Caregiver Burden in Late-Stage Parkinsonism and Its Associations

Background: Patients in the late stages of parkinsonism are highly dependent on others in their self-care and activities of daily living. However, few studies have assessed the physical, psychological and social consequences of caring for a person with late-stage parkinsonism. Patients and methods: Five hundred and six patients and their caregivers from the Care of Late Stage Parkinsonism (CLaSP) study were included. Patients’ motor and non-motor symptoms were assessed using the UPDRS and Non-motor symptom scale (NMSS), Neuropsychiatric inventory (NPI-12), and caregivers’ health status using the EQ-5D-3 L. Caregiver burden was assessed by the Zarit Burden Interview (ZBI). Results: The majority of caregivers were the spouse or life partner (71.2%), and were living with the patient at home (67%). Approximately half of caregivers reported anxiety/depression and pain/discomfort (45% and 59% respectively). The factors most strongly associated with caregiver burden were patients’ neuropsychiatric features on the total NPI score (r = 0.38, p < 0.0001), total NMSS score (r = 0.28, p < 0.0001), caring for male patients and patients living at home. Being the spouse, the hours per day assisting and supervising the patient as well as caregivers’ EQ-5D mood and pain scores were also associated with higher ZBI scores (all p < 0.001). Conclusion: The care of patients with late stage parkinsonism is associated with significant caregiver burden, particularly when patients manifest many neuropsychiatric and non-motor features and when caring for a male patient at home

The late stage of Parkinson's –results of a large multinational study on motor and non-motor complications

INTRODUCTION: There is little information on the late stages of parkinsonism. METHODS: We conducted a multicentre study in 692 patients with late stage parkinsonism in six European countries. Inclusion criteria were disease duration of ≥7 years and either Hoehn and Yahr stage ≥4 or Schwab and England score of 50 or less. RESULTS: Average disease duration was 15.4 (SD 7.7) years and mean total UPDRS score was 82.7 (SD 22.4). Dementia according to MDS-criteria was present in 37% of patients. Mean levodopa equivalence dose was 874.1 (SD 591.1) mg/d. Eighty two percent of patients reported falls, related to freezing (16%) or unrelated to freezing (21% of patients) or occurring both related and unrelated to freezing (45%), and were frequent in 26%. Moderate-severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16% and tremor by 11%. Off-periods occurred in 68% and were present at least 50% of the day in 13%, with morning dystonia occurring in 35%. Dyskinesias were reported by 45% but were moderate or severe only in 7%. Moderate-severe fatigue, constipation, urinary symptoms and nocturia, concentration and memory problems were encountered by more than half of participants. Hallucinations (44%) or delusions (25%) were present in 63% and were moderate-severe in 15%. The association with overall disability was strongest for severity of falls/postural instability, bradykinesia, cognitive score and speech impairment. CONCLUSION: These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients

Centrosome amplification mediates small extracellular vesicles secretion via lysosome disruption

PreprintSummary Bidirectional communication between cells and their surrounding environment is critical in both normal and pathological settings. Extracellular vesicles (EVs), which facilitate the horizontal transfer of molecules between cells, are recognized as an important constituent of cell-cell communication. In cancer, alterations in EV secretion contribute to the growth and metastasis of tumor cells. However, the mechanisms underlying these changes remain largely unknown. Here, we show that centrosome amplification is associated with and sufficient to promote small extracellular vesicle ( S EV) secretion in pancreatic cancer cells. This is a direct result due of lysosomal dysfunction, caused by increased reactive oxygen species (ROS) downstream of extra centrosomes. Defects in lysosome function promotes multivesicular body fusion with the plasma membrane, thereby enhancing S EV secretion. Furthermore, we find that S EVs secreted in response to amplified centrosomes are functionally distinct and activate pancreatic stellate cells (PSCs). These activated PSCs promote the invasion of pancreatic cancer cells in heterotypic 3-D cultures. We propose that S EVs secreted by cancer cells with amplified centrosomes influence the bidirectional communication between the tumor cells and the surrounding stroma to promote malignancy

Scale-free brain functional networks

Functional magnetic resonance imaging (fMRI) is used to extract {\em functional networks} connecting correlated human brain sites. Analysis of the resulting networks in different tasks shows that: (a) the distribution of functional connections, and the probability of finding a link vs. distance are both scale-free, (b) the characteristic path length is small and comparable with those of equivalent random networks, and (c) the clustering coefficient is orders of magnitude larger than those of equivalent random networks. All these properties, typical of scale-free small world networks, reflect important functional information about brain states.Comment: 4 pages, 5 figures, 2 table

An ERK1/2-driven RNA-binding switch in nucleolin drives ribosome biogenesis and pancreatic tumorigenesis downstream of RAS oncogene

Oncogenic RAS signaling reprograms gene expression through both transcriptional and post-transcriptional mechanisms. While transcriptional regulation downstream of RAS is relatively well characterized, how RAS post-transcriptionally modulates gene expression to promote malignancy remains largely unclear. Using quantitative RNA interactome capture analysis, we here reveal that oncogenic RAS signaling reshapes the RNA-bound proteomic landscape of pancreatic cancer cells, with a network of nuclear proteins centered around nucleolin displaying enhanced RNA-binding activity. We show that nucleolin is phosphorylated downstream of RAS, which increases its binding to pre-ribosomal RNA (rRNA), boosts rRNA production, and promotes ribosome biogenesis. This nucleolin-dependent enhancement of ribosome biogenesis is crucial for RAS-induced pancreatic cancer cell proliferation and can be targeted therapeutically to inhibit tumor growth. Our results reveal that oncogenic RAS signaling drives ribosome biogenesis by regulating the RNA-binding activity of nucleolin and highlight a crucial role for this mechanism in RAS-mediated tumorigenesis

Resource Utilization of Patients with Parkinson's Disease in the Late Stages of the Disease in Germany: Data from the CLaSP Study.

