KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia.

OBJECTIVE: Tardive dyskinesia is a persistent movement disorder induced by dopamine receptor blockers, including antipsychotics. Valbenazine (NBI-98854) is a novel, highly selective vesicular monoamine transporter 2 inhibitor that demonstrated favorable efficacy and tolerability in the treatment of tardive dyskinesia in phase 2 studies. This phase 3 study further evaluated the efficacy, safety, and tolerability of valbenazine as a treatment for tardive dyskinesia. METHOD: This 6-week, randomized, double-blind, placebo-controlled trial included patients with schizophrenia, schizoaffective disorder, or a mood disorder who had moderate or severe tardive dyskinesia. Participants were randomly assigned in a 1:1:1 ratio to once-daily placebo, valbenazine at 40 mg/day, or valbenazine at 80 mg/day. The primary efficacy endpoint was change from baseline to week 6 in the 80 mg/day group compared with the placebo group on the Abnormal Involuntary Movement Scale (AIMS) dyskinesia score (items 1-7), as assessed by blinded central AIMS video raters. Safety assessments included adverse event monitoring, laboratory tests, ECG, and psychiatric measures. RESULTS: The intent-to-treat population included 225 participants, of whom 205 completed the study. Approximately 65% of participants had schizophrenia or schizoaffective disorder, and 85.5% were receiving concomitant antipsychotics. Least squares mean change from baseline to week 6 in AIMS dyskinesia score was -3.2 for the 80 mg/day group, compared with -0.1 for the placebo group, a significant difference. AIMS dyskinesia score was also reduced in the 40 mg/day group (-1.9 compared with -0.1). The incidence of adverse events was consistent with previous studies. CONCLUSIONS: Once-daily valbenazine significantly improved tardive dyskinesia in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder. Valbenazine was generally well tolerated, and psychiatric status remained stable. Longer trials are necessary to understand the long-term effects of valbenazine in patients with tardive dyskinesia.

Big Data Challenges in Climate Science.

The knowledge we gain from research in climate science depends on the generation, dissemination, and analysis of high-quality data. This work comprises technical practice as well as social practice, both of which are distinguished by their massive scale and global reach. As a result, the amount of data involved in climate research is growing at an unprecedented rate. Climate model intercomparison (CMIP) experiments, the integration of observational data and climate reanalysis data with climate model outputs, as seen in the Obs4MIPs, Ana4MIPs, and CREATE-IP activities, and the collaborative work of the Intergovernmental Panel on Climate Change (IPCC) provide examples of the types of activities that increasingly require an improved cyberinfrastructure for dealing with large amounts of critical scientific data. This paper provides an overview of some of climate science's big data problems and the technical solutions being developed to advance data publication, climate analytics as a service, and interoperability within the Earth System Grid Federation (ESGF), the primary cyberinfrastructure currently supporting global climate research activities.

The relationship between trauma and clinical outcome variables among older adults with schizophrenia spectrum disorders.

OBJECTIVE: Stressful and traumatic life events have been implicated in the etiology and persistence of symptoms in schizophrenia, but little is known about their impact in later life. This article contrasts lifetime trauma among older persons with schizophrenia with their age peers in the general population, and examines whether greater trauma is associated with higher rates of nonremission of positive and negative symptoms, depression, or anxiety symptoms in the schizophrenia group. METHODS: The schizophrenia group consisted of 198 community-dwelling persons age 55 and older who developed a schizophrenia spectrum disorder before age 45. A community comparison group (N = 113) was recruited using randomly selected block-groups. Using the Trauma and Victimization Scale, the frequency × severity of lifetime traumatic events scores were calculated. In the schizophrenia group, subjects were dichotomized into low and high trauma groups. RESULTS: As compared to the community group, the schizophrenia group scored significantly higher on the total score and on 6 of 11 items of the Trauma and Victimization Scale. The schizophrenia group had significantly more traumatic events before age 17. In logistic regression analysis, a high level of trauma accumulated across the lifespan in the schizophrenia group was associated only with non-remission of positive symptoms; however, the persistence of positive symptoms was not associated with a traumatic event prior to age 17. CONCLUSION: Early trauma may play some role in the development of schizophrenia, but it does not seem to have any special role in the persistence of positive symptoms in later life. Rather, accumulated stressors may be more relevant clinically. The findings suggest that it may be profitable to consider therapies that reduce the psychological impact of traumatic events.

Successful aging in older adults with schizophrenia: prevalence and associated factors.

