Warren Bilker

Warren Bilker
University of Pennsylvania | UP · Department of Biostatistics , Epidemiology, and Informatics

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490
Publications
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Introduction

Publications

Publications (490)
Article
Background Reported β-lactam allergies (BLA) are common and frequently inaccurate, but there are limited data on the clinical implications of BLA among solid organ transplant (SOT) recipients. We examined the impact of BLA on clinical outcomes and antibiotic use among SOT recipients. Methods This retrospective cohort study included adult patients...
Article
Background: The clinical outcomes associated with, and risk factors for, carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) in solid organ transplant (SOT) recipients remain ill-defined. Methods: A multicenter retrospective cohort study was performed, including SOT recipients with an Enterobacterales BSI between 2005 and 2...
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
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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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
It has been suggested that pets play a critical role in the maintenance of methicillin‐resistant (MR) and multidrug‐resistant (MDR) Staphylococcus spp. in the household. We examined risk factors for carriage of antimicrobial‐resistant coagulase‐positive staphylococci, with particular attention to Staphylococcus aureus and Staphylococcus pseudinterm...
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...
Article
Background: Multidrug-resistant organisms (MDROs) frequently contaminate hospital environments. We performed a multicenter, cluster-randomized, crossover trial of two methods for monitoring of terminal cleaning effectiveness. Methods: Six intensive care units (ICUs) at three medical centers received both interventions sequentially, in randomized...
Article
Background The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of post-transplant infection, graft failure, and mortality. Methods A multicenter retrospective cohort study was per...
Article
Background: People with HIV (PWH) smoke tobacco at much higher rates than the general population. Prior research has shown that PWH have faster nicotine metabolism than HIV-uninfected individuals which may underlie this disparity, but the cause is unknown. We investigated whether higher nicotine metabolite ratio (NMR; 3-hydroxycotinine:cotinine),...
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Background Multidrug-resistant (MDR) Gram-negative (GN) bloodstream infections (BSI) are a major cause of morbidity and mortality among solid organ transplant recipients (SOTR). We determined risk factors associated with subsequent MDR-GN BSI following an initial Enterobacterales (EB) BSI among SOTRs. Methods A retrospective cohort study was perfo...
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Background With the ongoing opioid epidemic in the US, there has been an increase in the proportion of deceased organ donors with a history of injection drug use (IDU), raising concern for additional infectious risks to transplantation.We sought to determine how recent IDU among deceased organ donors impacted donor culture results. Methods A retro...
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Motivational deficits play a central role in disability due to negative symptoms of schizophrenia (SZ), but limited pathophysiological understanding impedes critically needed therapeutic development. We applied an fMRI Effort Discounting Task (EDT) that quantifies motivation using a neuroeconomic decision-making approach, capturing the degree to wh...
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Opioids relieve acute pain, but there is little evidence to support the stability of the benefit over long-term treatment of chronic noncancer pain. Previous systematic reviews consider only group level published data which did not provide adequate detail. Our goal was to use patient-level data to explore the stability of pain, opioid dose, and eit...
Article
Background Inappropriate antibiotic prescribing is common in primary care (PC), particularly for respiratory tract diagnoses (RTDs). However, the optimal approach for improving prescribing remains unknown. Methods We conducted a stepped-wedge study in PC practices within a health system to assess the impact of a provider-targeted intervention on a...
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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...
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Objective Cancer drug stockouts occur at high frequencies globally, however, their effects on treatment are understudied in sub-Saharan Africa (SSA). We aimed to determine whether causes of suboptimal cancer treatment prescriptions differed between periods of stockout and full treatment supply. Design A retrospective cohort study of systemic thera...
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...
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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...
Article
Antibiotic use in deceased organ donors has not been previously described. In a retrospective cohort of 440 donors, we found 427 (97%) received at least one antibiotic course, 312 (71%) received broad-spectrum antibiotics, and 61 (14%) received potentially redundant antibiotics during their terminal hospitalization, suggesting a need for stewardshi...