Objective: The Care of Late-Stage Parkinsonism (CLaSP) study aimed to collect qualitative and standardized patient data in six European countries (France, Germany, Netherlands, Portugal, UK, Sweden) to enable a detailed evaluation of the underexplored late stages of the disease (Hoehn and Yahr stage > 3) using clinical, neuropsychological, behavioral, and health economic data. The aim of this substudy was to provide a health economic evaluation for the German healthcare system. Methods: In Germany, 228 patients were included in the study. Costs were calculated from a societal perspective for a 3-month period. Univariate analyses were performed to identify cost-driving predictors. Total and direct costs were analyzed using a generalized linear model with a γ-distributed dependent variable and log link function. Indirect costs were analyzed using a binomial generalized linear model with probit link function. Results: The mean costs for the 3-month period were approximately €20,000. Informal care costs and hospitalization are approximately €11,000 and €5000. Direct costs amounted to 89% of the total costs, and the share of indirect costs was 11%. Independent predictors of total costs were the duration of the disease and age. The duration of the disease was the main independent predictor of direct costs, whereas age was an independent predictor of indirect costs. Discussion: Costs in the late stage of the disease are considerably higher than those found in earlier stages. Compared to the latter, the mean number of days in hospital and the need for care is increasing. Informal caregivers provide most of the care

Characteristics of Patients with Late-Stage Parkinsonism who are Nursing Home Residents Compared with those Living at Home

OBJECTIVES: To determine clinical characteristics and treatment complications of patients with late-stage Parkinsonism living in nursing homes compared with those living at home. DESIGN: Cross-sectional analysis. SETTING AND PARTICIPANTS: This study is an analysis of 692 patients with late stage Parkinsonism recruited to an in-depth international study, Care of Late-Stage Parkinsonism (CLaSP). MEASURES: Sociodemographic characteristics were compared between patients who were living in a nursing home (n = 194) and those living at home (n = 498). Clinical assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), the nonmotor symptom scale, the neuropsychiatric inventory, and a structured interview of patients and carers. Predictors of nursing home status were determined in a multivariate analysis. RESULTS: Nursing home placement was strongly associated with more severe cognitive impairment, worse UPDRS motor scores and disability, and with being unmarried and older. Although nursing home residents had significantly higher axial scores, falls were less common. Despite similar levodopa equivalence doses, they had less dyskinesia. Nonmotor symptom burden, particularly delusion, hallucination, and depression scores were higher in nursing home residents, and they were more frequently on psychotropic medication. They had lower rates of dopamine agonist use and lower rates of impulse control disorders. In multivariate analysis, being unmarried, presence of cognitive impairment, worse disease severity as assessed on the UPDRS parts II and III, severity of delusions, and lower rate of dyskinesia were associated with nursing home placement. CONCLUSIONS AND IMPLICATIONS: These clinical characteristics suggest that in patients with Parkinsonsim who are nursing home residents, presence of cognitive impairment and delusions particularly add to the higher overall symptom burden, and more often require specific treatments, including clozapine. Despite similar levodopa equivalent daily dose, motor severity is higher, and dyskinesias, indicative of a response to levodopa, are less common. Falls, however, also occur less commonly, and dopamine agonists are less frequently used, with lower rates of impulse control disorder

Engagement 2.0. Vom passiven Wahrnehmen zum aktiven Nutzen neuer Kommunikationstechnologien

Im vorliegenden Beitrag beschreiben die Autoren einen seit zwei Jahren am Bundesinstitut für Erwachsenenbildung situierten Kurs, der engagierte Menschen in die Kommunikationstechniken und -werkzeuge im sogenannten Web 2.0 einführt. Als "politische Kommunikation" betrachten sie alle öffentlichkeitswirksamen bzw. zielgruppenbezogenen Aktivitäten für Anliegen, die im Selbstbewusstsein der AkteurInnen als öffentlich, als Interessen der Allgemeinheit oder aber auch als moralische Ansprüche an die Gesellschaft verstanden werden. Den Abschluss des Beitrages bildet der Ausblick auf eine im Entstehen befindliche Webcommunity der AbsolventInnen des Kurses. (DIPF/Orig.)The authors of the present article describe a course at the Austrian Federal Institute of Adult Education (bifeb) that has introduced dedicated people to Web 2.0 communication technologies and tools for the last two years. For the authors, “political communication” represents all public-oriented and target group related activities surrounding matters that are considered to be public in the self-awareness of those involved, interests of the general public or also moral demands on society. The end of the article provides a panorama of the web community that is being created by the course graduates. (DIPF/Orig.

Digital Inclusion Across the Americas and Caribbean

This research brings together digital inequality scholars from across the Americas and Caribbean to examine efforts to tackle digital inequality in Uruguay, Chile, Peru, Brazil, Mexico, Cuba, Jamaica, the United States, and Canada. As the case studies show, governmental policy has an important role to play in reducing digital disparities, particularly for potential users in rural or remote areas, as well as populations with great economic disparities. We find that public policy can effectively reduce access gaps when it combines the trifecta of network, device, and skill provision, especially through educational institutions. We also note, that urban populations have benefitted from digital inclusion strategies to a greater degree. This underscores that, no matter the national context, rural-urban digital inequality (and often associated economic inequality) is resistant to change. Even when access is provided, potential users may not find it affordable, lack skills, and/or see no benefit in adoption. We see the greatest potential for future digital inclusion in two related approaches: 1) initiatives that connect with hard-to-reach, remote, and rural communities outside urban cores and 2) initiatives that learn from communities about how best to provide digital resources while respecting their diversely situated contexts, while meeting social, economic and political needs