OBJECTIVE: This study contrasts the prevalence of successful aging in older adults with schizophrenia with their age peers in the community and examines variables associated with successful aging in the schizophrenia group. METHODS: The schizophrenia group consisted of 198 community-dwelling persons aged 55 years and older who developed schizophrenia before the age of 45 years. A community comparison group (N = 113) was recruited using randomly selected block groups. The three objective criteria proposed by Rowe and Kahn were operationalized using a six-item summed score. The association of 16 predictor variables with the successful aging score in the schizophrenia group was examined. RESULTS: The community group had significantly higher successful aging scores than the schizophrenia group (4.3 versus 3.0; t = 8.36, df = 309, p <0.001). Nineteen percent of the community group met all six criteria on the successful aging score versus 2% of the schizophrenia group. In regression analysis, only two variables-fewer negative symptoms and a higher quality of life index-were associated with the successful aging score within the schizophrenia group. CONCLUSION: Older adults with schizophrenia rarely achieve successful aging and do so much less commonly than their age peers. Only two significant variables were associated with successful aging neither of which are easily remediable. The elements that comprise the components of successful aging, especially physical health, may be better targets for intervention.

Outcome among community dwelling older adults with schizophrenia: results using five conceptual models.

There have been few studies examining the outcome of schizophrenia in later life. Using five conceptual models, we test two hypotheses with respect to range of outcomes among older schizophrenia outpatients and how they compare to their age peers in the community. We operationalized five outcome measures from the following conceptual models: Remission, adapting criteria of Andreasen et al. (The American Journal of Psychiatry, 162:441-449, 2005); Recovery, adapting the criteria by Liberman et al. (International Review of Psychiatry, 14:256-272, 2002); Community Integration using the model of Wong and Solomon (Mental Health Services Research, 4:13-28, 2002); Subjective and Objective Successful Aging using the model of Rowe and Kahn (Science, 237:143-149, 1987). The schizophrenia (S) group consisted of 198 community-dwelling persons aged 55 and over who developed schizophrenia before age 45 and a community comparison (CC) group (N = 113). Remission and recovery criteria were met by 49 and 17% of the S group, respectively. There were significant differences between the S and CC groups in the distribution of community integration and successful aging scales: 41% of the CC group met at least 10 of 12 criteria versus 23% of the S group on the Community Integration Scale; 19% of the CC group met all six criteria vs. 2% of the S group on the Objective Successful Aging Scale; 27% of the CC group vs. 13% of the S group met all six criteria on the Subjective Successful Aging Scale. Correlations among the five outcome measures ranged from r = .19 to .48 (median value: r = .26 or 7% shared variance). There is wide variability in outcome in later life depending on which measure is used. Rather than one universal indicator, each measure offers a different perspective that can provide useful guidelines for researchers, clinicians, and policy makers.

Symptomatic remission in a multiracial urban population of older adults with schizophrenia.

OBJECTIVE: Symptomatic remission has been reported in younger patients with schizophrenia. This study aims to determine the prevalence of symptomatic remission in older adults with schizophrenia. METHODS: The Schizophrenia Group consisted of 198 persons aged 55+ years living in the community who developed schizophrenia before age 45 years. Our definition of remission was adapted from the criteria of the Remission in Schizophrenia Working Group. To attain remission, persons had to have scores of <3 on eight domains of the Positive and Negative Symptom Scale and no hospitalizations within the previous year. Using George's Social Antecedent Model, we examined the association of remission with 18 predictor variables. RESULTS: Forty-nine percent of the sample met the criteria for symptomatic remission. In logistic regression analysis, four variables--fewer total network contacts, greater proportion of intimates, fewer lifetime traumatic events, and higher Dementia Rating Scale scores--were significantly associated with remission. CONCLUSIONS: Remission rates were consistent with those reported in younger samples. Our findings suggest that symptomatic remission is an attainable goal and that treatments focused on those variables associated with remission may augment outcomes in older persons with schizophrenia.

An object lesson: source determines the relations that trait anxiety, prostate cancer worry, and screening fear hold with prostate screening frequency.

Fears regarding prostate cancer and the associated screening are widespread. However, the relations between anxiety, cancer worry, and screening fear and screening behavior are complex, because anxieties stemming from different sources have different effects on behavior. In differentiating among anxieties from different sources (trait anxiety, cancer worry, and screening fear), we expected that cancer worry would be associated with more frequent screening, whereas fear of screening would be associated with less frequent screening. Hypotheses were tested in a sample of 533 men (ages 45-70 years) recruited using a stratified cluster-sampling plan. Men provided information on demographic and structural variables (age, education, income, marital status, physician discussion of risk and screening, access, and insurance) and completed a set of anxiety measures (trait anxiety, cancer worry, and screening fear). As expected, two-step multiple regressions controlling for demographics, health insurance status, physician discussion, and health-care system barriers showed that prostate-specific antigen and digital rectal examination frequencies had unique associations with cancer worry and screening fear. Specifically, whereas cancer worry was associated with more frequent screening, fear of screening was associated with less frequent screening at least for digital rectal examination; trait anxiety was inconsistently related to screening. Data are discussed in terms of their implications for male screening and the understanding of how anxiety motivates health behaviors. It is suggested that understanding the source of anxiety and the manner in which health behaviors such as cancer screenings may enhance or reduce felt anxiety is a likely key to understanding the associations between anxiety and behavioral outcomes.