Article
Background Multidrug‐resistant Gram‐negative bacterial infections are increasingly common among solid organ transplant (SOT) recipients, leading to challenges in the selection of empiric antimicrobial therapy. We sought to develop a clinical tool to predict which SOT recipients are at high risk for extended‐spectrum beta‐lactamase (ESBL)‐producing...
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...
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The parieto-frontal integration theory (PFIT) identified a fronto-parietal network of regions where individual differences in brain parameters most strongly relate to cognitive performance. PFIT was supported and extended in adult samples, but not in youths or within single-scanner well-powered multimodal studies. We performed multimodal neuroimagi...
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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...
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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Background: Tobacco use is prevalent amongst individuals infected with human immunodeficiency virus (HIV). In resource-constrained settings, pharmacological smoking cessation interventions are unfeasible because of their high cost. There is a need to develop and evaluate behavioural interventions to address the unique challenges of tobacco use in t...
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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...
Article
Objective Evaluate the clinical impact of the implementation of VERIGENE gram-positive blood culture testing (BC-GP) coupled with antimicrobial stewardship result notification for children with positive blood cultures. Design Quasi-experimental study. Setting Quaternary children’s hospital. Patients Hospitalized children aged 0–21 years with pos...
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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...
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Multiple lines of evidence point to glutamatergic signaling in the postsynaptic density (PSD) as a pathophysiologic mechanism in schizophrenia. Integral to PSD glutamatergic signaling is reciprocal interplay between GluN and mGluR5 signaling. We examined agonist-induced mGluR5 signaling in the postmortem dorsolateral prefrontal cortex (DLPFC) deriv...
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
Background: Approximately 40% of all Enterobacterales (EB) bloodstream infections (BSI) among solid organ transplant recipients (SOTR) are due to extended-spectrum beta-lactamase (ESBL)-producing organisms, but risk factors for such infections remain ill-defined in this population. Thus, we sought to determine the risk factors for ESBL-EB BSI amon...
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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
The extent to which donor multidrug‐resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at four transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed d...
Article
Social affiliative behavior is an important component of everyday life in many species and is likely to be disrupted in disabling ways in various neurodevelopmental and neuropsychiatric disorders. Therefore, determining the mechanisms involved in these processes is crucial. A link between N‐methyl‐D‐aspartate (NMDA) receptor function and social beh...
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Background Transplant guidelines recommend exercising caution when considering organs that may be infected or colonized with multidrug-resistant organisms (MDROs) and treating the organ recipient with perioperative antibiotics active against the donor MDRO. Unfortunately, donor MDROs are often identified only after transplantation. We developed a c...
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Background Antimicrobial stewardship often focuses on inpatients, yet inappropriate antimicrobial use is common in the outpatient setting. We performed a prospective, stepped wedge interventional study to assess the impact of an educational and feedback-based intervention on prescribing practices for respiratory tract infections (RTIs) in the adult...
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
We implemented a guideline for appropriate acid suppressant use in hematology-oncology patients. This intervention resulted in a sustained reduction in proton pump inhibitor (PPI) use without an increase in rates of gastrointestinal bleeding. Practice guidelines are effective in reducing PPI use, which is associated with risk of Clostridioides diff...
Article
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical is...
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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
Donor infection or colonization with a multidrug‐resistant organism (MDRO) impacts organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four tr...
Preprint
Full-text available
Cognitive ability is a complex product of brain processes, yet it remains unknown how brain structure and function together lead to individual differences in developing cognitive skills. We performed multimodal neuroimaging in 1601 youths age 8-22 on the same 3-Tesla Magnetic Resonance Imaging scanner with contemporaneous neurocognitive assessment....
Article
Social impairment occurs across the psychosis spectrum, but its pathophysiology remains poorly understood. Here we tested the hypothesis that reduced differential responses (aversive vs. neutral) in neural circuitry underpinning aversive conditioning of social stimuli characterizes the psychosis spectrum. Participants age 10–30 included a healthy c...
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‐...
Article
e18129 Background: Cancer drug stockouts occur at high frequencies globally, however their clinical effects are understudied in sub-Saharan Africa (SSA). We aim to describe prescription patterns and cost of systemic chemotherapy in cancer patients in Botswana during periods of stockout. Methods: Using a retrospective cohort study of the ten most co...
