A good practice guide for translating and adapting hearing-related questionnaires for different languages and cultures.

OBJECTIVES: To raise awareness and propose a good practice guide for translating and adapting any hearing-related questionnaire to be used for comparisons across populations divided by language or culture, and to encourage investigators to publish detailed steps. DESIGN: From a synthesis of existing guidelines, we propose important considerations for getting started, followed by six early steps: (1) Preparation, (2, 3) Translation steps, (4) Committee Review, (5) Field testing and (6) Reviewing and finalising the translation. STUDY SAMPLE: Not applicable. RESULTS: Across these six steps, 22 different items are specified for creating a questionnaire that promotes equivalence to the original by accounting for any cultural differences. Published examples illustrate how these steps have been implemented and reported, with shared experiences from the authors, members of the International Collegium of Rehabilitative Audiology and TINnitus research NETwork. CONCLUSIONS: A checklist of the preferred reporting items is included to help researchers and clinicians make informed choices about conducting or omitting any items. We also recommend using the checklist to document these decisions in any resulting report or publication. Following this step-by-step guide would promote quality assurance in multinational trials and outcome evaluations but, to confirm functional equivalence, large-scale evaluation of psychometric properties should follow.

Methods for Neuroscience Drug Development: Guidance on Standardization of the Process for Defining Clinical Outcome Strategies in Clinical Trials.

Neurosciences clinical trials continue to have notoriously high failure rates. Appropriate outcomes selection in early clinical trials is key to maximizing the likelihood of identifying new treatments in psychiatry and neurology. The field lacks good standards for designing outcome strategies, therefore The Outcomes Research Group was formed to develop and promote good practices in outcome selection. This article describes the first published guidance on the standardization of the process for clinical outcomes in neuroscience. A minimal step process is defined starting as early as possible, covering key activities for evidence generation in support of content validity, patient-centricity, validity requirements and considerations for regulatory acceptance. Feedback from expert members is provided, regarding the risks of shortening the process and examples supporting the recommended process are summarized. This methodology is now available to researchers in industry, academia or clinics aiming to implement consensus-based standard practices for clinical outcome selection, contributing to maximizing the efficiency of clinical research.

New approaches in psychiatric drug development.

Numerous novel neuroscience-based drug targets have been identified in recent years. However, it remains unclear how these targets relate to the expression of symptoms in central nervous system (CNS) disorders in general and psychiatric disorders in particular. To discuss this issue, a New Frontiers Meetings of European College of Neuropsychopharmacology (ECNP) was organized to address the challenges in translational neuroscience research that are impeding the effective development of new treatments. The main aim of this meeting was to discuss scientific insights, concepts and methodologies in order to improve drug development for psychiatric disorders. The meeting was designed to bring together stakeholders from academia, pharmaceutical industry, and regulatory agencies. Here we provide a synopsis of the proceedings from the meeting entitled 'New approaches to psychiatric drug development'. New views on psychiatric drug development were presented to address the challenges and pitfalls as identified by the different stakeholders. The general conclusion of the meeting was that drug discovery could be stimulated by designing new classification and sensitive assessment tools for psychiatric disorders, which bear closer relationships to neuropharmacological and neuroscientific developments. This is in line with the vision of precision psychiatry in which patients are clustered, not merely on symptoms, but primarily on biological phenotypes that represent pathophysiological relevant and 'drugable' processes. To achieve these goals, a closer collaboration between all stakeholders in early stages of development is essential to define the research criteria together and to reach consensus on new quantitative biological methodologies and etiology-directed treatments.

EPICOG-SCH: A brief battery to screen cognitive impact of schizophrenia in stable outpatients.

