Successful development and testing of a Method for Aggregating The Reporting of Interventions in Complex Studies (MATRICS)

Objectives: To develop a tool for the accurate reporting and aggregation of findings from each of the multiple methods used in a complex evaluation in an unbiased way. Study Design and Setting: We developed a Method for Aggregating The Reporting of Interventions in Complex Studies (MATRICS) within a gastroenterology study [Evaluating New Innovations in (the delivery and organisation of) Gastrointestinal (GI) endoscopy services by the NHS Modernisation Agency (ENIGMA)]. We subsequently tested it on a different gastroenterology trial [Multi-Institutional Nurse Endoscopy Trial (MINuET)]. We created three layers to define the effects, methods, and findings from ENIGMA. We assigned numbers to each effect in layer 1 and letters to each method in layer 2. We used an alphanumeric code based on layers 1 and 2 to every finding in layer 3 to link the aims, methods, and findings. We illustrated analogous findings by assigning more than one alphanumeric code to a finding. We also showed that more than one effect or method could report the same finding. We presented contradictory findings by listing them in adjacent rows of the MATRICS. Results: MATRICS was useful for the effective synthesis and presentation of findings of the multiple methods from ENIGMA. We subsequently successfully tested it by applying it to the MINuET trial. Conclusion: MATRICS is effective for synthesizing the findings of complex, multiple-method studies.

Effectiveness of integrated cognitive remediartion therapy for schizophrenia outpatients: Early versus long-term course of illness – results from an international RCT

Background Nowadays there is extensive evidence available showing the efficacy of cognitive remediation therapies. Integrative approaches seem superior regarding the maintenance of proximal outcome at follow-up as well as generalization to other areas of functioning. To date, only limited evidence about the efficacy of CRT is available concerning elder schizophrenia patients. The Integrated Neurocognitive Therapy (INT) represents a new developed cognitive remediation approach. It is a manualized group therapy approach targeting all 11 NIMH-MATRICS dimensions within one therapy concept. In this study we compared the effects of INT on an early course group (duration of disease<5 years) to a long-term group of schizophrenia outpatients (duration of disease>15 years). Methods An international multicenter study carried out in Germany, Switzerland and Austria with a total of 90 outpatients diagnosed with Schizophrenia (DSM-IV-TR) were randomly assigned either to an INT-Therapy or to Treatment-As-Usual (TAU). 50 of the 90 Patients were an Early-Course (EC) group, suffering from schizophrenia for less than 5 years (Mean age=29 years, Mean duration of illness=3.3 years). The other 40 were a Long-term Course (LC) group, suffering from schizophrenia longer than 15 years (Mean age= 45 years, Mean duration of illness=22 years). Treatment comprised of 15 biweekly sessions. An extensive assessment battery was conducted before and after treatment and at follow up (1 year). Multivariate General Linear Models (GLM) (duration of illness x treatment x time) examined our hypothesis, if an EC group of schizophrenia outpatients differ in proximal and distal outcome from a LC group. Results Irrespective of the duration of illness, both groups (EC & LC) were able to benefit from the INT. INT was superior compared to TAU in most of the assessed domains. Dropout rate of EC group was much higher (21.4%) than LC group (8%) during therapy phase. However, interaction effects show that the LC group revealed significantly higher effects in the neurocognitive domains of speed of processing (F>3.6) and vigilance (F>2.4). In social cognition the EC group showed significantly higher effects in social schema (F>2.5) and social attribution (blame; F>6.0) compared to the LC group. Regarding more distal outcome, patients treated with INT obtained reduced general symptoms unaffected by the duration of illness during therapy phase and at follow-up (F>4.3). Discussion Results suggest that INT is a valid goal-oriented treatment to improve cognitive functions in schizophrenia outpatients. Irrespective of the duration of illness significant treatment, effects were evident. Against common expectations, long-term, more chronic patients showed higher effects in basal cognitive functions compared to younger patients and patients without any active therapy (TAU). Consequently, more integrated therapy offers are also recommended for long-term course schizophrenia patients.

