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    Crowdsourcing Analysis of Off-label Intervention Usage in Amyotrophic Lateral Sclerosis

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    Date
    2017-05
    Author
    Mertens, Benjamin Isaac
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    Abstract
    Background Amyotrophic Lateral Sclerosis is a neurodegenerative disease resulting in death within 3-5 years. Only riluzole is widely prescribed by clinicians to target the ALS etiology. Most interventions prescribed are “off-label”, meaning they were not developed for ALS, but are used to treat ALS or co-morbid symptoms. We examine relationships between intervention usage, disease duration, and sub-population characteristics (onset age, onset type, gender). Methods A form of physician crowdsourcing was utilized to examine intervention usage in a retrospective cohort of 1,585 ALS patients. Data was compiled on a per-visit and per-patient basis. Interventions were aggregated by active ingredient or indication. Principal component analysis (PCA), Fisher exact test, Kaplan Meir, and conditional random forest were used to determine the significance of relationships between patient characteristics, intervention usage, and disease duration. Results A total of 4,168 individual interventions and 564 intervention categories were identified in the cohort. A total 54 intervention categories met the threshold for statistical assessment (e.g. >8.5% usage prevalence); 19 corresponded to statistically significant (p<0.05) increases in disease duration ranging from +4.5-6.5 months. Interventions identified by random forest as the strongest predictors of disease duration (all p<0.01), are: vitamin A (+8.9 months), multivitamin (+8.2 months), feeding tube (+15.5 months), alternative herbal supplements (+9.7 months), antihistamines (+8.4 months), muscle relaxants (+13.4 months), stimulant laxatives (+7.1 months), anti-spasticity (+16.4 months). Usage of anti-cholinergic, anti-depressant, and non-opioid pain medication also resulted in a statistically significant (p<0.05) increase in survival duration (+6.2, +16.4 months, and +15.2 months, respectively). Riluzole, used by 60% of the cohort, increased disease duration by 1.3 months, albeit insignificantly (p>0.05). No interventions resulted in a significant decrease in survival duration. Female patients used more interventions than males, but gender was not an independent predictor of survival. Conclusions We found many “off-label” interventions perform better than the ALS-specific drug, riluzole. Our findings illustrate the complexity of variables contributing to ALS disease duration. Multiple interventions that increase overall health and quality of life, irrespective of whether they specifically target ALS etiology, profoundly increase survival duration likely by boosting “will to live”.
    URI
    http://hdl.handle.net/1853/61350
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    • Department of Biomedical Engineering Undergraduate Research Option Theses [214]
    • Undergraduate Research Option Theses [862]

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