Publications

2017

Fitzpatrick, Margaret A, Katie J Suda, Charlesnika T Evans, Robert J Hunkler, Frances Weaver, and Glen T Schumock. (2017) 2017. “Influence of Drug Class and Healthcare Setting on Systemic Antifungal Expenditures in the United States, 2005-15.”. American Journal of Health-System Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists 74 (14): 1076-83. https://doi.org/10.2146/ajhp160943.

PURPOSE: Overall and specific class trends in systemic antifungal expenditures in various U.S. healthcare settings from 2005 through 2015 were evaluated.

METHODS: Systemic antifungal expenditures from January 1, 2005, through December 31, 2015, were obtained from the QuintilesIMS National Sales Perspective database, which provides a statistically valid projection of medication purchases from multiple markets throughout the United States. Summary data for total antifungal expenditures over the entire period are reported, as are growth and the percentage change in expenditures from one year to the next. Expenditures were also assessed specifically by year, class, and healthcare setting. Expenditure trends over the study period were assessed using simple linear trend regression models.

RESULTS: Overall expenditures for the 11-year period were $9.37 billion. The greatest proportion of expenditures occurred in nonfederal hospitals (47.2%) and for triazoles (57.6%). From 2005 through 2015, total expenditures decreased from $1.1 billion to $894 million (-18.8%, p = 0.09); however, expenditures in clinics and retail pharmacies increased (202%, p < 0.01, and 13.8%, p = 0.04, respectively), a trend most pronounced after 2012. Expenditures for flucytosine also increased (968.1%, p < 0.01), particularly in clinics where there was a dramatic 6,640.9% increase (p < 0.01).

CONCLUSION: From 2005 through 2015, an increase in systemic antifungal expenditures was observed in community settings, despite an overall decrease in total antifungal expenditures in the United States. Large increases in flucytosine expenditures were observed, particularly in the community.

Evans, Charlesnika T, Margaret A Fitzpatrick, Makoto M Jones, Stephen P Burns, Linda Poggensee, Swetha Ramanathan, Sherri L LaVela, Nasia Safdar, and Katie J Suda. (2017) 2017. “Prevalence and Factors Associated With Multidrug-Resistant Gram-Negative Organisms in Patients With Spinal Cord Injury.”. Infection Control and Hospital Epidemiology 38 (12): 1464-71. https://doi.org/10.1017/ice.2017.238.

OBJECTIVE Infections caused by multidrug-resistant gram-negative organisms (MDRGNOs) have been increasing every year. The objective of this study was to describe the prevalence of MDRGNOs and factors associated with MDRGNOs in patients with spinal cord injury or disorder (SCI/D). DESIGN Retrospective cohort study. METHODS Department of Veterans Affairs (VA) electronic health record data from 142 VA facilities were evaluated for 19,642 patients with SCI/D. Multivariable cluster-adjusted models were fit to identify factors associated with MDRGNO. RESULTS Gram-negative (GN) cultures occurred in 44% of patients with SCI/D receiving care at VA facilities, and 11,527 (41.3%) GN cultures had an MDRGNO. The most frequent GN organisms (GNOs) were Escherichia coli (28.5%), Klebsiella pneumoniae (17.0%), and Pseudomonas aeruginosa (16.0%). Two-thirds of GN cultures were from the outpatient setting, where MDRGNO prevalence was 37.6%. Significant geographic variation in the prevalence of MDRGNOs was identified (South, 44.7%; Northeast, 44.3%; West, 36.8%; Midwest, 34.4%). Other factors associated with an MDRGNO were older age, injury characteristics, comorbidities, specimen type, healthcare setting, and healthcare exposure. Black (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.39-1.78) and Hispanic race (OR, 1.58; 95% CI, 1.28-1.95), polymicrobial culture (OR, 2.67; 95% CI, 2.46-2.90), and antibiotic use in the previous 90 days (OR, 1.62; 95% CI, 1.50-1.76) were also associated with having an MDRGNO. CONCLUSIONS MDRGNOs were common in community and healthcare settings among veterans with SCI/D, with significant geographic variation. Health care and antibiotic exposures were significant factors associated with MDRGNOs. Priority should be given to controlling the spread of MDRGNOs in this special population, including a focus on judicious use of antibiotics. Infect Control Hosp Epidemiol 2017;38:1464-1471.