Significance of social cognitive remediation therapy within a comprehensive treatment concept

Objectives: The final goal in the successful treatment of schizophrenia patients is defined in improved functional recovery. Thus the integration of social cognitive tasks within a comprehensive treatment concept should offer significant advantages in generalization and transfer of therapy effects. Recent therapy outcome research supports these advantages. Empirical modeling identified social cognition as a mediating factor between neurocognition and functional recovery. Regarding this, we first developed the Integrated Psychological Therapy Program (IPT). It consists of 5 subprograms and combines interventions on neurocognition, social cognition, and social competence. As a further development of the cognitive part of IPT we developed the Integrated Neurocognitive Therapy (INT), which focuses on all social and neurocognitive domains defined by MATRICS. Methods: The aim was to investigate whether the application of the complete IPT is superior in comparison to the use of single IPT subprograms. Data were based on 37 independent IPT studies including a total sample of 1692 schizophrenia patients. Additionally, the proximal outcome in cognitive domains as well as in more distal outcome areas was investigated in an international RCT on INT including 169 schizophrenia outpatients. Results: All IPT subprogram variations obtained significant effects in proximal outcome. Each subprogram domain reached the largest effects in the targeted area. With regard to distal outcomes, combinations of subprograms showed a significant reduction of negative symptoms and an improvement in not targeted areas of functioning. This strongly supports vertical generalization effects to other functional domains. Regarding INT, results support efficacy compared to TAU in various cognitive domains, in psychosocial functioning and symptoms after therapy and at 1-year-follow-up. Conclusion: Results support evidence for the efficacy of longer lasting integrated therapy. The success of these treatment concepts is strongly based on successful therapy of social cognitive functions.

State of the art of integrated therapy approaches in the treatment of schizophrenia: empirical evidence and clinical relevance

Objective: Integrated behavior therapy approaches are defined by the combination of behavioral and or cognitive interventions targeting neurocognition combined with other goal-oriented treatment targets such as social cognition, social skills, or educational issues. The Integrated Psychological Therapy Program (IPT) represents one of the very first behavior therapy approaches combining interventions of neurocognition, social cognition, and social competence. This comprehensive group-based bottom-up and top-down approach consists of five subprograms, each with incremental steps. IPT has been successfully implemented in several countries in Europe, America, Australia and in Asia. IPT worked as a model for some other approaches designed in the USA. IPT was undergone two further developments: based on the social competence part of IPT, the three specific therapy programs focusing residential, occupational or recreational topics were developed. Recently, the cognitive part of INT was rigorously expanded into the Integrated Neurocognitive Therapy (INT) designed exclusively for outpatient treatment: INT includes interventions targeting all neurocognitive and social cognitive domains defined by the NIMH-MATRICS initiative. These group and partially PC-based exercises are structured into four therapy modules, each starting with exercises on neurocognitive domains followed by social cognitive targets. Efficacy: The evidence of integrated therapy approaches and its advantage compared to of one-track interventions was becoming a discussion tool in therapy research as well as in mental health systems. Results of meta-analyses support superiority of integrated approaches compared to one-track interventions in more distal outcome areas such as social functioning. These results are in line with the large body of 37 independent IPT studies in 12 countries. Moreover, IPT research indicates the maintenance of therapy effects after the end of therapy and some evidence generalization effects. Additionally, the international randomized multi-center study on INT with 169 outpatients strongly supports the successful therapy of integrated therapy in proximal and distal outcome such as significant effects in cognition, functioning and negative symptoms. Clinical implication: therapy research as well as expert’s clinical experience recommends integrated therapy approaches such as IPT to be successful agents within multimodal psychiatric treatment concepts. Finally, integrated group therapy based on cognitive remediation seems to motivate and stimulate schizophrenia inpatients and outpatients to more successful and independent life also demanded by the recovery movement.

Cognitive remediation therapy: Does it generalize to significant outcome areas?

Objective: Cognitive remediation therapy (CRT) approaches have demonstrated to be effective in improving cognitive functions in schizophrenia. However, there is a lack of integrated CR approaches that target multiple neuro- and social-cognitive domains with a special focus on the generalization of therapy effects to functional outcome and negative symptoms. Method: This 8-site randomized controlled trial evaluated the efficacy of a novel cognitive-behavioral group therapy approach called integrated neurocognitive therapy (INT). INT includes manual-based exercises to improve all neuro- and social-cognitive domains as defined by the Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative by compensation and restitution. One hundred and fifty-six outpatients with a diagnosis of schizophrenia or schizoaffective disorder accord- ing to DSM-IV-TR were randomly assigned to receive 15 weeks of INT or treatment as usual (TAU). INT patients received 30 bi-weekly therapy sessions. Each session lasted 90min. Mixed models were applied to assess changes in neurocognition, social cognition, symptoms, and functional outcome at post-treatment and at 9-month follow-up. Results: Compared to TAU, INT patients showed significant improvements on multiple neuro- and social-cognitive domains, negative symptoms, and functional outcome after therapy and at 9-month follow-up. Number-needed-to-treat analyses indicate that only five INT patients are necessary to produce durable and meaningful improvements in functional outcome. Conclusions: Integrated interventions on neurocognition and social cognition have the potential to improve not only cognitive performance but also functional outcome and negative symptoms. These findings are important as treatment guidelines for schizophrenia have criticized CRT for their poor generalization effects.

