Sean Hennessy

Sean Hennessy
University of Pennsylvania | UP · Center for Clinical Epidemiology and Biostatistics

PharmD, PhD

About

343
Publications
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Publications

Publications (343)
Article
Introduction: Statin discontinuation can have major negative health consequences. Studying the reasons for discontinuation can be challenging as traditional data collection methods have limitations. We propose an alternative approach using social media. Methods: We used natural language processing and machine learning to extract mentions of disc...
Article
Full-text available
Purpose: Although dozens of studies have associated vancomycin + piperacillin-tazobactam with increased acute kidney injury (AKI) risk, it is unclear whether the association represents true injury or a pseudotoxicity characterized by isolated effects on creatinine secretion. We tested this hypothesis by contrasting changes in creatinine concentrat...
Article
Background A prior study found that, among advanced non-small cell lung cancer (aNSCLC) patients with PD-L1 expression 50-100% receiving immunotherapy as monotherapy, PD-L1 expression ≥90% was associated with longer survival. We sought to replicate this finding using real-world data from community oncology practices across the US. Methods Retrospe...
Article
Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug‐drug interactions (DDI). We performed high‐throughput screening for clinically relevant DDIs with methadone or buprenorphine by combining pharmacoepidemiologic and pharmacokinetic approaches. We conducted pharmacoepidemiologic screening via a serie...
Article
Background Programmed death or ligand-1 (PD-(L)1) pathway inhibitors, a type of immunotherapy (IO), have become a standard anti-tumor strategy for advanced non-small cell lung cancer (aNSCLC) resulting in improved survival compared to platinum-doublet chemotherapy in PD-L1 expression (PD-L1+e ≥50%) in the 1L treatment setting. Limited evidence to s...
Article
Purpose: Programmed death or ligand-1 (PD-(L)1) pathway inhibitors confer improved survival as first-line treatment for advanced non-small cell lung cancer (aNSCLC) in patients with PD-L1 expression (PD-L1+e ≥50%) compared to platinum-doublet chemotherapy and have become a standard therapy. Some recent evidence suggests that among aNSCLC patients...
Article
Aim: To identify skeletal muscle relaxant (SMR) drug-drug-drug (3DI) signals associated with increased rates of unintentional traumatic injury. Methods: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a se...
Article
Benzodiazepine receptor agonists and related medications, such as Z-drugs and dual orexin receptor antagonists (BZDs), have been associated with unintentional traumatic injury due to their central nervous system (CNS)-depressant effects. Drug-drug interactions (DDIs) may contribute to the known relationship between BZD use and unintentional traumat...
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Full-text available
Growing evidence suggests that drug interactions may be responsible for much of the known association between opioid use and unintentional traumatic injury. While prior research has focused on pairwise drug interactions, the role of higher-order (i.e., drug-drug-drug) interactions (3DIs) has not been examined. We aimed to identify signals of opioid...
Article
Background: Use of muscle relaxants is rapidly increasing in the USA. Little is understood about the role of drug interactions in the known association between muscle relaxants and unintentional traumatic injury, a clinically important endpoint causing substantial morbidity, disability, and death. Objective: We examined potential associations be...
Preprint
There is growing interest in developing causal inference methods for multi-valued treatments with a focus on pairwise average treatment effects. Here we focus on a clinically important, yet less-studied estimand: causal drug-drug interactions (DDIs), quantified by the change of the causal effect of drug $A$ when switching drug $B$ status from "off"...
Article
OBJECTIVE To assess the association of sodium–glucose cotransporter 2 (SGLT2) inhibitors with diabetic ketoacidosis compared with dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a new-user active comparator cohort study to examine two pairwise comparisons: 1) SG...
Article
Aim Fluoroquinolone antibiotics have been implicated in cases of metabolic adverse events. This study investigated the causal association between fluoroquinolones and serious hypoglycemia in those with and without diabetes. Methods We conducted a propensity score-matched cohort study using Optum claims data. We included adults dispensed an oral fl...
Article
Background Fluoroquinolones are associated with central (CNS) and peripheral (PNS) nervous system symptoms, and predicting the risk of these outcomes may have important clinical implications. Both LASSO and random forest are appealing modeling methods, yet it is not clear which method performs better for clinical risk prediction. Purpose To compar...
Article
Full-text available
Objective: We address a first step toward using social media data to supplement current efforts in monitoring population-level medication nonadherence: detecting changes to medication treatment. Medication treatment changes, like changes to dosage or to frequency of intake, that are not overseen by physicians are, by that, nonadherence to medicati...
