Impact of Anticholinergic and Dopamine Receptor Blocking Drug Exposure on Parkinson Disease Trajectory and Outcomes

抗胆碱能药物和多巴胺受体阻断药物暴露对帕金森病轨迹和结果的影响

基本信息

批准号：
10018115
负责人：
Allison Willis
金额：
$ 53.05万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018115
关键词：
Accidental Injury Acute Address Adverse effects Affect Age Anti-Cholinergics Antipsychotic Agents Benchmarking Cessation of life Clinical Clinical Research Clinical Trials Clinical Trials Design Cognition Cohort Studies Data Data Analyses Data Collection Delirium Delusions Dementia Diagnosis Disease Disease Marker Disease Progression Dopamine Receptor Drug Exposure Dysautonomias Elderly Emergency Care Epidemiology Event Fall prevention Functional disorder Futility Future Gait General Population Genitourinary system Goals Guidelines Hallucinations Health Health Services Hip Fractures Hospitalization Hospitals Impaired cognition Impairment Individual Institutionalization Knowledge Life Expectancy Longitudinal cohort study Masks Measurement Medical Medicare Mental Depression Morbidity - disease rate National Institute of Neurological Disorders and Stroke Neurodegenerative Disorders Neurology Neuroprotective Agents Newly Diagnosed Nursing Homes Outcome Outcome Study Overactive Bladder Parkinson Disease Parkinson&apos s Dementia Paroxetine Pathway interactions Patients Pharmaceutical Preparations Pharmacology Pharmacotherapy Policies Population Prevention Psychotic Disorders Public Health Quality Indicator Quality of Care Randomized Recommendation Research Research Personnel Risk Risk Factors Safety Spasm Syndrome Testing Therapeutic Translating Variant acute care associated symptom burden of illness care outcomes cholinergic clinical center clinically significant cognitive testing cohort comparative design disability evidence base evidence based guidelines falls gastrointestinal health care service utilization health service use human old age (65+)improved improved outcome insight mortality motor symptom nervous system disorder next generation oxybutynin performance tests prospective quetiapine service intervention translational impact trend

项目摘要

Project Summary/Abstract Cognitive impairment and falls leading to hip fracture are leading causes of institutionalization and mortality in Parkinson disease (PD), a neurological disorder which predominantly affects the most rapidly growing segment of the U.S. population (older adults). Preventing falls or delaying the onset of dementia in PD would have a substantial public health impact. Drugs with anticholinergic (ACH) effects or dopamine receptor blocking (DRB) activity have been demonstrated to impair gait, cause cognitive dysfunction, hasten the progression of dementia and increase mortality. Parkinson disease patients are particularly vulnerable to adverse effects of ACH and DRB drugs due to PD-related disruption of central dopaminergic and cholinergic pathways. Furthermore, PD pharmacotherapy trials use gait and cognition as markers of disease progression without considering ACH or DRB burden. Yet, no clinical guidelines limiting the use of ACH or DRB drugs exist, representing a fundamental gap in knowledge this revised proposal will address. We plan to use Medicare prescription, clinical, and utilization data and rich clinical research data from a longitudinal cohort study of individuals with PD to identify the pharmacological determinants of preventable adverse health outcomes and unreliable clinical trial endpoints in PD. This study will 1) produce highly useful benchmark data on variation in prescribing in PD and 2) address a crucial clinical issue—comparative safety among therapeutic alternatives for medications with ACH and DRB potential in PD. We expect to fundamentally advance the field of clinical neurology by providing a strong evidence base for clinical guidelines and care quality indicators related to ACH and DRB burden in PD. Our results will also have a positive translational impact because defining the impact of ACH drugs on research measurements of disease trajectory and clinical outcomes will alter data collection and analysis strategies for future PD neuroprotective drug trials, improving the ability of such trials to identify effective drugs. We also directly address a priority recommendation from the 2014 NINDS Parkinson's Disease Research Agenda: `to determine factors that facilitate health services interventions'- by combining qualitative and quantitative data to produce new insights into potentially preventable outcomes in PD that directly translate into policy initiatives.

项目概要/摘要认知障碍和跌倒导致髋部骨折是住院和死亡的主要原因帕金森病 (PD) 是一种神经系统疾病，主要影响生长最快的神经系统预防跌倒或延缓帕金森症痴呆的发作将是美国人口中的一部分。具有抗胆碱能 (ACH) 作用或多巴胺受体的药物具有重大的公共健康影响。阻断（DRB）活动已被证明会损害步态，导致认知功能障碍，加速痴呆症的进展和死亡率的增加帕金森病患者特别容易受到影响。 ACH 和 DRB 药物因 PD 相关的中枢多巴胺能和胆碱能破坏而产生的不良反应此外，PD 药物治疗试验使用步态和认知作为疾病进展的标志。不考虑 ACH 或 DRB 负担然而，没有临床指南限制 ACH 或 DRB 药物的使用。存在，这代表了本修订提案将解决的知识方面的根本差距。我们计划使用来自医疗保险处方、临床和使用数据以及丰富的临床研究数据对帕金森病患者进行纵向队列研究，以确定可预防的药物决定因素 PD 的不良健康结果和不可靠的临床试验终点本研究将 1) 产生非常有用的结果。关于 PD 处方变化的基准数据，2) 解决一个关键的临床问题——比较安全性我们期望在帕金森病中具有 ACH 和 DRB 潜力的药物治疗替代方案中。通过为临床指南提供强有力的证据基础，从根本上推动临床神经病学领域的发展与 ACH 和 DRB 负担相关的护理质量指标我们的结果也将产生积极的结果。转化影响，因为定义了 ACH 药物对疾病轨迹研究测量的影响临床结果将改变未来 PD 神经保护药物试验的数据收集和分析策略，提高此类试验识别有效药物的能力我们还直接解决了一个优先事项。 2014 年 NINDS 帕金森病研究议程的建议：“确定影响因素促进卫生服务干预——通过结合定性和定量数据产生新的见解转化为PD中潜在可预防的结果，并直接转化为政策举措。