Ramanathan, Swetha, Katie J Suda, Margaret A Fitzpatrick, Linda Poggensee, Sherri L LaVela, Stephen P Burns, and Charlesnika T Evans. (2017) 2017. “Multidrug-Resistant Acinetobacter: Risk Factors and Outcomes in Veterans With Spinal Cord Injuries and Disorders.”. American Journal of Infection Control 45 (11): 1183-89. https://doi.org/10.1016/j.ajic.2017.06.016.

BACKGROUND: Multidrug-resistant (MDR) Acinetobacter is a growing concern and has been identified as a serious threat by the Centers for Disease Control and Prevention. However, there is little information on MDR Acinetobacter in individuals with spinal cord injuries and disorders (SCI/Ds). Therefore, the objective of this study was to identify risk factors for, and assess outcomes of, MDR Acinetobacter in veterans with SCI/Ds.

METHODS: This was a retrospective cohort study from January 1, 2012-December 31, 2013, using national Veterans Affairs medical encounter and microbiology data.

RESULTS: A total of 773 Acinetobacter cultures were identified in 571 patients, of which 58.9% were MDR. Inpatient culture, sputum and other specimen type, receipt of antibiotics within 90 days before culture date, and pressure ulcers were identified as independent predictors of MDR Acinetobacter. Highest odds of MDR Acinetobacter were seen with previous antibiotic use (odds ratio, 7.27; 95% confidence interval, 2.59-20.54). Thirty-day mortality was 5.3% in this study. Multidrug resistance, previous mechanical ventilation 90 days before the culture, and cancer were all independent risk factors for 30-day mortality.

CONCLUSIONS: There should be increased efforts to highlight the importance of antimicrobial stewardship to improve infection control to help limit spread of Acinetobacter in health care settings.

Frazier, Winfred, Gerald Cochran, Wei-Hsuan Lo-Ciganic, Walid F Gellad, Adam J Gordon, Chung-Chou H Chang, and Julie M Donohue. (2017) 2017. “Medication-Assisted Treatment and Opioid Use Before and After Overdose in Pennsylvania Medicaid.”. JAMA 318 (8): 750-52. https://doi.org/10.1001/jama.2017.7818.

This study uses Medicaid data to compare prescription opioid use, duration of opioid use, and rates of medication-assisted treatment (buprenorphine, methadone, or naltrexone) among enrollees before and after an overdose event.

Rottman, Benjamin Margolin, Zachary A Marcum, Carolyn T Thorpe, and Walid F Gellad. (2017) 2017. “Medication Adherence As a Learning Process: Insights from Cognitive Psychology.”. Health Psychology Review 11 (1): 17-32. https://doi.org/10.1080/17437199.2016.1240624.

Non-adherence to medications is one of the largest contributors to sub-optimal health outcomes. Many theories of adherence include a 'value-expectancy' component in which a patient decides to take a medication partly based on expectations about whether it is effective, necessary, and tolerable. We propose reconceptualising this common theme as a kind of 'causal learning' - the patient learns whether a medication is effective, necessary, and tolerable, from experience with the medication. We apply cognitive psychology theories of how people learn cause-effect relations to elaborate this causal-learning challenge. First, expectations and impressions about a medication and beliefs about how a medication works, such as delay of onset, can shape a patient's perceived experience with the medication. Second, beliefs about medications propagate both 'top-down' and 'bottom-up', from experiences with specific medications to general beliefs about medications and vice versa. Third, non-adherence can interfere with learning about a medication, because beliefs, adherence, and experience with a medication are connected in a cyclic learning problem. We propose that by conceptualising non-adherence as a causal-learning process, clinicians can more effectively address a patient's misconceptions and biases, helping the patient develop more accurate impressions of the medication.

