Normal sonoanatomy of small joints in healthy children: changes in cartilage and vascularisation according to age and gender.

OBJECTIVES: The metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints may be involved in juvenile idiopathic arthritis. Our goal was to describe their normal sonoanatomy in healthy children, according to age and gender. METHODS: We studied 41 consecutive healthy children (20 girls, 21 boys; age 2-15 years) divided into four age groups: 2-4 years (n=9), 5-7 years (n=11), 8-12 years (n=12), and 13-15 years (n=9). Longitudinal ultrasound axis of the MCP and MTP joints were obtained. The evolution of the cartilage thickness and vascularisation of these joints were studied according to age and gender. The MCP or MTP joints were the statistical unit. RESULTS: At all sites, on B-mode images, cartilage thickness was associated with age (p<0.0001). Cartilage thickness at different sites was significantly greater in boys than in girls (p≤0.05). Blood vessels were seen within the cartilage, with differences across age groups. CONCLUSIONS: This study provides children's age- and gender-specific sonoanatomy data of MCP and MTP and confirms the importance of using colour Doppler or Power Doppler to study cartilage vascularisation.

Normal sonoanatomy of the paediatric entheses including echostructure and vascularisation changes during growth.

OBJECTIVES: To describe the sonoanatomy of paediatric lower-limb entheses according to age and gender. We studied sites that most commonly involved entheses in spondyloarthritis. METHODS: We studied 41 consecutive healthy children (20 girls, 21 boys; age 2-15 years) divided into four age groups: 2-4 years (n = 9), 5-7 years (n = 11), 8-12 years (n = 12) and 13-15 years (n = 9). Ultrasound was used to obtain both transverse and longitudinal views of each enthesis. We assessed the echostructural components of the lower limb entheses and the vascularisation of the entheses and cartilage according to the different anatomical sites and age and gender. RESULTS: At all sites on B-mode, cartilage and tendon thicknesses showed positive or negative correlations with age (P < 0.0001). Side-to-side correlations were good (P < 0.0001 overall) and stronger for cartilage (r, 0.77-0.97) than for tendon thickness (r, 0.58-0.63). Agreement between the two sides for discrete data was very good to excellent (kappa, 0.77-1). Cartilage thickness at the various sites was significantly greater in boys than in girls (P ≤ 0.05). Tendon thickness was not significantly influenced by gender. Blood vessels were seen within the cartilage with differences across age groups. CONCLUSIONS: This study provides the first data on normal entheseal sonoanatomy and vascularisation in children. KEY POINTS: • The tendons of children exhibit the same fibrillar structure as adults • Tendon thickness at enthesis insertion in children is not influenced by gender • Cartilage thickness in children decreases with advancing age and varies with gender.

[Nurses in telehealth]. / Expérience infirmière en télésanté.

The development of telehealth is gathering pace. Advice, telemonitoring, support, as well as teleconsultations or even telediagnosis help to improve access to care across the health territories. The nursing team of a telehealth platform based in Lorraine presents this new area of practice.

Inhibition/activation in bipolar disorder: validation of the Multidimensional Assessment of Thymic States scale (MAThyS).

