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.

Sense of Well-Being in Patients with Fibromyalgia: Aerobic Exercise Program in a Mature Forest-A Pilot Study.

Background and Objective. Most patients with fibromyalgia benefit from different forms of physical exercise. Studies show that exercise can help restore the body's neurochemical balance and that it triggers a positive emotional state. So, regular exercise can help reduce anxiety, stress, and depression. The aim of this study was to analyze the benefits of moderate aerobic exercise when walking in two types of forests, young and mature, and to assess anxiety, sleep, pain, and well-being in patients with fibromyalgia. Secondary objectives included assessing (i) whether there were differences in temperature, sound, and moisture, (ii) whether there was an improvement in emotional control, and (iii) whether there was an improvement in health (reduction in pain) and in physical and mental relaxation. Patients and Methods. A study involving walking through two types of forests (mature and young) was performed. A total of 30 patients were randomly assigned to two groups, mature and young forests. The participants were administered the following tests: the Spanish version of the Revised Fibromyalgia Impact Questionnaire (FIQR) at baseline and the end-point of the study, the State-Trait Anxiety Inventory (STAI) after each walk, and a series of questions regarding symptomatic evolution. Several physiological parameters were registered. Results. FIQR baseline and end-point scores indicated a significant decrease in the symptomatic subscale of the FIQ (SD = 21.7; z = -2.4; p = 0.041). The within-group analysis revealed that differences were significant with respect to days of intense pain, insomnia, and days of well-being only in the group assigned to the mature forest, not in the group assigned to the young forest. No differences were found with respect to anxiety. Conclusions. Although the main aim of this research was not achieved, as the results revealed no differences between the groups in the two forest types, authors could confirm that an aerobic exercise program consisting of walking through a mature forest can provide the subjective perception of having less days of pain and insomnia and more days of wellness, in patients with fibromyalgia.

Sobrepeso y obesidad en preadolescentes mexicanos: estudio descriptivo, variables correlacionadas y directrices de prevención / Overweight and obesity in Mexican preadolescents: a descriptive study, correlated variables and prevention guidelines / Sobrepeso e obesidade em pré-adolescentes mexicanos: estudo descritivo, variáveis correlacionadas e diretrizes de prevenção

El sobrepeso y la obesidad representan serios problemas de salud pública. Se realizó un estudio descriptivo y correlacional de variables asociadas al sobrepeso y la obesidad en preadolescentes mexicanos escolarizados en México DF. Se valoró la Autoestima general (LAWSEQ, por sus siglas en inglés), Autoestima corporal (BES, por sus siglas en inglés), Actitudes hacia la alimentación (ChEAT, por sus siglas en iglés) e Imagen corporal (BIA, por sus siglas en inglés) y comparaciones por género y edad. La muestra fue de 600 alumnos, niños y niñas de entre nueve y doce años. Se encontró una baja autoestima general (más baja en las niñas y en los participantes de mayor edad) y corporal y una buena actitud hacia la alimentación. Los participantes se percibieron y creyeron ser vistos con sobrepeso y obesidad, pero a futuro e idealmente desearon figuras más delgadas. Se propone que los programas de prevención contemplen educación para la salud, actividad física, control de aspectos genéticos, actitudes funcionales (tendientes a una buena autoestima y actitudes positivas hacia la comida sana), e involucramiento de la familia y el entorno social.

Overweight and obesity are serious public health problems. A descriptive and correlational study of variables associated with overweight and obesity of Mexican school preadolescents in Mexico DF was performed. General self-esteem (LAWSEQ, for its English acronym), body esteem (BES, for its English acronym), Attitudes towards food (ChEAT, for its English acronym) and body image (BIA, for its English acronym) were assessed and comparisons by gender and age were drawn. The sample was formed by 600 students, boys and girls aged between nine and twelve. A general low self-esteem and body esteem (lower in girls and in older participants) as well as a good attitude toward eating were found. Participants perceived themselves and believed they were seen as overweight and obese but ideally they wanted thinner figures in the future. Prevention programs are proposed to include health education, physical activity, genetic control, functional attitudes (geared toward generating good self-esteem and positive attitudes toward healthy eating), as well as involvement of the family and social environment.