Article
Objectives Cerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. Statins have increasingly garnered attention as a potential preventive strategy due to their pleiotropic effects beyond lipid-lowering, which may include neuroprotective and anti-epileptogenic properties. We aim to assess the...
Article
Background: Low-dose glucocorticoids are commonly used in the treatment of rheumatoid arthritis (RA). Observational studies have found increased risk of serious infection associated with low-dose glucocorticoids, but concerns about residual confounding remain. Methods: We identified adults with RA on stable immunomodulatory therapy for >6 months...
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Background In a previous drug-drug interaction (DDI) screening study intended to generate hypotheses, clopidogrel + either eszopiclone or zolpidem (vs. clopidogrel alone) were associated with serious bleeding. Objectives To confirm or refute these DDI signals and examine associations with other hypnotics in an independent population of United Stat...
Article
Serious hypoglycemia is a major adverse event associated with insulin secretagogues. Previous studies have suggested a potential relationship between angiotensin‐converting enzyme inhibitors (ACEIs) used with sulfonylureas and serious hypoglycemia, and widely used drug compendia warn of this potential drug‐drug interaction. We investigated the asso...
Article
In vivo studies suggest that arrhythmia risk may be greater with less selective dipeptidyl peptidase‐4 inhibitors, but evidence from population‐based studies is missing. We aimed to compare saxagliptin, sitagliptin, and linagliptin with regard to risk of sudden cardiac arrest (SCA)/ventricular arrhythmia (VA). We conducted high‐dimensional propensi...
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Recent genetic data can offer important insights into the roles of lipoprotein subfractions and particle sizes in preventing coronary artery disease (CAD), as previous observational studies have often reported conflicting results. We used the LD score regression to estimate the genetic correlation of 77 subfraction traits with traditional lipid pro...
Article
Introduction Free drug samples are not captured in the pharmacy claims databases used in many pharmacoepidemiologic studies, which could lead to misclassification of drug exposure status and thus bias study results. Areas Covered We systematically searched the literature in PubMed/MEDLINE, Embase, and Scopus from database inception to August 2020...
Article
Background: Fluoroquinolones, one of the most commonly prescribed antibiotic classes, have been implicated in cases of central nervous system (CNS) and peripheral nervous system (PNS) adverse events, which highlights the need for epidemiologic studies of the neurological safety of fluoroquinolones. Purpose: To evaluate the safety of fluoroquinol...
Article
Antidepressants are very widely used and associated with traumatic injury, yet little is known about their potential for harmful drug interactions. We aimed to identify potential drug interaction signals by assessing concomitant medications (precipitant drugs) taken with individual antidepressants (object drugs) that were associated with unintentio...
Article
BACKGROUND: Diabetes mellitus is a major global public health issue where self-management is critical to reducing disease burden. Social media has been a powerful tool to understand public perceptions. Public perception of the drugs used for the treatment of diabetes may be useful for orienting interventions to increase adherence. OBJECTIVE: The ai...
Preprint
Full-text available
Objective We address a first step towards using social media data to supplement current efforts in monitoring population-level medication non-adherence: detecting changes to medication treatment. Medication treatment changes, like changes to dosage or to frequency of intake, that are not overseen by a physician are, by that, non-adherence to medica...
Article
Treatment considerations for epilepsy patients requiring anticoagulation are changing, and actual prescribing practices have not been characterized. We used the 2010–2018 Optum Clinformatics® Data Mart Database to estimate the annual prevalence and distinguish the patterns of oral anticoagulants (OACs) co-dispensed with antiepileptic drugs (AEDs) a...
Preprint
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Unmeasured confounding is a key threat to reliable causal inference based on observational studies. We propose a new method called instrumental variable for trend that explicitly leverages exogenous randomness in the exposure trend to estimate the average and conditional average treatment effect in the presence of unmeasured confounding. Specifical...
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Background Efforts to minimize harms from opioid drug interactions may be hampered by limited evidence on which drugs, when taken concomitantly with opioids, result in adverse clinical outcomes. Objective To identify signals of opioid drug interactions by identifying concomitant medications (precipitant drugs) taken with individual opioids (object...
Preprint
BACKGROUND Diabetes mellitus is a major global public health issue where self-management is critical to reducing disease burden. Public perception of drugs used to treat the disease may be useful for orienting interventions to increase adherence. OBJECTIVE To explore the perceptions of anti-diabetic drugs (ADDs) through the analysis of health-rela...
