Comparison of Globus Pallidus Interna and Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease: An Institutional Experience and Review

Deep Brain Stimulation (DBS) has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi) and Subthalamic Nucleus (STN) are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patient\u27s profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institute\u27s DBS paradigm to ensure that patients receive the optimal therapy

How to Manage the Initiation of Apomorphine Therapy Without Antiemetic Pretreatment: A Review of the Literature

Introduction Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine. Methods To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD. Results Three studies were identified as providing relevant information on antiemetic prophylaxis with initiation of injectable apomorphine. The first study demonstrated that nausea was significantly more common in patients who received 3-days of trimethobenzamide pretreatment compared with those who did not, while the primary endpoint of second study found no significant effect on the binary incidence of nausea and/or vomiting on Day 1 of apomorphine treatment. In the third study, which used a slow titration scheme for apomorphine, transient nausea was reported in just 23.1% of the antiemetic nonusers. Conclusions Based on the reviewed trials and our clinical experience, we suggest that subcutaneous apomorphine therapy can be initiated using a slow titration scheme without antiemetic pretreatment

No Sex Differences in Use of Dopaminergic Medication in Early Parkinson Disease in the US and Canada - Baseline Findings of a Multicenter Trial

Background: Sex differences in Parkinson disease clinical features have been reported, but few studies have examined sex influences on use of dopaminergic medication in early Parkinson disease. The objective of this study was to test if there are differences in the type of dopaminergic medication used and levodopa equivalent daily dose between men and women with early Parkinson disease enrolled in a large multicenter study of Creatine as a potential disease modifying therapy – the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease Long-Term Study-1. Methods: Baseline data of 1,741 participants from 45 participating sites were analyzed. Participants from the United States and Canada were enrolled within five years of Parkinson Disease diagnosis. Two outcome variables were studied: type of dopaminergic medication used and levodopa equivalent daily dose at baseline in the Long-Term Study-1. Chi-square statistic and linear regression models were used for statistical analysis. Results: There were no statistically significant differences in the frequency of use of different types of dopaminergic medications at baseline between men and women with Parkinson Disease. A small but statistically significant difference was observed in the median unadjusted levodopa equivalent daily dose at baseline between women (300 mg) and men (325 mg), but this was not observed after controlling for disease duration (years since Parkinson disease diagnosis), disease severity (Unified Parkinson's Disease Rating Scale Motor and Activities of Daily Living Scores), and body weight. Conclusions: In this large multicenter study, we did not observe sex differences in the type and dose of dopaminergic medications used in early Parkinson Disease. Further research is needed to evaluate the influence of male or female sex on use of dopaminergic medication in mid- and late-stage Parkinson Disease

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood

Early mobilization and quality of life after stroke: findings from AVERT

Objective: To determine whether early and more frequent mobilization after stroke affects health-related quality of life. Methods: A Very Early Rehabilitation Trial (AVERT) was an international, multicenter (56 sites), phase 3 randomized controlled trial, spanning 2006–2015. People were included if they were aged ≥18 years, presented within 24 hours of a first or recurrent stroke (ischemic or hemorrhagic), and satisfied preordained physiologic criteria. Participants were randomized to usual care alone or very early and more frequent mobilization in addition to usual care. Quality of life at 12 months was a prespecified secondary outcome, evaluated using the Assessment of Quality of Life 4D (AQoL-4D). This utility-weighted scale has scores ranging from −0.04 (worse than death) to 1 (perfect health). Participants who died were assigned an AQoL-4D score of 0. Results: No significant difference in quality of life at 12 months between intervention (median 0.47, interquartile range [IQR] 0.07–0.81) and usual care (median 0.49, IQR 0.08–0.81) groups was identified (p = 0.86), nor were there any group differences across the 4 AQoL-4D domains. The same lack of group difference in quality of life was observed at 3 months. When cohort data were analyzed (both groups together), quality of life was strongly associated with acute length of stay, independence in activities of daily living, cognitive function, depressive symptoms, and anxiety symptoms (all p < 0.001). Quality of life in AVERT participants was substantially lower than population norms, and the gap increased with age. Conclusions: Earlier and more frequent mobilization after stroke did not influence quality of life

Have Anglo-Saxon concepts really influenced the development of European qualifications policy?

This paper considers how far Anglo-Saxon conceptions of have influenced European Union vocational education and training policy, especially given the disparate approaches to VET across Europe. Two dominant approaches can be identified: the dual system (exemplified by Germany); and output based models (exemplified by the NVQ ‘English style’). Within the EU itself, the design philosophy of the English output-based model proved in the first instance influential in attempts to develop tools to establish equivalence between vocational qualifications across Europe, resulting in the learning outcomes approach of the European Qualifications Framework, the credit-based model of European VET Credit System and the task-based construction of occupation profiles exemplified by European Skills, Competences and Occupations. The governance model for the English system is, however, predicated on employer demand for ‘skills’ and this does not fit well with the social partnership model encompassing knowledge, skills and competences that is dominant in northern Europe. These contrasting approaches have led to continual modifications to the tools, as these sought to harmonise and reconcile national VET requirements with the original design. A tension is evident in particular between national and regional approaches to vocational education and training, on the one hand, and the policy tools adopted to align European vocational education and training better with the demands of the labour market, including at sectoral level, on the other. This paper explores these tensions and considers the prospects for the successful operation of these tools, paying particular attention to the European Qualifications Framework, European VET Credit System and European Skills, Competences and Occupations tool and the relationships between them and drawing on studies of the construction and furniture industries

An anarchy of cultures: aesthetics and the changing school

It is the contention of this paper that schools are currently sandwiched between demands of the economy on one side and increasingly fundamentalist communities on the other; that schools need some degree of autonomy from each; that the greatest challenge of the century is how we can live together despite our differences; and that the only way of successfully meeting this challenge is for schools to put social justice at the heart of their activities, activities that are best informed by the cultivation of reasoned imagination – that is, by an aesthetic approach to the development of intellectual, social, cultural, economic and personal identities