O sobrepeso e a obesidade representam sérios problemas de saúde pública. Realizou-se um estudo descritivo e correlacional de variáveis associadas ao sobrepeso e a obesidade em pré-adolescentes mexicanos escolarizados em México DF. Avaliou-se a Autoestima general (LAWSEQ, por suas siglas em inglês), Autoestima corporal (BES, por suas siglas em inglês), Atitudes com respeito à alimentação (ChEAT, por suas siglas em inglês) e Imagem corporal (BIA, por suas siglas em inglês) e comparações por gênero e idade. A amostra foi de 600 alunos, meninos e meninas entre nove e doze anos. Encontrou-se uma baixa autoestima geral (mais baixa nas meninas e nos participantes de maior idade ) e corporal e uma boa atitude com relação à alimentação. Os participantes se perceberam e acreditaram ser vistos com sobrepeso e obesidade, mas a futuro e idealmente desejaram figuras mais magras. Propõe-se que os programas de prevenção contemplem educação para a saúde, atividade física, controle de aspectos genéticos, atitudes funcionais (tendentes a uma boa autoestima e atitudes positivas com respeito à comida saudável), e envolvimento da família e do entorno social.

Burden associated with the presence of anosognosia in Alzheimer's disease.

OBJECTIVES: Anosognosia is the lack of deficit awareness, and it is a common symptom in patients with Alzheimer's disease (AD). The objective of this study was to assess the relationship between anosognosia and caregiver burden. METHODS: This was a cross-sectional, analytical study of patients who were diagnosed with AD and their caregivers. Anosognosia was evaluated using the Experimenter Rating Scale, and caregiver burden was evaluated using the Burden Interview (BI). Using the BI's comprehensive scoring and each of its five factors as dependent variables, we adjusted six linear regression models to determine the effect of anosognosia on caregiver burden. RESULTS: The sample consisted of 124 patients and 124 caregivers. The mean patient age was 78.9 years (SD = 6.9); the mean caregiver age was 59.7 years (SD = 13.6), and 66.6% of the caregivers were women. The prevalence of anosognosia was 24.2% (95% confidence interval = 16.7-33.3). The degree of caregiver burden was associated with the degree of anosognosia (r(2) = 0.426; standardised beta [ßs] = 0.346; p < 0.001), which explained 14.7% of the variance. For the BI factors, the Experimenter Rating Scale was associated with physical and social burden (r(2) = 0.452; ßs = 0.378; p < 0.001), relationship of dependence (r(2) = 0.301; ßs = 0.203; p = 0.010) and emotional stress (r(2) = 0.212; ßs = 0.227; p = 0.014). CONCLUSIONS: The presence of anosognosia in patients with AD is an independent factor that increases caregiver burden by increasing physical wear, social isolation, dependence and tension related to patient care.

Prevalence of frailty phenotypes and risk of mortality in a community-dwelling elderly cohort.

OBJECTIVES: to determine the prevalence of three independent, disability-free and operationally defined frailty phenotypes and the associated risk of mortality in a community-dwelling older people cohort over 74 years of age. METHODS: observational, prospective and population-based design. Bio-psycho-social variables were assessed using a range of standardised instruments. The physical frailty phenotype (PFP), mental frailty phenotype (MFP) and social frailty phenotype (SFP) were operationally defined using a deficit accumulation model that excluded disability. Logistic regression analyses explored associations of the frailty phenotypes with sex, age and marital status, and a Cox proportional hazard regression analysis was performed to evaluate the association between frailty phenotypes and mortality. RESULTS: of the eligible individuals, 82% (n = 875) participated. The prevalence of any frailty phenotype in an individual was 38.8%; 17.3% exhibited the PFP, 20.2% exhibited the MFP, and 8.9% exhibited the SPF. Older and female were more likely to exhibit the PFP, and widowhood was associated with the SFP. The hazard ratios of mortality were 3.09 (95% CI = 1.54-6.17) for the PFP and 2.69 (95% CI = 1.01-7.25) for the SFP. CONCLUSION: three different disability-free frailty phenotypes were differentially related to the socio-demographical characteristics of sex, age and marital status and independently predicted risk of mortality.

[Risk factors associated with eating disorders in Mexican preadolescents with normal weight]. / Factores de riesgo asociados a los trastornos de la conducta alimentaria en preadolescentes mexicanos con normopeso.