Brief batteries in schizophrenia, are needed to screen for the cognitive impact of schizophrenia. We aimed to validate and co-norm the Epidemiological Study of Cognitive Impairment in Schizophrenia (EPICOG-SCH) derived brief cognitive battery. A cross-sectional outpatient evaluation was conducted of six-hundred-seventy-two patients recruited from 234 centers. The brief battery included well-known subtests available worldwide that cover cognitive domains related to functional outcomes: WAIS-III-Letter-Number-Sequencing-LNS, Category Fluency Test-CFT, Logical-Memory Immediate Recall-LM, and Digit-Symbol-Coding-DSC. CGI-SCH Severity and WHO-DAS-S were used to assess clinical severity and functional impairment, respectively. Unit Composite Score (UCS) and functional regression-weighted Composite Scores (FWCS) were obtained; discriminant properties of FWCS to identify patients with different levels of functional disability were analyzed using receiver-operating characteristic (ROC) technique. The battery showed good internal consistency, Cronbach's alpha = 0.78. The differences between cognitive performance across CGI-SCH severity level subscales ranged from 0.5 to 1 SD. Discriminant capacity of the battery in identifying patients with up to moderate disability levels showed fair discriminant accuracy with areas under the curve (AUC) > 0.70, p < 0.0001. An FWCS mean cut-off score ≥ 100 showed likelihood ratios (LR) up to 4.7, with an LR + of 2.3 and a LR - of 0.5. An FWCS cut-off ≥ 96 provided the best balance between sensitivity (0.74) and specificity (0.62). The EPICOG-SCH proved to be a useful brief tool to screen for the cognitive impact of schizophrenia, and its regression-weighted Composite Score was an efficient complement to clinical interviews for confirming patients' potential functional outcomes and can be useful for monitoring cognition during routine outpatient follow-up visits.

Cognitive Performance associated to functional outcomes in stable outpatients with schizophrenia.

BACKGROUND­OBJECTIVE: Prevalence data of cognitive impairment in Schizophrenia based on large population samples are scarce. Our goal is to relate cognition and functional outcomes, and estimate prevalence of cognitive impairment in a large sample of schizophrenia outpatients treated with second-generation antipsychotics. METHOD: A cross-sectional outpatient evaluation conducted during follow-up visits. Selection criteria included six-months stable treatment. The brief battery, EPICOG-SCH, covered four cognitive domains related to functional outcomes: working memory (WAIS-III-Letter-Number-Sequencing), executive function (Category Fluency Test; CFT), verbal memory (WMS-III-Logical-Memory), and information processing speed (Digit-Symbol-Coding and CFT). Clinical severity and functional impairment were assessed with CGI-SCH and WHO DAS-S. Impairment prevalence was calculated at ≤ 1.5 SD. RESULTS: Among patients recruited (n = 848) in 234 participating centers, 672 were under 6-month treatment. 61.5% (n = 413) reported cognitive impairment according to CGI-SCH Cognitive Subscale. Estimated prevalences were 85.9% (95% CI 85.6-86.2%) CFT-Fruits; 68.3% (95% CI 67.8-68.8%) CFT-Animals; 38.1% (95% CI 37.5-38.3%) Digit-Symbol-Coding; 24.8% (95% CI 24.1-25.5%) Verbal Memory-Units; 20.9% (95% CI 20.2-21.6%) Letter-Number Sequencing; 11.7% (95% CI 11.0-12.4%) Verbal Memory-Items. Negative and Depressive symptoms, Deficit Syndrome, and functional disability were related to poor performance. Functional disability was predicted by CGI-SCH-Overall severity (OR = 1.34635, p < 0.0001), CGI-SCH-Negative Symptoms (OR = 0.75540, p < 0.0001), working memory (Letter-Number-Sequencing) (OR = - 0.16442, p = 0.0004) and the time-course (OR = 0.05083, p = 0.0094), explaining 47% of the observed variability. CONCLUSION: Most prevalent impairments were on executive function and processing speed domains; however, working memory showed the strongest relationship to functional disability. Monitoring cognitive function during follow up is critical to understand patient's everyday functional capacity.

Subsyndromal Depressive Symptoms in Bipolar II Disorder: a Community Mental Health Services Cohort Study (SIN-DEPRES) / Síntomas depresivos subsintomáticos en trastorno bipolar II: un estudio de cohorte de servicios de salud comunitarios

