Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study.

BACKGROUND: Impulse control disorders and dyskinesia are common and disabling complications of dopaminergic treatment in Parkinson's disease. They may coexist and are possibly related. The objectives of this study were to assess the frequency and severity of impulse control disorders in Parkinson's disease patients with dyskinesia. METHODS: The ALTHEA study enrolled 251 Parkinson's disease patients with various degrees of dyskinesia severity from 11 movement disorders centers in Italy. Each patient underwent a comprehensive assessment including Unified Dyskinesia Rating Scale and the Questionnaire for Impulsive Compulsive Disorders in Parkinson Disease-Rating Scale. RESULTS: There was an overall 55% frequency of impulse control disorder and related behaviors (36% were clinically significant). The positive patients were younger at disease diagnosis and onset and had higher Unified Dyskinesia Rating Scale historical and total score (P = 0.001 and P = 0.02, respectively, vs negative). There was an increased frequency of clinically significant impulse control disorders in patients with severe dyskinesia (P = 0.013), a positive correlation between the questionnaire total score and dopamine agonist dose (P = 0.018), and a trend with levodopa dose. CONCLUSIONS: More than half of Parkinson's disease patients with dyskinesia have impulse control disorders and related behaviors, which are frequently clinically significant. Dopaminergic therapy total dose is associated with their severity. Clinicians should carefully assess patients with maladaptive behaviors and dyskinesia because they do not properly evaluate their motor and nonmotor status. © 2017 International Parkinson and Movement Disorder Society.

Predictors of Nursing Home Placement in a Cohort of European People with Alzheimer's Disease and Other Dementia Cases Enrolled in SCU-B or Non SCU-B Centers: The RECage Study.

Background: Nursing home placement (NHP) can be the final step of patients with Alzheimer's disease. Objective: We aimed to identify NHP predictors among 508 people with dementia with a 3-year follow-up. Methods: We analyzed data from the international observational RECage study, involving 508 people with especially Alzheimer's disease and comparing a cohort enrolled by five centers with a Special Care Unit for BPSD (behavioral and psychological symptoms of dementia) and another one enrolled by six centers lacking this facility. The tertiary objective of the study was to assess the possible role of the SCU-B in delaying NHP. We assessed the relationship of the baseline characteristics with NHP by means of univariate analysis followed by Cox's multivariate model. Results: Patients' mean age was 78.1 years, 54.9% were women. Diagnosis mean age was 75.4 (±8.32) years; the main diagnosis was Alzheimer's disease (296; 58.4%). During follow-up, 96 (18.9%) patients died and 153 (30.1%) were institutionalized without a statistically significant difference between the two cohorts (p = 0.9626). The mean NHP time was 902 (95% CI: 870-934). The multivariable analysis without death as a competing risk retained four independent predictors of NHP: age increase (hazard ratio (HR) = 1.023, 95% CI: 1.000-1.046), patient education level increase (HR = 1.062, 95% CI: 1.024-1.101), Neuropsychiatric Inventory total increase (HR = 1.018; 95% CI: 1.011-1.026), and total Mini-Mental State Examination as a favorable factor (HR = 0.948, 95% CI: 0.925-0.971). Gender (females versus males: HR = 1.265, 95% CI: 0.899-1.781) was included in the final Cox's model for adjusting the estimates for. Conclusions: Our data partially agree with the predictors of NHP in literature including the effect of high education level. No caregivers' factors were statistically significant. Clinical trial registration: NCT03507504.

Respectful Caring for the Agitated Elderly (ReCAGE): A Multicentre, Prospective, Observational Study to Evaluate the Effectiveness of Special Care Units for People with Dementia.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) bring complexity in the clinical management of people with dementia; therefore, it is important to evaluate different models of care, such as Special Care Units (SCU-B).∥Objective:To evaluate the SCU-B effectiveness toward alleviating BPSD and improving the quality of life (QoL) of patients and their caregivers.∥Methods:ReCAGE was a multicenter, controlled, longitudinal study where 508 patients with BPSD were enrolled in two cohorts: 262 patients from centers endowed with a SCU-B, and 246 from centers without SCU-B. Statistical analyses included factorial ANCOVA for comparison among centers. The primary endpoint was effectiveness of the SCU-B, measured through the Neuropsychiatric Inventory (NPI) changes. Secondary endpoints were change in QoL of patients and caregivers, and the tertiary endpoint was time to nursing home admission.∥Results:The NPI scores decreased in both arms, with a statistically significant difference from baseline to 36 months (p < 0.0001) in both cohorts. Over time, NPI decreased more steeply during the first year in the SCU-B arm, but in the following two years the slope was clearly in favor of the control arm. This different pattern of the two cohorts reached statistical significance at the interaction "cohort by time" (p < 0.0001). Conflicting results were found regarding the outcomes of quality of life, while there were no differences in time to institutionalization in both cohorts.∥Conclusion:The RECage study did not confirm the long-term superiority of the pathway comprising a SCU-B. A post-hoc analysis revealed data supporting their acute effectiveness during behavioral crises.

A Confirmatory and an Exploratory Factor Analysis of the Cohen-Mansfield Agitation Inventory (CMAI) in a European Case Series of Patients with Dementia: Results from the RECage Study.

BACKGROUND: One of the most widely used instruments for assessing agitation in dementia patients is the Cohen-Mansfield Agitation Inventory (CMAI), nevertheless no global score has been proposed. The aim of this study is: (a) to conduct a confirmatory (CFA) and exploratory factor analysis (EFA) of CMAI on people with dementia and Psychological and Behavioral Symptoms (BPSD), and (b) to propose an alternative structure, based on clinical criteria including all CMAI items. METHODS: Confirmatory and exploratory factor analyses were carried out on the CMAI 29 items administered at baseline to 505 patients with dementia (PwD) and BPSD enrolled in the international observational RECage study. RESULTS: The three-factor structure has not been confirmed by the CFA, whilst the EFA was carried out respectively on 25 items disregarding 4 items with a prevalence ≤5% and then on 20 items disregarding 9 items with a prevalence ≤10%. The four-factor structure explaining 56% of the variance comprised Physically Aggressive behavior, Verbally Aggressive behavior, Physically non-aggressive behavior, and Physically and verbally aggressive behavior. CONCLUSIONS: A new grouping of all items according to a clinical criterion is proposed, allowing for a more sensible evaluation of the symptoms leading to better differentiation.

Possible Contexts of Use for In Silico Trials Methodologies: A Consensus-Based Review.

The term "In Silico Trial" indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process. As In Silico Trials are a disruptively innovative class of new methodologies, it is important to have a list of possible CoUs highlighting potential applications for the development of the relative regulatory science. This review paper presents the result of a consensus process that took place in the InSilicoWorld Community of Practice, an online forum for experts in in silico medicine. The experts involved identified 46 descriptions of possible CoUs which were organised into a candidate taxonomy of nine CoU categories. Examples of 31 CoUs were identified in the available literature; the remaining 15 should, for now, be considered speculative.