This study aimed to identify the differences in body self-esteem, general self-esteem and eating attitudes in a representative sample of children, aged 9-12 years, attending school in México DF. The logistic regression model incorporated the variables of sex, general self-esteem, BMI, age and discrepancy between the perceived image and the ideal image. Participants with an increased risk of eating disorders were girls: a) with less general self-esteem; b) BMI at the upper range of normal weight; c) greater negative discrepancy between perceived and ideal image; d) aged 11-12 years. Higher general self-esteem would act as a protector for eating disorders, while the desire for a thinner ideal body would be a risk factor.

Grouping and trajectories of neuropsychiatric symptoms in patients with Alzheimer's disease. Part II: two-year patient trajectories.

Behavioral and psychological symptoms of dementia (BPSD) are characterized by fluctuations in their frequency and severity as well as by differences in the concurrent presentation of different symptoms. The goal of the current study was to identify groups of patients with Alzheimer's disease (AD) that had similar trajectories in the expression of BPSD. Over a 24-month period, an observational study was conducted using a population of ambulatory patients with AD of mild or moderate severity. The Neuropsychiatric Inventory (NPI) was administered every 6 months to the patient's caregiver. To classify patients according to changes in the frequency and severity of BPSD, growth mixture models were fitted to the applied to the grouping of NPI subscales in the following three categories: psychotic syndrome (hallucinations and delusions), affective syndrome (depression, anxiety, irritability, and agitation), and behavioral syndrome (disinhibition, euphoria, apathy, and aberrant motor behavior). The sample population consisted of 491 patients (70.9% women) that had an average age of 75.2 years (SD=6.6). Different trajectory patterns were identified based on differences in changes over the time in the frequency (stable, increasing, decreasing, or fluctuating in course) and severity (low, moderate, or elevated severity) for psychotic syndrome, emotional syndrome, and behavior syndrome. Patients with AD display a high degree of variability in the evolutionary course of BPSD. It is possible to identify groups of patients with similar evolutionary trajectories in terms of changes in the frequency and severity of BPSD.

Grouping and trajectories of the neuropsychiatric symptoms in patients with Alzheimer's disease, part I: symptom clusters.

Behavioral and psychological symptoms of dementia (BPSD) are frequently observed in Alzheimer's disease (AD) and affect more than 80% of patients over the course of AD. The goal of this study was to establish a model for grouping the symptoms of BPSD into clinical syndromes. Over a 24-month period, an observational study was conducted using a population of ambulatory patients with AD of mild to moderate severity. The Neuropsychiatric Inventory (NPI) was administered to the patients' caregivers every 6 months. BPSD were grouped using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of the NPI scores of each assessment. The sample population consisted of 491 patients (70.9% women) with an average age of 75.2 years (SD=6.6). The five EFA suggested that there was a stable three-factor structure. According to the results of the EFA, three models of symptom grouping were adjusted using CFA methodology. The CFA model that satisfactorily grouped the NPI scores into three factors included a psychotic syndrome (hallucinations, delusions), an affective syndrome (depression, anxiety, irritability, agitation) and a behavior syndrome (euphoria, disinhibition, apathy, aberrant motor behavior). Based on our findings, we propose a model for grouping the BDSD in which there are core nuclear syndromes (psychotic and affective) as well as an unspecified behavior syndrome comprising satellite symptoms that may be related to the presence of the nuclear syndromes.

[Proposal for a consensus version of the Fibromyalgia Impact Questionnaire (FIQ) for the Spanish population]. / Propuesta de una versión de consenso del Fibromyalgia Impact Questionnaire (FIQ) para la población española.

OBJECTIVE: To obtain an updated FIQ consensus version for patients in Spain, the Cuestionario de Impacto de la Fibromialgia (CIF). MATERIAL AND METHODS: The CIF elaboration was carried out with the participation of all the groups of researchers in the 4 previous FIQ Spanish versions, and taking into account the recent updated version of the original FIQ. The CIF was completed by a sample of fibromialgia patients to explore how comprensible its items are and to compare its global score with 2 fibromialgia composite severity indexes, one semi-objective and one subjective. The corresponding Spearman correlation coefficients were determined RESULTS: The main modifications introduced in the questionnaire are shown. Some patients were confused in their responses to subitem "j" and item 3, but not with regard to the remaining items or subitems. Correlation coeficients between the CIF and the semi-objective and subjective fibromialgia severity indexes were 0.57 and 0.76 respectively (P<001). CONCLUSION: The CIF is proposed as an updated Spanish version of the FIQ.