BACKGROUND: One of the major issues in clinical practice is the accurate differential diagnosis between mixed states and depression, often leading to inappropriate prescriptions of antidepressants in mixed states, and as a consequence, increasing the risk of manic switch and suicide. In order to better define the spectrum of mixed states, it may be useful to develop a dimensional approach. In this context, the MAThyS (Multidimensional Assessment of Thymic States) scale was built to assess activation/inhibition levels in all bipolar mood episodes, and to determine whether a clinical description in terms of activation/inhibition can help better define bipolar states with which both manic and depressive symptoms are associated. The aim of this paper is the validation of the MAThyS scale in 141 bipolar patients in acute states (manic, hypomanic, mixed, or depressive). METHODS: The validation of the MAThyS scale was the primary outcome of this 24-week, phase III, open-label, olanzapine single-arm clinical trial. Principal component, factorial analysis, and Cronbach's coefficient calculation (internal consistency) were performed. Concurrent validity (correlations with 17-item Hamilton Depression Rating Scale [HAMD-17], Hamilton Anxiety Rating Scale [HAMA], and Young Mania Rating Scale [YMRS]) and responsiveness to the clinical intervention were assessed (change in MAThyS scale and effect size) at 6 and 24 weeks. RESULTS: Scree plot of eigenvalues identified a 2-dimension structure ("activation/inhibition level" and "emotional component"). Psychometric properties were good: Cronbach's coefficient was >0.9. Concurrent validity was good with low correlation (-0.19) with the HAMA scale and a higher correlation at baseline with the YMRS (0.72) and HAMD-17(-0.43). As expected, the activation state was predominant in manic, hypomanic, and mixed states while inhibition was predominant in depressive states. MAThyS score improvement was observed (effect size: -0.3 at 6 and 24 weeks). CONCLUSIONS: The MAThyS demonstrated good psychometric properties. The MAThyS scale may help clinicians to better discriminate and follow bipolar episodes, especially the broad spectrum of mixed episodes.

Suicidal attempts in bipolar disorder: results from an observational study (EMBLEM).

OBJECTIVES: To compare patients with and without a history of suicidal attempts in a large cohort of patients with bipolar disorder and to identify variables that are associated with suicidal behavior. METHODS: European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) is a two-year, prospective, observational study that enrolled 3,684 adult patients with bipolar disorder and initiated or changed oral treatment for an acute manic/mixed episode. Of those, 2,416 patients were eligible for the two-year follow-up. Only baseline characteristics were studied in the present study, included sociodemographic data, psychiatric history and comorbidities, history of suicide attempts, history of substance use problems, compliance with treatment, inpatient admissions, and functional status. Symptom severity was assessed using the Clinical Global Impression-Bipolar Disorder (CGI-BP) scale, the Young Mania Rating Scale (YMRS), and the 5-item Hamilton Depression Rating Scale (HAMD-5). A logistic regression model identified baseline variables independently associated with a history of suicidal behavior. RESULTS: Of the 2,219 patients who provided data on their lifetime history of suicide attempts, 663 (29.9%) had a history of suicidal behavior (at least one attempt). Baseline factors associated with a history of suicidal behavior included female gender, a history of alcohol abuse, a history of substance abuse, young age at first treatment for a mood episode, longer disease duration, greater depressive symptom severity (HAMD-5 total score), current benzodiazepine use, higher overall symptom severity (CGI-BP: mania and overall score), and poor compliance. CONCLUSIONS: These factors may be considered as potential characteristics to identify subjects at risk for suicidal behavior throughout the course of bipolar disorder.

Mixed states vs. pure mania in the French sample of the EMBLEM study: results at baseline and 24 months--European mania in bipolar longitudinal evaluation of medication.

BACKGROUND: To describe the clinical course and treatment patterns over 24 months of patients experiencing an acute manic/mixed episode within the standard course of care. METHODS: EMBLEM was a 2-year European prospective, observational study on outcomes of patients experiencing a manic/mixed episode. Adults with bipolar disorder were enrolled within the standard course of care as in/outpatients if they initiated or changed oral medication for treatment of acute mania. After completing 12 weeks of acute phase, patients were assessed every 3-6 months during the maintenance phase. We present the 24 month results, with subgroup analysis for mixed states (MS) and pure mania (PM). These subgroup analyses are driven by the high proportion of antidepressants prescribed in this cohort. RESULTS: In France, 771 patients were eligible for the maintenance phase. 69% of patients completed the follow up over 24 months. The mean age was 45.5 years (sd = 13.6) with 57% of women. 504 (66%) patients were experiencing a PM and 262 (34%) a MS at baseline. The main significant differences in MS vs. PM at baseline were: a higher rate of women, and in the previous 12 months, a higher frequency of episodes (manic/mixed and depressive), more suicide attempts, more rapid cycling, fewer social activities and more work impairment. Over the 24 months of follow-up the MS group had a significantly lower recovery than PM (36% vs. 46%, p = 0.006). Overall, 42% of all patients were started on monotherapy and 58% on combination therapy; of those 35% and 30% respectively remained on their initial medication throughout the 24 months. At baseline, 36% were treated with an antidepressant, this proportion remains high throughout the follow-up period, with a significantly higher rate for MS vs. PM at 24 months (55% vs. 27%, p < 0.001). CONCLUSION: In this large sample, MS occur frequently (34%), they are more severe at baseline and have a worse functional prognosis than PM. Although antidepressants are not recommended in MS and PM, they were frequently prescribed at baseline and are maintained during the 24 months of follow-up.