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PURPOSE Essential cancer medicine stock outs are occurring at an increasing frequency worldwide and represent a potential barrier to delivery of standard therapy in patients with cancer in low- and middle-income countries. The objective of this study was to measure the impact of cancer medicine stock outs on delivery of optimal therapy in Botswana....
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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...
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Background Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to increase. We sought to create a clinical prediction tool for community-onset UTIs due to extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (formerly Enterobacteriaceae, EB). Methods A case-control st...
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Background Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to emerge. We sought to determine the association between extended-spectrum cephalosporin resistance (ESC-R) and recurrence among Enterobacteriaceae (EB) UTIs. Methods A retrospective cohort study was performed. All pat...
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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
Data regarding cancer risk for individuals who were exposed to traumatic and stressful life events are conflicting. We sought to evaluate the association between posttraumatic stress disorder (PTSD) and the risk of the four most common solid tumors: lung, breast, prostate, and colorectal cancers. We conducted four nested case‐control studies using...
Article
Blood culture utilization at an academic hospital: Addressing a gap in benchmarking – CORRIGENDUM - Volume 39 Issue 12
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Background Healthcare-associated infections (HAIs) and multidrug-resistant organisms (MDROs) remain critically important problems. Although copper has well-described antimicrobial properties, the impact of copper-impregnated linens on HAIs and MDROs in healthcare settings remains undefined. Methods This study was conducted in a 24-bed medical ICU...
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Background Recent data have shown an increase in bacterial resistance to first-line antibiotics used to treat community-onset urinary tract infections (UTIs). A better understanding of the clinical outcomes associated with drug-resistant UTIs in the community is needed. We sought to determine the association between community-onset extended-spectru...
Article
Full-text available
Background Multidrug-resistant Gram-negative bacterial infections have emerged as a significant cause of morbidity among solid-organ transplant (SOT) recipients, leading to challenges in selection of empiric antibiotic therapy. As such, we developed a predictive tool to determine whether these patients are high or low risk for extended-spectrum β-l...
Article
Full-text available
Background Delay in effective antibiotic administration in severe infections such as bacteremia is associated with worse clinical outcomes. We implemented previously validated software that uses real-time predictive modeling to determine patient-specific antibiograms (PS-ABG). The software allowed prescribers to run the model on their individual pa...
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Background: Biomarkers can facilitate safe antibiotic discontinuation in critically ill patients without bacterial infection. Methods: We tested the ability of a biomarker-based algorithm to reduce excess antibiotic administration in patients with systemic inflammatory response syndrome (SIRS) without bacterial infections (uninfected) in our ped...
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Patients undergoing stem cell transplant (SCT) for the treatment of hematologic malignancy are at increased risk for central line–associated bloodstream infections (CLABSIs). The use of prophylactic antibiotics to prevent CLABSIs in the setting of autologous SCT is of unclear benefit. We aimed to evaluate the impact of levofloxacin prophylaxis on r...
Article
Objective Resistance to extended-spectrum cephalosporins (ESC) among Enterobacteriaceae (EB) is increasingly prevalent. We sought to determine the clinical outcomes associated with community-onset ESC-resistant (ESC-R) EB urinary tract infections (UTIs) in a US health system. Design Retrospective cohort study. Patients All patients presenting to...
Article
Background: Cancer drug shortages represent a complex global issue with potentially adverse survival outcomes. Up to 98% of oncologists and pharmacists surveyed in North America reported at least 1 drug shortage in the prior year and 66% reported at least one patient who had clinical care impacted by the shortage. In low- and middle-income countrie...
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Objective To describe the pattern of blood culture utilization in an academic university hospital setting. Design Retrospective cohort study. Setting A 789-bed tertiary-care university hospital that processes 40,000+blood cultures annually. Methods We analyzed blood cultures collected from adult inpatients at the Hospital of the University of Pe...
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In this multicenter study, we identified an increased risk of 30-day mortality among hospitalized children with carbapenem-resistant Enterobacteriaceae (CRE) isolated from clinical cultures compared to those with carbapenem-susceptible Enterobacteriaceae (CSE). We additionally report significant variation in antibiotic treatment for children with C...