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Full-text available
Background Diabetes mellitus is a major global public health issue where self-management is critical to reducing disease burden. Social media has been a powerful tool to understand public perceptions. Public perception of the drugs used for the treatment of diabetes may be useful for orienting interventions to increase adherence. Objective The aim...
Article
Full-text available
Introduction: There are few studies assessing how data on adverse drug events from consumers on social media compare with other sources. Aim: The aim of this study was to assess the consistency of adverse event data of statin medications from social media as compared with other sources. Methods: We collected data on the adverse events of stati...
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Objectives: It is not known how medication adherence changes after hospitalization for a sentinel thromboembolic event. The purpose of this study is to examine the impact of hospitalization for ischemic stroke or thromboembolism on post-discharge adherence to oral anticoagulants in atrial fibrillation patients. Design: We conducted a quasi-experim...
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Background: Adherence to chronic medications remains poor in practice. There is limited evidence on how hospitalization affects post-discharge adherence to oral anticoagulants (OACs) in individuals with atrial fibrillation (AF). The aim of this study is to examine the impact of hospitalization and medication switching on post-discharge adherence t...
Article
Purpose To measure incidence rates of and risk factors for opioid overdose among new users of prescription opioids in the Medicaid population. Methods A cohort study using Medicaid claims from four states (1999‐2012) among adults continuously enrolled in Medicaid for ≥3 years free of opioid prescriptions and opioid overdose before cohort entry. Ex...
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Importance Statins are prescribed to help lower cholesterol levels but have poor adherence rates. Attitudes or beliefs toward medications are important to ascertain because they may be associated with patient behavior. Objective To identify health-related discussion in Twitter posts mentioning a statin and analyze the content within these posts....
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Importance Little is known to date about national trends in the prescribing of skeletal muscle relaxants (SMRs), the use of which is associated with important safety concerns, especially in older adults and in those who use concomitant opioids. Objective To measure national trends in SMR prescribing over a 12-year period. Design, Setting, and Par...
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Sulfonylureas are commonly used to treat type 2 diabetes mellitus. Despite awareness of their effects on cardiac physiology, a knowledge gap exists regarding their effects on cardiovascular events in real-world populations. Prior studies reported sulfonylurea-associated cardiovascular death but not serious arrhythmogenic endpoints like sudden cardi...
Article
Drug interactions between warfarin and sulfonylureas are suggested by pharmacokinetic information and prior studies. However, clinical evidence on the association of such interactions and the risk of bleeding is lacking. Using health care claims data from five US Medicaid programs from 1999‐2011 and a self‐controlled case series design with warfari...
Article
Objective To examine the national prevalence of pharmacological treatment of affective disorders in older adults with Parkinson's disease (PD), and determine the prevalence and risk factors for receipt of an American Geriatrics Society Beers Criteria defined Potentially Inappropriate Medication (PIM) for affective disorder treatment. Design Cross-...
Article
Background: Cyclooxygenase-2 (COX-2) has been found to be important for fracture-healing in animal models, raising concerns about use of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors after fractures. We evaluated associations of NSAIDs, COX-2 inhibitors, and opioids with nonunion after long-bone fracture. Methods:...
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Background Nonsteroidal anti-inflammatory drugs (NSAIDS) are increasingly important alternatives to opioids for analgesia during hospitalization as health systems implement opioid-minimization initiatives. Increasing NSAID use may increase AKI rates, particularly in patients with predisposing risk factors. Inconclusive data in outpatient population...
Article
Background: impairments in neurotransmitter pathways put Parkinson's disease (PD) patients at risk for drug-disease interactions and adverse medication events. Objective: to determine the prevalence and risk factors for potentially inappropriate medication (PIM) prescriptions, as defined by the 2015 Beers List, in PD. Methods: cross-sectional...
Article
Drug‐drug interactions (DDIs) with oral anticoagulants may lead to under‐anticoagulation and increased risk of thromboembolism. While warfarin is susceptible to numerous DDIs, few studies have examined DDIs resulting in thromboembolism or those involving direct‐acting oral anticoagulants (DOACs). We aimed to identify medications that increase the r...
Article
Amiodarone inhibits warfarin metabolism and is associated with major bleeding during warfarin therapy. Managing this drug‐drug interaction (DDI) is challenging because of substantial interpatient variability in DDI magnitude. Because renal dysfunction induces changes in drug metabolism and protein binding that could alter cytochrome P450 inhibition...