Differential effectiveness of integrated cognitive remediation therapy for schizophrenbia outpatients: The impact oft he duration of illness

Background Nowadays there is extensive evidence available showing the efficacy of cognitive remediation (CR). To date, only limited evidence is available about the impact of the duration of illness on CR effects. The Integrated Neurocognitive Therapy (INT) represents a new developed CR approach. It is a manualized group therapy targeting all 11 NIMH-MATRICS domains. Methods In an international multicenter study, 166 schizophrenia outpatients (DSM-IV-TR) were randomly assigned either to INT or to Treatment-As-Usual (TAU). 60 patients were defined as Early Course group (EC) characterized by less than 5 years of illness, 40 patients were in the Long-Term group (LT) characterized by more than 15 years of illness, and 76 patients were in the Medium-Long-Term group (MLT) characterized by an illness of 5-15 years. Treatment comprised of 15 biweekly sessions. Assessments were conducted before and after treatment and at follow up (1 year). Multivariate General Linear Models (GLM) examined our hypothesis, whether EC, LT, and MLT groups differ under INT and TAU from each other in outcome. Results First of all, the attendance rate of 65% was significantly lower and the drop out rate of 18.5% during therapy was higher in the EC group compared to the other groups. Interaction effects regarding proximal outcome showed that the duration of illness has a strong impact on neurocognitive functioning in speed of processing (F>2.4) and attention (F>2.8). But INT intervention compared to TAU only had a significant effect in more chronically ill patients of MLT and LT, but not in younger patients in EC. In social cognitive domains, only the EC group showed a significant change in attribution (hostility; F>2.5), LT and MLT groups did not. However, no differences between the 3 groups were evident in memory, problem solving, and emotion perception. Regarding more distal outcome, LT patients had more symptoms compared to EC (F>4.4). Finally, EC patients showed higher improvements in psychosocial functioning compared to LT and MLT (F=1.8). Conclusions Against common expectations, long-term, more chronically ill patients showed higher effects in basal cognitive functions compared to younger patients and patients without any active therapy (TAU). On the other hand, early-course patients had a greater potential to change in attribution, symptoms and psychosocial functioning. Consequently, more integrated therapy offers are also recommended for long-term course schizophrenia patients.

Wirksamkeit kognitiver Remediationstherapie bei schizophren Erkrankten mit ausgeprägter Negativsymptomatik