Mixed states with predominant manic or depressive symptoms: baseline characteristics and 24-month outcomes of the EMBLEM cohort.

BACKGROUND: While factors associated with mixed states have been extensively studied, data are scant regarding the clinical heterogeneity of mixed states. The EMBLEM study was a prospective, observational study on patients with manic and mixed states. We describe and compare baseline characteristics and 24-month clinical course of mixed states with predominant depressive symptoms (MSDS) and mixed states with predominant manic symptoms (MSMS). METHODS: Adult inpatients/outpatients with bipolar disorder were enrolled within the standard course of care if they initiated or changed oral medication for acute mania or mixed states. A logistic regression was used to identify the baseline factors associated with each polarity. Comparisons with mixed episode without symptom predominance (OMS) were performed for informational purpose only. RESULTS: About 573 mixed patients were analyzed (23.7% of the cohort): 59.5% (n=341) had MSMS, 11.9% (n=68) had MSDS, and 28.6% (n=164) had OMS. At baseline, hallucinations/delusions during the index episode, inpatient status, high CGI-BP overall score, and low education level were more often associated with MSMS versus MSDS. Alcohol abuse or dependence and selective serotonin reuptake inhibitor (SSRI) or benzodiazepine use at inclusion were significantly more frequent with MSDS. MSDS had a significantly lower 24-month recurrence rate than MSMS; MSMS experienced more switches to mania whereas MSDS switched more to depression. LIMITATIONS: The post hoc dimensional definitions in the study require caution in the interpretation of the results. CONCLUSION: These results present evidence of clinical heterogeneity within mixed states. Predominant manic or depressive symptoms within mixed episode could influence clinicians' decisions in term of hospitalization, treatment, and perception of bipolar severity.

Young Mania Rating Scale: how to interpret the numbers? Determination of a severity threshold and of the minimal clinically significant difference in the EMBLEM cohort.

The aim of this analysis was to identify Young Mania Rating Scale (YMRS) meaningful benchmarks for clinicians (severity threshold, minimal clinically significant difference [MCSD]) using the Clinical Global Impressions Bipolar (CGI-BP) mania scale, to provide a clinical perspective to randomized clinical trials (RCTs) results. We used the cohort of patients with acute manic/mixed state of bipolar disorders (N = 3459) included in the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study. A receiver-operating characteristic analysis was performed on randomly selected patients to determine the YMRS optimal severity threshold with CGI-BP mania score ≥ "Markedly ill" defining severity. The MCSD (clinically meaningful change in score relative to one point difference in CGI-BP mania for outcome measures) of YMRS, was assessed with a linear regression on baseline data. At baseline, YMRS mean score was 26.4 (±9.9), CGI-BP mania mean score was 4.8 (±1.0) and 61.7% of patients had a score ≥ 5. The optimal YMRS severity threshold of 25 (positive predictive value [PPV] = 83.0%; negative predictive value [NPV] = 66.0%) was determined. In this cohort, a YMRS score of 20 (typical cutoff for RCTs inclusion criteria) corresponds to a PPV of 74.6% and to a NPV of 77.6%, meaning that the majority of patients included would be classified as severely ill. The YMRS minimal clinically significant difference was 6.6 points.

