Integrated treatment of first episode psychosis with online training (e-learning): study protocol for a randomised controlled trial

BackgroundThe integrated treatment of first episode psychosis has been shown to improve functionality and negative symptoms in previous studies. In this paper, we describe a study of integrated treatment (individual psychoeducation complementary to pharmacotherapy) versus treatment as usual, comparing results at baseline with those at 6-month re-assessment (at the end of the study) for these patients, and online training of professionals to provide this complementary treatment, with the following objectives: 1) to compare the efficacy of individual psychoeducation as add-on treatment versus treatment as usual in improving psychotic and mood symptoms; 2) to compare adherence to medication, functioning, insight, social response, quality of life, and brain-derived neurotrophic factor, between both groups; and 3) to analyse the efficacy of online training of psychotherapists.Methods/designThis is a single-blind randomised clinical trial including patients with first episode psychosis from hospitals across Spain, randomly assigned to either a control group with pharmacotherapy and regular sessions with their psychiatrist (treatment as usual) or an intervention group with integrated care including treatment as usual plus a psychoeducational intervention (14 sessions). Training for professionals involved at each participating centre was provided by the coordinating centre (University Hospital of Álava) through video conferences. Patients are evaluated with an extensive battery of tests assessing clinical and sociodemographic characteristics (Positive and Negative Syndrome Scale, State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, Hamilton Rating Scale for Depression, Scale to Assess Unawareness of Mental Disorders, Strauss and Carpenter Prognostic Scale, Global Assessment of Functioning Scale, Morisky Green Adherence Scale, Functioning Assessment Short Test, World Health Organization Quality of Life instrument WHOQOL-BREF (an abbreviated version of the WHOQOL-100), and EuroQoL questionnaire), and brain-derived neurotrophic factor levels are measured in peripheral blood at baseline and at 6 months. The statistical analysis, including bivariate analysis, linear and logistic regression models, will be performed using SPSS.DiscussionThis is an innovative study that includes the assessment of an integrated intervention for patients with first episode psychosis provided by professionals who are trained online, potentially making it possible to offer the intervention to more patients.Trial registrationNCT01783457 clinical trials.gov. Date of registration in primary registry 23 January 2013

Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa.

PURPOSE:To test the efficacy of systemic gene delivery of a mutant form of erythropoietin (EPO-R76E) that has attenuated erythropoietic activity, in a mouse model of autosomal dominant retinitis pigmentosa. METHODS:Ten-day old mice carrying one copy of human rhodopsin with the P23H mutation and both copies of wild-type mouse rhodopsin (hP23H RHO+/-,mRHO+/+) were injected into the quadriceps with recombinant adeno-associated virus (rAAV) carrying either enhanced green fluorescent protein (eGFP) or EpoR76E. Visual function (electroretinogram) and retina structure (optical coherence tomography, histology, and immunohistochemistry) were assessed at 7 and 12 months of age. RESULTS:The outer nuclear layer thickness decreased over time at a slower rate in rAAV.EpoR76E treated as compared to the rAAV.eGFP injected mice. There was a statistically significant preservation of the electroretinogram at 7, but not 12 months of age. CONCLUSIONS:Systemic EPO-R76E slows death of the photoreceptors and vision loss in hP23H RHO+/-,mRHO+/+ mice. Treatment with EPO-R76E may widen the therapeutic window for retinal degeneration patients by increasing the number of viable cells. Future studies might investigate if co-treatment with EPO-R76E and gene replacement therapy is more effective than gene replacement therapy alone

Systemic rAAV.EpoR76E preserves ONL thickness.

<p>A-C) OCT images (A, B) and quantification (C) in 7-month old hP23H <i>RHO</i>^+/-,m<i>RHO</i>^+/+ mice. D-F) OCT images (D,E) and quantification (F) in 12-month old hP23H <i>RHO</i>^+/-,m<i>RHO</i>^+/+ mice. Bars in images indicate ONL thickness. ***p<0.001.</p

Systemic rAAV.EpoR76E preserves scotopic ERG amax.

<p>A) Representative waveforms from 7 month old hP23H <i>RHO</i>^+/-,m<i>RHO</i>^+/+ mice at 2.88 cd•s/m². B) Quantification of the ERG amax at 0, 1, and 2.88 cd•s/m² in wild-type and 7- month old hP23H <i>RHO</i>^+/-,m<i>RHO</i>^+/+ mice. ***p<0.001. C) Quantification of the scotopic ERG bmax in wild-type and 7-month old hP23H <i>RHO</i>^+/-,m<i>RHO</i>^+/+ mice. D) Quantification of photopic bmax in wild-type and 12-month old hP23H <i>RHO</i>^+/-,m<i>RHO</i>^+/+ mice.</p

Systemic rAAV.EpoR76E has no effect on opsin localization or glial reactivity.

<p>Representative fluorescence micrographs near the optic nerve of 12-month old hP23H <i>RHO</i>^+/-,m<i>RHO</i>^+/+ mice treated with rAAV.eGFP (A, C, E), or rAAV.EpoR76E (B, D, F) labeled with DAPI (blue) and anti-rhodopsin (red; A, B), anti-M/L and anti-S-cone opsins (green; C,D), or anti-GFAP (red; E,F). Scale bar represents 50μm. Examples of microglial infiltration into the ONL in 12-month old hP23H <i>RHO</i>^+/-,m<i>RHO</i>^+/+ mice treated with rAAV.eGFP (G), or rAAV.EpoR76E (H), DAPI (blue), anti-IBA1 (red). Scale bar represents 25 μm.</p