ADS Capstone Chronicles Revised

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‭individual‬ ‭differences,‬ ‭especially‬ ‭weight,‬ ‭sex,‬ ‭and‬ ‭age‬ ‭in‬ ‭people‬ ‭taking‬ ‭certain‬ ‭medications‬‭are‬‭related‬‭to‬ ‭death‬ ‭and‬ ‭serious‬ ‭outcomes.‬ ‭For‬ ‭males,‬ ‭age‬ ‭increases‬ ‭with‬ ‭seriousness‬ ‭and‬ ‭weight‬ ‭decreases‬ ‭with‬ ‭seriousness,‬ ‭showing‬ ‭that‬ ‭in‬ ‭general,‬ ‭older‬ ‭age‬ ‭and‬ ‭lower‬ ‭weights‬ ‭are‬ ‭associated‬ ‭with‬ ‭more‬ ‭serious‬ ‭outcomes.‬ ‭However,‬ ‭females‬ ‭show‬ ‭a‬ ‭different‬ ‭pattern.‬ ‭Age‬ ‭increases‬‭and‬ ‭weight‬ ‭decreases‬ ‭from‬ ‭nonserious‬ ‭to‬ ‭serious‬ ‭,‬ ‭but‬ ‭for‬ ‭death‬ ‭,‬ ‭younger,‬ ‭overweight‬ ‭females‬ ‭are‬ ‭at‬ ‭risk‬ ‭(Figure‬ ‭8a,b).‬ ‭Females‬ ‭with‬ ‭death‬ ‭outcome‬ ‭have‬ ‭similar‬ ‭younger‬ ‭ages‬ ‭to‬ ‭males‬ ‭experiencing‬ ‭nonserious‬ ‭events‬ ‭(‬ ‭p‬ ‭=‬ ‭.12),‬ ‭males‬‭with‬ ‭death‬ ‭outcome‬ ‭have‬ ‭similar‬ ‭lower‬ ‭weights‬ ‭to‬ ‭females‬ ‭with‬ ‭nonserious‬ ‭outcome‬ ‭(‬ ‭p‬ ‭=‬ ‭.79),‬ ‭and‬ ‭males‬ ‭with‬ ‭nonserious‬ ‭outcome‬ ‭have‬ ‭similar‬ ‭higher‬ ‭weight‬ ‭to‬ ‭females‬ ‭with‬ ‭death‬ ‭outcome (‬ ‭p‬ ‭= .38).‬ ‭As‬‭for‬‭the‬‭predictor‬‭drug‬‭features,‬‭the‬‭higher‬ ‭splits‬‭in‬‭the‬‭random‬‭forest‬‭model‬‭were‬‭drugs‬ ‭related‬ ‭to‬ ‭nonserious‬ ‭outcomes,‬ ‭which‬ ‭makes‬ ‭sense‬ ‭since‬ ‭72%‬ ‭of‬ ‭nonserious‬ ‭outcomes‬ ‭are‬ ‭related‬ ‭to‬‭a‬‭single‬‭drug‬‭called‬ ‭Dupixent‬ ‭which‬ ‭treats‬ ‭a‬ ‭variety‬ ‭of‬ ‭inflammatory‬ ‭conditions‬ ‭in‬ ‭the‬ ‭sinuses,‬ ‭lungs,‬‭and‬‭skin.‬ ‭Serious‬ ‭and‬ ‭death‬ ‭outcomes‬ ‭are‬ ‭related‬ ‭to‬ ‭a‬ ‭wider‬ ‭range‬ ‭of‬ ‭drugs,‬ ‭with‬ ‭the‬ ‭top‬ ‭reported‬ ‭representing‬ ‭only‬‭27%‬‭and‬ ‭24%‬ ‭of‬ ‭the‬ ‭sample,‬ ‭respectively.‬ ‭Thus,‬ ‭the‬ ‭child‬‭node‬‭patterns‬‭in‬‭the‬‭trees‬‭become‬‭more‬ ‭complex‬‭with‬‭the‬‭variety‬‭of‬‭drugs‬‭related‬‭to‬ ‭serious‬ ‭and‬ ‭death‬ ‭outcomes.‬ ‭For‬ ‭serious‬ ‭outcome,‬ ‭most‬ ‭drugs‬ ‭are‬ ‭forms‬ ‭of‬ ‭chemotherapy.‬ ‭For‬ ‭death‬ ‭outcome,‬ ‭the‬ ‭drugs‬‭are‬‭indicated‬‭for‬‭inflammation,‬‭cancer‬ ‭treatment, and pain relief.‬ ‭The‬ ‭risk‬ ‭factors‬ ‭in‬ ‭the‬ ‭model‬ ‭suggest‬ ‭that‬ ‭differences‬ ‭in‬ ‭pharmacokinetics‬ ‭are‬ ‭related‬ ‭to‬ ‭adverse‬ ‭outcomes.‬ ‭Pharmacokinetics‬ ‭is‬ ‭the‬ ‭movement‬ ‭and‬ ‭metabolism‬ ‭of‬ ‭drug‬ ‭compounds‬ ‭in‬ ‭a‬ ‭living‬ ‭organism.‬ ‭Obesity‬ ‭affects‬ ‭the‬ ‭pharmacokinetics‬ ‭of‬ ‭drug‬ ‭compounds‬‭by‬‭slowing‬‭drug‬‭absorption‬‭rates‬