Objectives: The aim of this study was to assess the prevalence and the impact of subclinical depressive symptoms (SDS) on the functional outcome of bipolar II (BD) outpatients in remission. Methods: Cross-sectional and prospective 16-week study of a cohort of 739 euthymic BD patients included by 94 investigators in Spain. Clinical stability was assessed at baseline and week 16 with the Clinical Global Impression scale for BD (CGI-BP-M), depressive symptoms at baseline with the Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Scale (MADRS) and the self-applied Center for Epidemiologic Studies-Depression Scale (CES-D). Functional status was evaluated with the Social and Occupational Functioning Assessment Scale (SOFAS) and Social Adaptation Self-evaluation Scale (SASS). Results: The sample of type II BD was composed by 202 patients. SDS were detected in 21.3% of patients (95% IC =15.9 to 27.6) at baseline. In apparently symptom-free patients, the incidence of SDS after 16 weeks was 29% (MADRS >7). At baseline, SDS patients compared to non-SDS presented poorer social-occupational performance (SOFAS mean difference -13.3, 95% CI from -17.1 to -9.5) and poorer social adjustment (SASS mean difference -4.3, 95% CI from -7.0 to -1.7). Depressive symptoms were inversely related to functional status and social adjustment: MADRS-SOFAS correlation coefficients r = -0.55 (p<0.0001) and MADRS-SASS correlation coefficients r = -0.43 (p<0.0001). The self-applied questionnaire identified additional cases with depressive symptoms at baseline, showing a SDS-Total prevalence of 51% identified by any method. A MADRS score 5 showed 0.75 sensitivity and 0.69 specificity in the detection of cases with possible SDS based on self-reported results as gold standard. Conclusions: Depressive symptoms in apparently remitted type II BD outpatients are common and as frequent as in other BD subtypes. These subclinical symptoms result in adverse occupational outcome and social maladjustment. MADRS and self-applied questionnaires during follow-up visits may provide important information about type II BD patients’ mood status and functionality.

Objetivos: Evaluar la prevalencia y el impacto de los síntomas depresivos subclínicos (SDS) en el resultado funcional de pacientes externos de bipolaridad II (TB) en remisión. Métodos: Estudio transversal y prospectivo, de 16 semanas de duración, de una cohorte de 739 pacientes eutímicos de TB incluidos por 94 investigadores en España. La estabilidad clínica se evaluó, en la línea base y en la semana 16, con la Escala Impresión Global Clínica para TB (CGI-BP-M); los síntomas depresivos, en la línea base, con la Escala de Calificación de la Depresión de Hamilton (HDRS), la Escala Montgomery-Asberg (MADRS) y la Escala Autoaplicada para la Depresión del Centro de Estudios Epidemiológicos (CES-D). El estado funcional se evaluó con la Escala de Evaluación del Funcionamiento Social y Ocupacional (SOFAS), y la Escala de Autoevaluación de la Adaptación Social (SASS). Resultados: La muestra de TB tipo II estuvo compuesta de 202 pacientes. Se detectaron SDS en 21,3% de los pacientes (95% IC = 15,9 a 27,6) en la línea base. En pacientes que aparentemente no presentaban síntomas, la incidencia de SDS después de 16 semanas era de un 29% (MADRS>7). En la línea base, los pacientes SDS, en comparación con los no SDS, demostraban un desempeño social-ocupacional más pobre (diferencia media SOFAS -13,3, 95% IC de -17,1 a -9,5) y un ajuste social más pobre (diferencia media SASS -4,3, 95% IC de -7,0 a -1,7). Los síntomas depresivos estaban relacionados inversamente con el estado funcional y el ajuste social: coeficientes de correlación MADRS-SOFAS r = -0,55 (p<0,0001) y coeficientes de correlación MADRS-SASS r = -0,43 (p<0,0001). El cuestionario autoaplicado identificó casos adicionales con síntomas depresivos en la línea base, y mostró una prevalencia total de SDS de 51% identificada por cualquier método. Un puntaje MADRS ≥ 5 mostró una sensibilidad de 0,75 y una especificidad de 0,69 en la detección de casos con posible SDS, basándose en los resultados autoreportados como el estándar de oro. Conclusiones: Los síntomas depresivos en pacientes externos de TB de tipo II aparentemente en remisión son comunes y son tan frecuentes como para los demás subtipos de TB. Estos síntomas subclínicos tienen resultados ocupacionales adversos así como inadaptación social. La MADRS y los cuestionarios autoaplicados durante las visitas de seguimiento pueden ofrecer información importante acerca del estado de ánimo y la funcionalidad del paciente de TB tipo II.