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

• 批准号: 10225511
• 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
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225511
• 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' s Dementia; Paroxetine; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Policies; Population; Prevention; Psychoses; Public Health; Quality Indicator; Quality of Care; Randomized; Recommendation; Research; Research Personnel; Risk; Risk Factors; Spasm; Syndrome; Testing; Therapeutic; Translating; Variant; acute care; associated symptom; burden of illness; care outcomes; cholinergic; clinical center; clinically significant; cognitive testing; cohort; comparative safety; 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

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.

项目总结/文摘

项目成果

Patterns of Dementia Treatment and Frank Prescribing Errors in Older Adults With Parkinson Disease.

• DOI: 10.1001/jamaneurol.2018.2820
• 发表时间: 2019-01-01
• 期刊: JAMA neurology
• 影响因子: 29
• 作者: Mantri S;Fullard M;Gray SL;Weintraub D;Hubbard RA;Hennessy S;Willis AW
• 通讯作者: Willis AW

Using Medical Claims Analyses to Understand Interventions for Parkinson Patients.

• DOI: 10.3233/jpd-171277
• 发表时间: 2018
• 期刊: Journal of Parkinson's disease
• 作者: Bloem BR;Ypinga JHL;Willis A;Canning CG;Barker RA;Munneke M;De Vries NM
• 通讯作者: De Vries NM

β2-adrenoreceptor medications and risk of Parkinson disease.

• DOI: 10.1002/ana.25341
• 发表时间: 2018-11
• 期刊: Annals of neurology
• 影响因子: 11.2
• 作者: Searles Nielsen S;Gross A;Camacho-Soto A;Willis AW;Racette BA
• 通讯作者: Racette BA

Author response: Utilization of rehabilitation therapy services in Parkinson disease in the United States.

作者回应：美国帕金森病康复治疗服务的利用。

• DOI: 10.1212/wnl.0000000000005367
• 发表时间: 2018
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Fullard,MichelleE;Willis,AllisonW
• 通讯作者: Willis,AllisonW

Selected autonomic signs and symptoms as risk markers for phenoconversion and functional dependence in prodromal Parkinson's disease.

选择自主神经体征和症状作为帕金森病前驱期表型转变和功能依赖性的风险标记。

• DOI: 10.1007/s10286-022-00889-8
• 发表时间: 2022
• 期刊: Clinical autonomic research : official journal of the Clinical Autonomic Research Society
• 作者: Miller-Patterson,Cameron;Hsu,JesseY;Chahine,LanaM;Morley,JamesF;Willis,AllisonW
• 通讯作者: Willis,AllisonW