‭and‬ ‭metabolism‬ ‭based‬ ‭on‬ ‭higher‬ ‭fat‬ ‭mass,‬ ‭and‬ ‭lower‬ ‭water‬ ‭and‬ ‭lean‬ ‭body‬ ‭mass,‬ ‭thus,‬ ‭on‬ ‭average,‬ ‭obese‬ ‭patients‬ ‭should‬ ‭be‬ ‭given‬ ‭smaller‬ ‭doses‬ ‭of‬ ‭drugs‬‭compared‬‭to‬‭healthy‬ ‭individuals‬ ‭with‬ ‭more‬ ‭lean‬ ‭body‬ ‭mass‬ ‭(Gouju‬ ‭&‬ ‭Legeay,‬ ‭2023).‬ ‭This‬ ‭puts‬ ‭obese‬ ‭individuals‬ ‭at‬ ‭risk‬ ‭of‬ ‭overdose‬ ‭and‬ ‭ADRs.‬ ‭Females‬ ‭are‬ ‭at‬ ‭greater‬ ‭risk‬ ‭of‬ ‭death‬ ‭related‬ ‭to‬ ‭opioid,‬ ‭antipsychotic,‬ ‭benzodiazepine,‬ ‭and‬‭antidepressant‬‭medications‬‭compared‬‭to‬ ‭males,‬ ‭possibly‬ ‭due‬ ‭to‬ ‭drug‬ ‭interactions‬ ‭from‬‭lack‬‭of‬‭communication‬‭between‬‭female‬ ‭healthcare‬ ‭providers,‬ ‭or‬ ‭easier‬ ‭access‬ ‭to‬ ‭mental-health‬ ‭drugs‬ ‭compared‬ ‭to‬ ‭males‬ ‭(Iwanicki‬ ‭et‬ ‭al,‬ ‭2015;‬ ‭Wightman‬ ‭et‬ ‭al.,‬ ‭2021).‬ ‭Additionally,‬ ‭there‬ ‭may‬ ‭be‬ ‭a‬ ‭gender‬ ‭gap‬ ‭in‬ ‭clinical‬ ‭trial‬ ‭research‬ ‭for‬ ‭certain‬ ‭compounds‬ ‭whereby‬ ‭recommended‬‭dosages‬ ‭are‬ ‭based‬ ‭on‬ ‭primarily‬ ‭male‬ ‭data.‬ ‭Age‬ ‭affects‬ ‭pharmacokinetics‬ ‭because‬ ‭older‬ ‭individuals‬ ‭are‬ ‭exposed‬ ‭to‬ ‭more‬ ‭drugs‬ ‭overall,‬‭and‬‭certain‬‭epigenetic‬‭signaling‬‭and‬ ‭enzyme‬ ‭production‬ ‭affects‬ ‭the‬ ‭ability‬ ‭to‬ ‭metabolize‬ ‭drug‬ ‭compounds‬ ‭as‬ ‭people‬ ‭age‬ ‭(Duecker & Brockmoeller, 2019).‬ ‭The‬ ‭patterns‬ ‭between‬ ‭these‬ ‭risk‬ ‭factors‬ ‭can‬ ‭be‬ ‭nonlinear,‬ ‭which‬ ‭is‬ ‭reflected‬ ‭in‬ ‭the‬ ‭high‬ ‭performance‬ ‭of‬ ‭the‬ ‭decision‬ ‭tree‬ ‭based‬ ‭models‬ ‭and‬ ‭lower‬ ‭performance‬‭in‬‭the‬‭linear‬ ‭models,‬ ‭and‬ ‭the‬‭lack‬‭of‬‭correlation‬‭between‬ ‭numerical features (Figure 9).‬ ‭6.2 Limitations‬ ‭This‬ ‭project‬ ‭has‬ ‭limitations‬ ‭resulting‬ ‭from‬ ‭the‬‭nature‬‭of‬‭FAERS‬‭data‬‭and‬‭the‬‭FDA‬‭data‬ ‭infrastructure,‬ ‭but‬ ‭which‬ ‭can‬ ‭be‬ ‭addressed‬ ‭with future analyses.‬ ‭The‬ ‭interpretation‬ ‭of‬ ‭the‬ ‭results‬ ‭cannot‬ ‭be‬ ‭extrapolated‬ ‭to‬ ‭the‬ ‭entire‬ ‭population‬ ‭of‬ ‭people‬ ‭using‬ ‭the‬ ‭drugs‬ ‭reported‬ ‭in‬ ‭FAERS.‬ ‭The‬ ‭conclusions‬ ‭and‬ ‭insights‬ ‭can‬ ‭only‬ ‭be‬ ‭applied‬ ‭to‬ ‭people‬ ‭who‬ ‭take‬ ‭the‬ ‭drugs‬ ‭reported‬ ‭in‬ ‭FAERS‬ ‭and‬ ‭who‬ ‭also‬ ‭had‬ ‭healthcare‬ ‭providers‬‭make‬‭a‬‭report‬‭for‬‭them‬ ‭in‬ ‭FAERS.‬ ‭Thus,‬ ‭the‬ ‭results‬ ‭only‬ ‭apply‬ ‭to‬

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