Depression in older adults with schizophrenia spectrum disorders: prevalence and associated factors.

RATIONALE: Although depression is common in older adults with schizophrenia, it has not been well studied. The authors examine those factors that are related to depression in a multiracial urban sample of older persons with schizophrenia. METHODS: The schizophrenia group consisted of 198 persons aged 55 or older who lived in the community and developed schizophrenia before age 45. Persons with substantial cognitive impairment were excluded from the study. A community comparison group (N = 113) was recruited using randomly selected census tract data. The authors adapted George's Social Antecedent Model of Depression, which consists of six categories comprising 16 independent variables, and used a dichotomous dependent variable based on a Center for Epidemiologic Studies Depression Scale cutoff score of > or = 16. RESULTS: The schizophrenia group had significantly more persons with clinical depression than the community comparison group (32% versus 11%, respectively; chi(2) = 28.23, df = 1, p = 0.001). Bivariate analysis revealed that eight of the 16 variables were significantly related to clinical depression in the schizophrenia group. In logistic regression, six variables retained significance: physical illness (odds ratio [OR] = 1.60, 95% confidence interval [CI], 1.17-2.18), quality of life (OR = 0.84, 95% CI, 0.76-0.93), presence of positive symptoms (OR = 1.12, 95% CI, 1.02-1.21), proportion of confidants (OR = 0.03, 95% CI, 0.01-0.39), copes by using medications (OR = 2.12, 95% CI, 1.08-4.13), and copes with conflicts by keeping calm (OR = 1.34, 95% CI, 1.03-1.74). CONCLUSION: Consistent with earlier studies of schizophrenia in older persons, the authors found physical health, positive symptoms, and several nonclinical variables to be associated with depression. Potential points for intervention include strengthening social supports, improving physical well-being, more aggressive treatment of positive symptoms, and increasing the recognition and treatment of depression.

Factors affecting quality of life in a multiracial sample of older persons with schizophrenia.

OBJECTIVE: There have been few studies of quality of life (QOL) among older persons with schizophrenia. The authors used an adaptation of Lehman's QOL model to examine factors that impact QOL in a multiracial urban sample of older persons with schizophrenia. METHODS: The schizophrenia group consisted of 198 community-dwelling persons aged 55 years and older who developed schizophrenia before age 45 years. A community comparison group (N = 113) was recruited using randomly selected block-groups. The QOL model consisted of four variable sets (demographic, objective, clinical, and subjective) comprising 19 independent variables. The dependent variable was the Quality of Life Index (QLI). RESULTS: The schizophrenia group had a significantly lower QLI score than the comparison group (21.7 versus 24.2; t = -5.36, df = 362, p = 0.001). Within the schizophrenia group, in bivariate analyses, 11 of 19 variables were significantly related to QLI. In regression analysis, six variables were significantly associated with the QLI: fewer depressive symptoms, more cognitive deficits, fewer acute life stressors, fewer medication side effects, lower financial strain, and better self-rated health. The model explained 55% of the variance in QLI, with the demographic, objective, psychiatric illness, and subjective variable sets accounting for 6%, 35%, 9%, and 5% of the variance, respectively. With the exception of the demographic set, each of the variable sets added significant variance. CONCLUSION: Our data confirmed earlier reports that older persons with schizophrenia have lower self-reported quality of life than their age-matched peers. Our findings suggest that the factors impacting on QOL are potentially ameliorable and therefore provide an opportunity to enhance the well-being of this population.

Assessing quality of life in older persons with schizophrenia.

OBJECTIVE: There have been few studies of quality of life (QOL) indicators in older schizophrenic persons, and these studies have used narrow measures of QOL. The authors sought to demonstrate that self-appraisals of QOL are useful and valid in older schizophrenic persons. A second aim was to provide provisional support for a model of QOL in this population. METHODS: The sample was 99 community-dwelling schizophrenic persons age 55+ and a community-comparison group (N=84). Using the Quality of Life Index (QLI), they compared the variable sets of their model (Objective, Subjective, and Psychiatric domains) for the schizophrenic and the community samples to determine whether the explained variance in the QLI was equivalent between groups for each of the three variable sets. To assess the model of QOL, for the entire sample, the global scale score of the QLI was regressed on three predictor variable sets, the three demographic covariates, and group membership. RESULTS: All of the group differences were considered "small effect sizes." There were no significant differences between groups in the individual-variable regression coefficients. For the entire sample, when the QLI was regressed on the three predictor variable sets simultaneously, the model explained 61% of the variance in the QLI, and group membership was not significant. CONCLUSIONS: The analyses demonstrated the reliability and validity of the QLI in older schizophrenic persons and supported its validity by producing results comparable to general-community residents. The overall model was highly significant and should serve as basis for future studies of QOL.