Pharmacogenomic predictors of citalopram treatment outcome in major depressive disorder

Objectives. A significant proportion of patients with major depressive disorder (MDD) do not improve following treatment with first-line antidepressants and, currently, there are no objective indicators of predictors of antidepressant response. The aim of this study was to investigate pre-treatment peripheral gene expression differences between future remitters and non-responders to citalopram treatment and identify potential pharmacogenomic predictors of response. Methods. We conducted a gene expression study using Affymetrix HG-U133 Plus2 microarrays in peripheral blood samples from untreated individuals with MDD (N = 77), ascertained at a community outpatient clinic, prior to an 8-week treatment with citalopram. Gene expression differences were assessed between remitters and non-responders to treatment. Technical validation of significant probesets was carried out by qRT-PCR. Results. A total of 434 probesets displayed significant correlation to change in score and 33 probesests were differentially expressed between eventual remitters and non-responders. Probesets for SMAD 7 (SMA- and MAD-related protein 7) and SIGLECP3 (sialic acid-binding immunoglobulin-like lectin, pseudogene 3) were the most significant differentially expressed genes following FDR correction, and both were down-regulated in individuals who responded to treatment. Conclusions. These findings point to SMAD7 and SIGLECP3 as candidate predictive biomarkers of antidepressant response.     

Assessment of the test-retest reliability and construct validity of a modified WOMAC index in knee osteoarthritis

OBJECTIVE: To assess the test-retest reliability and the construct validity of a modified version of the French-Canadian version of the WOMAC index. METHODS: Open prospective study conducted in departments of Rheumatology, Rehabilitation and Orthopedic surgery of a tertiary care teaching hospital. Eighty-eight patients with symptomatic knee osteoarthritis (OA) fulfilling the revised criteria of the American College of Rheumatology were included. The French-Canadian version of the WOMAC index was completed twice at a 3-h interval. Impairment outcome measures, patients' perceived discomfort in walking and handicap were recorded. An item-by-item analysis was performed. Test-retest reliability was assessed using the intra-class correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using the Spearman rank correlation coefficient and a factor analysis was performed. RESULTS: Eight questions assessing function (section C) and the two questions assessing stiffness (section B) had insufficient psychometric properties and were excluded. Although test-retest reliability of the questionnaire was fair to good (0.82, 0.85, for the WOMAC section A, and modified section C, respectively), construct validity could not be demonstrated. Factor analysis of the modified form of the WOMAC extracted four factors, which differed from the a priori stratification. However, factor analysis of the modified section C extracted two factors explaining 68.4% of the variance, which could be clinically characterized. CONCLUSION: Despite its good test-retest reliability, the modified WOMAC index is not valid for assessing pain and disability induced by knee OA in a French population. Section A and modified section C could be used separately to assess, respectively, pain and function.     

Évaluation de la reproductibilité et de la validité de construit d’une forme modifiée de l’indice algofonctionnel de Lequesne dans l’arthrose du genouAssessment of the test-retest reliability and construct validity of a modified Lequesne index in knee osteo-arthritis

Objectives. – To assess the test-retest reliability and the construct validity of a modified version of the Lequesne index.Methods. – Patients with symptomatic knee osteo-arthritis fulfilling the revised criteria of the american college of rheumatology completed the Lequesne index twice at a 3 h interval. Impairment outcome measures and patients’ perceived discomfort in walking and handicap were recorded. An item by item analysis was performed. Items having insufficient psychometric properties were excluded. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using Spearman rank correlation coefficient and a factor analysis was performed.Results. – Eighty-eight patients were included. One question assessing pain (question IE) had a weak reliability (Kappa = 0.39) and was excluded. The test-retest reliability of the modified questionnaire was excellent (ICC = 0.95). Expected convergent and divergent correlations were achieved excepted for Vas pain and Vas handicap (0.46 and 0.40 respectively), and the “a priori” double stratification was confirmed by factor analysis, explaining 48.7% of the variance.Conclusion. – The modified form of the Lequesne index has sufficient psychometric properties to be used to assess pain and function in knee osteo-arthritis in a french population.     

Structural characterisation of a new heparinisable material based on ethylene/vinyl alcohol/vinyl acetate terpolymer and a poly(amido-amine)

Partially hydrolyzed ethylene/vinyl acetate copolymers (EVALVA) were modified by covalent binding of a heparin-complexing poly(amido-amine) (N₂LL). The physicochemical characterisation of the starting and modified materials was carried out through thermal analysis, dynamic mechanical thermal analysis, mechanical tensile test, contact angle, potentiometric measurements, water uptake and FT-IR spectroscopic measurements. The behaviour of this material in both the dry and the wet state was stressed, evidencing the different orientation of the chemical groups, which are buried or exposed according to whether its nature is hydrophilic or hydrophobic. The material was heparinised, and the presence of heparin was revealed by energy dispersive X-ray analysis (EDAX) and FT-IR.     

Determination of the intensity of X- and gamma-ray emissions in the decay of 153Sm.

The activity of a 153Sm solution was determined by means of liquid scintillation counting and an ionization chamber. Several accurately calibrated X- and gamma-ray spectrometers were used to measure point sources. The use of different detectors results in improvements to the accuracy of the data around 100 keV where the efficiency curve changes significantly. Photon emission intensities have been derived for the main X- and gamma-rays, and the 103-keV emission has a measured intensity of (29.07 (20)) per 100 disintegrations.     

Responsiveness of the French version of the Disability of the Arm, Shoulder and Hand questionnaire (F-DASH) in patients with orthopaedic and medical shoulder disorders

ObjectiveTo assess the responsiveness of the French version of the Disability of the Arm, Shoulder and Hand-Disability/Symptom (F-DASH-D/S) scale in patients with shoulder disorders.MethodsThis prospective study involved 2 groups of patients attending a tertiary care rehabilitation unit for treatment; an orthopaedic group of 47 patients with nonsurgical impacted proximal humeral fracture and a medical group of 26 patients with degenerative shoulder disorders. At 6 and 12 weeks after fracture in the orthopaedic group and at baseline and at a mean of 7.8 (SD 3.9) weeks after treatment in the medical group, patients underwent testing for the F-DASH-D/S scale, pain, active range of motion (ROM) and patient's perceived handicap. Sensitivity of the F-DASH-D/S was determined by the use of the standardized response mean (SRM) and effect size (ES). Clinical relevance was assessed by correlating the change in all outcome measures individually with change in patient's perceived handicap as an external indicator.ResultsBoth groups showed a significant improvement in the F-DASH-D/S score, active ROM and patient's perceived handicap. The sensitivity of the F-DASH-D/S was excellent, with SRM and ES values of 1.7 and 1.2 for the orthopaedic group and 1.2 and 1.3 for the medical group, respectively. For both groups, the F-DASH-D/S score gave the best correlation between change in patients' perceived handicap and change in other outcome parameters.ConclusionThe French version of the DASH-D/S scale is responsive and appropriate for assessing the effects of local and physical treatments on disability in orthopaedic and degenerative shoulder disorders.