Pharmacotherapies in Parkinson Disease: Investigating Trends and Adverse Health Outcomes
Bibliographic record
Abstract
Parkinson disease (PD) is the second most common neurodegenerative disease worldwide, with estimates suggesting that PD prevalence and incidence will increase with aging populations. Therapeutic options and clinical guidelines for PD have significantly changed over the past 15 years; however, pharmacoepidemiology data in PD are lacking, especially regarding adverse effects of non-ergot dopamine agonists (DAs) and outcomes associated with anticholinergic burden. The objectives of this doctoral research are threefold: 1) examine patterns of antiparkinson drug use in relation to clinical guideline publication, drug availability, and emerging safety concerns; 2) determine whether PD patients treated with non-ergot DAs are at increased risk of adverse cardiovascular or cerebrovascular outcomes; and 3) determine whether anticholinergic burden is associated with adverse outcomes in PD. Specific research questions were investigated using epidemiological methods and electronic health data from Cerner Health Facts®, an electronic medical record database that stores time-stamped patient records for more than 300 Cerner subscribing facilities across the United States. Findings from this work are reported in a series of manuscripts, all of which have been published. Key findings include: 1) DA use began declining in 2007, from 34% to 27% in 2012. The decline followed publication of the American Academy of Neurology’s practice parameter refuting levodopa toxicity, pergolide withdrawal, and pramipexole label revisions; 2) heart failure was the only adverse cardiovascular or cerebrovascular outcome that demonstrated a significant association with non-ergot DA use, mainly pramipexole; and 3) anticholinergic burden in PD was associated with the diagnosis of fracture and delirium, and significantly increased the risk of emergency department visit and readmission post inpatient discharge. Reported antiparkinson prescribing trends suggest that safety and best practice information may be communicated effectively in PD. Although findings warrant replication, individuals with PD and independent risk factors for or a history of heart failure may benefit from limited use of pramipexole. Similarly, individuals with PD may benefit from substituting non-PD medications with anticholinergic effects for equally effective non-anticholinergic agents. Additional pharmacovigilance studies are needed to better understand health risks and the impact of population health interventions in PD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.015 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.005 | 0.011 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".