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Background: The low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic e...
Article
Background: In 2014, the U.S. Drug Enforcement Agency reclassified hydrocodone from Schedule III to Schedule II of the Controlled Substances Act, resulting in new restrictions on refills. The authors hypothesized that hydrocodone rescheduling led to decreases in total opioid dispensing within 30 days of surgery and reduced new long-term opioid dis...
Article
Introduction: Cerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. As prophylactic use of antiepileptic drugs remains controversial, statins have garnered attention as an alternate preventive strategy due to pleiotropic effects, beyond lipid-lowering, which may include neuroprotective and...
Article
Objective: In 2016, the U.S. Food and Drug Administration (FDA) revised metformin's label to permit use in patients with mild-moderate chronic kidney disease. We sought to determine if this change was associated with increased reports of metformin-associated lactic acidosis (MALA) to the FDA's Adverse Event Reporting System (FAERS). Research desi...
Chapter
Interest in the field of pharmacoepidemiology by the pharmaceutical industry, government agencies, new trainees, and the public has increased greatly, and the realization of what pharmacoepidemiology can contribute to evaluating drug safety and comparative drug effectiveness has similarly increased. These trends will secure the continued increased...
Chapter
A drug–drug interaction (DDI) occurs when one or more drugs affect the pharmacokinetics and/or pharmacodynamics of one or more other drugs. Pharmacoepidemiology studies are the principal way of studying the health effects of potential DDIs. A number of methodologic problems are more prominent in pharmacoepidemiologic studies of DDIs than in those e...
Article
Objective: To determine the association between preoperative benzodiazepine and nonbenzodiazepine receptor agonist ("Z-drugs") use and adverse outcomes after surgery. Background: Prescriptions for benzodiazepines and Z-drugs have increased over the past decade. Despite this, the association of preoperative benzodiazepines and Z-drug receipt with...
Article
Full-text available
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Article
Purpose: The ability of the Clinical Practice Research Datalink (CPRD) to ascertain all-cause hospitalizations remains unknown. We determined the proportion of hospitalizations in CPRD that were also recorded in Hospital Episode Statistics (HES), and vice versa, among patients initiating oral antidiabetic (OAD) therapy. Methods: We conducted a r...
Preprint
Full-text available
Lipoprotein subfractions and particle sizes are increasingly used in observational studies to predict the risk of cardiovascular diseases. However, the causal role of the different subfractions remain largely uncertain because the conventional study designs are subject to unmeasured confounding. We used Mendelian randomization and public GWAS summa...
Preprint
In October 2014, the US Drug Enforcement Agency (DEA) reclassified hydrocodone from Schedule III to Schedule II of the Controlled Substances Act, resulting in a prohibition on refills in the initial prescription. While this schedule change was associated with overall decreases in the rate of filled hydrocodone prescriptions and opioid dispensing, a...
Article
Few population‐based studies have examined bleeding associated with clopidogrel drug‐drug interactions (DDIs). We sought to identify precipitant drugs taken concomitantly with clopidogrel (an object drug) that increased serious bleeding rates. We screened 2000–2015 Optum commercial health insurance claims to identify DDI signals. We performed self‐...
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Full-text available
High temperature increases all-cause mortality. Thermoregulatory ability is impaired in persons with elevated serum cholesterol, but can be improved by the administration of statins, even in the short-term. We investigated whether the impact of high temperature (≥24 °C) on all-cause mortality among socioeconomically disadvantaged adults with a curr...
Article
Purpose One response to the opioid crisis in the United States has been the development of opioid analgesics with properties intended to reduce non‐oral use. Previous evaluations of abuse in the community have relied on population averaged interrupted time series Poisson models with utilization offsets. However, competing interventions and secular...
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Full-text available
Objective Heat is associated with elevated all-cause mortality, and furosemide-induced potassium depletion might be worsened by heat-induced sweating. Because empiric potassium is associated with a marked survival benefit in users of furosemide at a dose of ≥40 mg/day, we hypothesised that this empiric potassium’s survival benefit would increase wi...
Article
Background The US Food and Drug Administration’s Sentinel System was established to monitor safety of regulated medical products. Sentinel investigators identified known associations between drugs and adverse events to test reusable analytic tools developed for Sentinel. This test case used a comparator with a different indication. Objective We te...