Einleitung Die Behandlung von Negativsymptomen ist bei schizophren Erkrankten bis heute wenig erfolgsversprechend. Wenige Studien zeigen inkonsistente Befunde und berichten ausschliesslich über eine dimensionale Reduktion von Negativsymptomen, jedoch nicht über Remissionsraten bei ausgeprägter Negativsymptomatik. Gegenwärtig wird der mögliche Nutzen Kognitiver Remediationstherapie zur Behandlung von Negativsymptomen diskutiert. Die von unserer Arbeitsgruppe entwickelte Integrierte Neurokognitive Therapie (INT) stellt einen Kognitiven Remediationsansatz im Gruppensetting dar und vereint Interventionen zu allen kognitiven MATRICS-Dimensionen in einem einheitlichen Therapiekonzept. Methode In einer internationalen multizentrischen RCT mit 138 ambulanten schizophrenen Patienten (DSM IV-TR) wurde die INT mit einer Standardbehandlung (TAU) verglichen. In Anlehnung an die vorgeschlagenen PANSS-Kriterien der „Remission in Schizophrenia Working Group“ (RSWG) wurden aus der Stichprobe eine Gruppe mit ausgeprägten Negativsymtomen (GN) während der Baselineerhebung definiert (n=53). Als Referenz diente eine Gruppe mit persistierenden Positivsymptomen ohne Negativsymptome (GP, n=31) sowie eine remittierte Gruppe (RG, n=54) ohne Symptome. Eine Testbatterie zu kognitiven und sozialen Funktionen sowie ein PANSS-Interview wurden vor und nach der Therapiephase von 15 Wochen sowie nach einer Einjahreskatamnese erhoben, um die Wirksamkeit von INT bei Patienten mit ausgeprägter Negativsymptomatik zu quantifizieren. Ergebnisse 1) Symptomreduktion: in der Zielgruppe GN zeigten signifikant mehr INT-Patienten (55%) als TAU-Patienten (26%) während der Therapiephase eine Remission der Negativsymptomatik. Auch nach der Katamnese erzielte INT (82%) signifiaknt höhere Remissionsraten als TAU (50%). Dagegen waren in GP keine signifikanten Symptomreduktionen gegenüber TAU nachweisbar. In RG waren signifikant geringere Rückfallraten (Symptomanstieg) bei INT (13%) gegenüber TAU (50%) nach der Therapie feststellbar. 2) Kognitive Funktionen: signifiante Effekte in GN und in RG zu Gunsten von INT konnten bezüglich der Geschwindigkeit der Informationsverarbeitung und der Aufmerksamkeit gegenüber TAU nachgewiesen werden. 3) Soziale Funktionen: INT erzielte in GN und in RG eine signifikante Überlegenheit im psychsozialen Funktionsniveau (Generalisierungeffekt). Kognitive Remediationstherapie reduziert ausgeprägte Negativsymptome, unterstützt die Rückfallprophylaxe und verbessert kognitive und soziale Funktionen auch bei Patienten mit Negativsymptomen.

Efectos de la terapia asistida con animales en dominios cognitivos en pacientes con esquizofrenia

Esta investigación tiene como objetivo determinar la efectividad de incorporar un programa de terapia asistida con animales (TAA) al tratamiento farmacológico y programa individualizado de rehabilitación psicosociolaboral en pacientes con esquizofrenia que acuden a recursos de atención social de la red de atención pública de la Comunidad de Madrid. Hay dos momentos, un primer estudio en el que la investigación se centra en evaluar la mejora de dominios clínicos, psicosociales y cognitivos y un segundo estudio en el que la evaluación se centra en comprobar la mejora en dominios cognitivos utilizando una prueba específica de evaluación de procesos cognitivos en pacientes con esquizofrenia (MATRICS). Se plantean dos hipótesis en la medida en que se han realizado dos estudios. En un primer estudio se plantea que los cambios en las puntuaciones de variables clínicas, psicosociales y cognitivas del grupo con TAA serán mayores y significativas entre evaluaciones pre y post y frente a las del grupo sin TAA. El segundo estudio se centra, casi exclusivamente, en que la mejora de los dominios cognitivos del grupo con TAA será mayor y significativa entre evaluaciones pre y post y frente a las del grupo sin TAA...

Efectividad de un programa de juego basado en realidad virtual para la mejora cognitiva en la esquizofrenia

Objetivo: Evaluar la efectividad de un programa de juego basado en la realidad virtual para la mejora de los dominios cognitivos en pacientes con esquizofrenia. Método: Ensayo clínico aleatorizado con 40 pacientes con esquizofrenia, 20 en el grupo experimental y 20 en el grupo control. El grupo experimental recibió 10 sesiones con Nintendo Wii® durante 5 semanas, 50 minutos/sesión, 2 días/semana, además del tratamiento convencional. El grupo control sólo recibió tratamiento convencional. Resultados: Se encontraron diferencias estadísticamente significativas de las puntuaciones T-Score entre la preevaluación y la postevaluación en el grupo experimental en cinco de los seis dominios cognitivos evaluados: velocidad de procesamiento (F = 12,04, p = 0,001), atención/vigilancia (F = 12,75, p = 0,001), memoria de trabajo (F = 18,86, p <0,01), aprendizaje verbal (F = 7,6, p = 0,009), y razonamiento y resolución de problemas (F = 11,08, p = 0,002). Conclusiones: La participación en intervenciones de realidad virtual dirigidas al entrenamiento cognitivo ofrece un gran potencial de ganancias significativas en los diferentes dominios cognitivos evaluados en pacientes con esquizofrenia.