal women as a function of both the number and the severity of the vertebral fractures. Treating women with prevalent fractures may avoid a further decrease in their quality of life.

Hip involvement in juvenile idiopathic arthritis.

We analyzed the clinical, biological, and radiological aspects of hip involvement in juvenile idiopathic arthritis (JIA) in a developing country. The recruited patients fulfilled the International League Against Rheumatism criteria for the diagnosis of the JIA. Clinical, biological, and radiological parameters relating to the JIA were collected. Hip involvement was assessed according to clinical and radiological data related to hip disease. One hundred twenty-one patients were included (68 girls and 53 boys). The mean age of the disease onset was 9 +/- 4.2 years (1-16 years). The mean age of the patients at the time of the study was 15 +/- 10 years (2-46 years). The duration of the disease was 5 +/- 8.5 years (0.5-39 years). Forty cases (33%) of the hip involvement were noted. The mean age was 24 +/- 10.03 years (3-46 years); the sex ratio was 1:3. The mean duration of the hip disease was 0.6 +/- 3.6 years (3-14 years). Hip arthritis seemed to be more frequent in polyarticular and enthesitis-related arthritis. The severity of the hip involvement was significantly correlated with early disease onset, disease duration, subtypes, and high disability (for all these data p < 0.05). This study suggested that in JIA hip involvement was more frequent in enthesitis-related arthritis and polyarticular subtypes. It was correlated with the severity and the early disease onset of the JIA, which was similar to reported data.

Synthesis and 5-HT2A antagonist activity of derivatives of the novel heterocycles indolo[3,2-d]pyrrolo[3,2-g]azecine and benzo[d]pyrrolo[3,2-g]azecine compared to the benz[d]indolo[2,3-g]azecine derivative LE 300.

An indolo[3,2-d]pyrrolo[3,2-g]azecine and a benzo[d]pyrrolo[3,2-g]azecine analogue of the potent dopamine receptor antagonist LE 300 (7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine) have been prepared in multi-step reactions via C-N bond cleavage of corresponding quaternary N-methylquinolizinium iodides. LE 300, the target compounds and two precursor quinolizines have been tested in vitro for antagonist activity at 5-HT2A receptors (rat tail artery) and H1 receptors (guinea-pig ileum), respectively. LE 300 and compound 19 (3,6-dimethyl-4,5,6,7,8,13-hexahydro-3H-benzo[d]pyrrolo[3,2-g]azecine) competitively inhibited 5-HT-induced contractions with similar nanomolar potency (pA2 = 8.32 and 8.01, respectively) but were less active than the reference antagonist ketanserin (pA2 = 9.55). Compound 19 displayed moderate H1-antihistaminic activity in the guinea-pig ileum assay (pA2 = 7.37).