Almutairi, Abdulaali R, Lili Zhou, Walid F Gellad, Jeannie K Lee, Marion K Slack, Jennifer R Martin, and Wei-Hsuan Lo-Ciganic. (2017) 2017. “Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-Analyses.”. Clinical Therapeutics 39 (7): 1456-1478.e36. https://doi.org/10.1016/j.clinthera.2017.05.358.

PURPOSE: The findings from the observational studies comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban).

METHODS: The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance-weighted random effects models.

FINDINGS: A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95% CI, 0.57-1.03]) and 6 observational studies (HR, 1.03 [95% CI, 0.83-1.27]). Rivaroxaban had a 20% decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95% CI, 0.67-0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95% CI, 0.59-1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95% CI, 0.66-0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95% CI, 0.77-1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10% to 71% compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32% to 69% decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95% CI, 0.40-1.49]) and 1 edoxaban RCT (HR, 0.84 [95% CI, 0.59-1.20]). Except for dabigatran, the NOACs had a 61% to 86% decreased risk of ICH and gastrointestinal bleeding.

IMPLICATIONS: Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.

Suda, Katie J, Bridget M Smith, Lauren Bailey, Walid F Gellad, Zhiping Huo, Muriel Burk, Francesca Cunningham, and Kevin T Stroupe. (2017) 2017. “Opioid Dispensing and Overlap in Veterans With Non-Cancer Pain Eligible for Medicare Part D.”. Journal of the American Pharmacists Association : JAPhA 57 (3): 333-340.e3. https://doi.org/10.1016/j.japh.2017.02.018.

OBJECTIVES: Pain is the most prevalent problem among veterans, who receive pain diagnoses 5 times more frequently than the general population. Opioids are commonly prescribed for pain, but they have potential for misuse and serious adverse events. The study objective was to evaluate opioid dispensing patterns and predictors for overlap in veterans who are eligible for Medicare Part D benefits.

METHODS: A sample of male and all female veterans aged 66 years and older without cancer in 2005-2009 was included. Overlapping days' supply of opioids were evaluated within the U.S. Department of Veterans Affairs (VA), within Part D, and in cross-system users of VA and Part D-reimbursed pharmacies during 2007-2009. Dispensing patterns were analyzed with t tests and chi-square tests. Predictors of overlap were identified with general estimating equations.

RESULTS: At least 1 opioid was dispensed to 88.5% of the sample. In 2006 after Part D implementation, 55.2% of opioids were dispensed by VA, decreasing to 44.3% in 2009 (P <0.0001). Opioids dispensed from Part D-reimbursed pharmacies had a higher frequency of overlap compared to those filled at a VA facility (P <0.0001). While overlapping days' supply for opioids filled at VA decreased, overlap increased for prescriptions filled at Part D-reimbursed pharmacies (P <0.0001). There was minimal overlap in opioids between systems, but cross-system use increased over the study period. Predictors for overlap include females, Part D enrollment, no VA medication copay, sleep disorders, psychiatric diagnoses, and substance or alcohol abuse (all P <0.01). Veterans who were Hispanic, older, and had higher incomes had lower overlap odds (all P <0.0001).

CONCLUSIONS: Opioids dispensed from Part D-reimbursed pharmacies had a higher frequency of overlapping days' supply as compared to those filled by the VA, but there was minimal overlap between systems. While overlapping opioid prescriptions filled by the VA decreased from 2007 to 2009, overlap increased for prescriptions filled at Part D-reimbursed pharmacies. Tools, such as drug monitoring programs, should be used by VA and non-VA providers to decrease opioid-related harms and misuse.