Outcome and safety of TNFα antagonist therapy in 475 consecutive outpatients (with rheumatoid arthritis or spondyloarthropathies) treated by a single physician according to their eligibility for clinical trials.

OBJECTIVE: To investigate the effectiveness and safety of TNFα antagonists in patients with rheumatoid arthritis (RA) or spondyloarthropathies (SpA) treated by a single physician, according to the presence of the inclusion and non-inclusion criteria used to select patients for pivotal clinical trials. METHODS: Effectiveness was evaluated based on four categories defined by the DAS28-ESR and BASDAI values, from a very good response (mean DAS-28-ESR less than 3.2 and mean BASDAI less than 2.0) to failure (DAS28-ESR unchanged or greater than 5.1 and BASDAI unchanged). Serious adverse events were defined as events that required permanent TNFα antagonist discontinuation or that led to sequelae, hospital admission, or death. RESULTS: The study included 475 patients, 230 with RA, 226 with SpA, 10 with juvenile-onset arthritis, and nine with unclassifiable arthritis. Mean number of TNFα antagonists used per patient was 1.3 and mean duration of TNFα antagonist treatment was 28±23 months. Overall, 41% of patients met the inclusion and non-inclusion criteria used in pivotal trials; the proportion was 43% in the RA group and 40% in the SpA group. These patients had a 3-fold higher rate of very good responses (54 versus 19%) and a 5-fold lower rate of failures (5 versus 25%) compared to the other patients. Of the 15 (3%) patients who died, none met pivotal trial criteria. The group that met pivotal trial criteria had a significantly lower rate of serious adverse events (11 versus 16%; Chi(2), p=0.0001), although age was similar in the two groups (53±16 years versus 57±14 years). CONCLUSION: Patients meeting the selection criteria used in pivotal trials had a higher response rate and significantly fewer serious adverse events.

Six-month response to anti-TNF drugs in axial spondylarthropathy according to the fulfillment or not of New-York criteria for ankylosing spondylitis or French recommendations for anti-TNF use. A "real life" retrospective study on 175 patients.

OBJECTIVES: To assess in clinical practice the 6-month outcome in patients with axial spondylarthropathy (SpA) treated by anti-TNF, according to the fulfillment of New-York criteria (NY) for the diagnosis of ankylosing spondylitis (AS), or agreement with French recommendations (SFR) for anti-TNF use in SpA. METHODS: Outcome could be retrospectively assessed according to the updated ASAS score (improvement of at least 50% or two units of the BASDAI) and the percentages of patients reaching at 6 month the patient BASDAI acceptable symptoms state (PASS) of 3.5. RESULTS: A total of 175 out of 203 patients could be retrospectively assessed at 6 month. Fifty-eight percent fulfilled the NY criteria, and 81% satisfied SFR recommendations. After 6 months of anti-TNF treatment, patients with NY criteria (NY+) met the updated ASAS outcome more often than NY- (70% versus 58%) (chi-square: 0.041): reduction of BASDAI of 2.86+/-2.18 (NY+) versus 2.48+/-2.39 (NY-) (NS). PASS of 3.5 was reached in 64% (NY+) versus 49% (NY-). ASAS outcome was met in 45%/60%/69%/88% of patients with 0/1/2/>/=3 parameters to guide physician's opinion from SFR: raised ESR or CRP was present in 66%, active enthesitis or arthritis in 49%, coxitis in 13%, active or relapsing uveitis in 11%, inflammation of sacro-iliac or spine on MRI in 12%, and worsening of articular damage in 5%. CONCLUSION: The effectiveness of TNF-blockers was slightly better in patients fulfilling the NY criteria for AS or SFR recommendations, but 58% of axial SpA not fulfilling NY criteria, and 48% of patients not satisfying French recommendations also met ASAS outcome.