Publications by authors named "Edith A Nutescu"

127 Publications

Evaluation of point-of-care International Normalized Ratio in sickle cell disease.

Res Pract Thromb Haemost 2021 May 27;5(4):e12533. Epub 2021 May 27.

Department of Pharmacy Practice College of Pharmacy University of Illinois at Chicago Chicago IL USA.

Background: Point-of-care (POC) International Normalized Ratio (INR) measurement provides efficient monitoring of warfarin therapy; however, its reliability may be affected in patients with anemia, such as those with sickle cell disease (SCD).

Objectives: To evaluate the correlation of POC-INR to clinical laboratory INR (CL-INR) in SCD and use of a correction factor.

Patient/methods: In this retrospective study, the accuracy of POC-INR compared to CL-INR was evaluated in a cohort of patients with SCD and in a non-SCD Black cohort.

Results: Despite the difference in anemia, the SCD cohort showed a similar percentage of in-range POC-INR values as observed in the non-SCD cohort (37% vs 42%). The SCD cohort was randomly divided to form discovery and validation cohorts. In the discovery cohort, 86% of POC-INRs were in range when the POC-INRs were ˂4.0, but only 24% were in range if POC-INRs were ≥4.0. A linear regression of CL-INR versus POC-INR for POC-INR values ≥4.0 yielded a coefficient of 0.72 (95% confidence interval, 0.69-0.75); Multiplying POC-INR by this correction factor, rounded to 0.7 for ease of use in clinical practice, improved the proportion of in-range POC-INR values ≥4.0 from 24% to 100% in the SCD discovery cohort and from 19% to 95% in the SCD validation cohort. Similar findings applied to analyses of the non-SCD cohort.

Conclusions: POC-INR and CL-INR in patients with SCD are similar when POC-INR is <4.0, and the accuracy of POC-INR values ≥4.0 can be improved by applying an institution-specific correction factor.
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http://dx.doi.org/10.1002/rth2.12533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159702PMC
May 2021

Statin nonadherence in Latino and noncitizen neighborhoods in New York City, Los Angeles, and Chicago, 2012-2016.

J Am Pharm Assoc (2003) 2021 Jul-Aug;61(4):e263-e278. Epub 2021 Feb 23.

Background: Latino adults, especially immigrants without citizenship (i.e., noncitizens), experience considerable barriers to health care, including medications. Inequitable access to medications, especially statins, may exacerbate disparities in cardiovascular disease. Despite this, little is known about medication nonadherence in Latino neighborhoods, especially those with large noncitizen populations.

Objectives: To estimate nonadherence to statins in Latino neighborhoods and evaluate differences on the basis of their noncitizen population.

Methods: We conducted a retrospective cohort study among 48,161 adults who lived in predominately Latino neighborhoods in New York City, Los Angeles, and Chicago and who initiated statin therapy from January 2012 to December 2015 using IQVIA LifeLink. Statin nonadherence was defined as a proportion of days covered amounting to less than 80% over 12 months. We focused on differences between neighborhoods with high noncitizen concentrations (areas where noncitizens are at least 35% of the adult population) and other Latino neighborhoods. We examined associations using logistic regressions adjusted for individual (e.g., payment method) and neighborhood characteristics (e.g., poverty).

Results: Individuals living in neighborhoods with high noncitizen concentrations were more nonadherent to statins than those in Latino neighborhoods with fewer noncitizens (75.0% vs. 70.0%, adjusted odds ratio [aOR] 1.18, [95% CI 1.06-1.33]). These disparities were worse in New York City (77.7% vs. 69.1%, aOR 1.37, [95% CI 1.23-1.53]) and Chicago (76.1% vs. 68.8%, aOR 1.38, [95% CI 1.14-1.67]) than in Los Angeles (73.8% vs. 71.3%, aOR 1.10, [95% CI 1.01-1.20]).

Conclusion: Neighborhoods with large noncitizen populations have much higher rates of statin nonadherence than Latino neighborhoods with fewer noncitizens. These disparities were least pronounced in Los Angeles, where the county provides health care to all uninsured residents, including noncitizens without documentation to reside in the United States. Efforts to improve medication access in Latino neighborhoods should be multifocal and start by implementing state and local health care options for low-income residents, regardless of citizenship status.
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http://dx.doi.org/10.1016/j.japh.2021.01.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273086PMC
August 2021

Racial Disparities in Intravenous Bisphosphonate Use Among Older Patients With Multiple Myeloma Enrolled in Medicare.

JCO Oncol Pract 2021 03 15;17(3):e294-e312. Epub 2021 Jan 15.

University of Illinois at Chicago, Chicago, IL.

Purpose: Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM.

Methods: We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011. Patients were identified using the SEER-Medicare linked database and followed through December 2013. Cumulative incidences of IV bisphosphonate initiation and time to discontinuation among users were compared between racial and ethnic groups. In Fine and Gray competing risk models, we estimated subdistribution hazard ratios (SHRs) and 95% CIs for initiation and discontinuation.

Results: We included 14,231 eligible patients with MM (median age, 76 years; 52% male). Over a median follow-up of 23.1 months, 54% of patients received at least one IV bisphosphonate dose. Our final analytical sample included 10,456 non-Hispanic (NH) Whites, 2,267 NH Blacks, 548 Asian and Pacific islanders, and 815 Hispanic and Latino patients. A higher proportion of White patients (56.1%) newly received IV bisphosphonates after MM diagnosis compared with NH Blacks (45.4%). Compared with White patients, NH Black patients were less likely to initiate IV bisphosphonates (SHR, 0.74; 95% CI, 0.70 to 0.79) and slightly more likely to discontinue treatment (SHR, 1.10; 95% CI, 1.01 to 1.19).

Conclusion: Approximately half of the patients with MM of age ≥ 65 years did not receive IV bisphosphonates, with significant delay among racial minority groups. These findings highlight the need for improvement of IV bisphosphonate uptake in patients with MM of age ≥ 65 years.
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http://dx.doi.org/10.1200/OP.20.00479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257921PMC
March 2021

Immigration Status and Disparities in the Treatment of Cardiovascular Disease Risk Factors in the Hispanic Community Health Study/Study of Latinos (Visit 2, 2014-2017).

Am J Public Health 2020 09 16;110(9):1397-1404. Epub 2020 Jul 16.

Jenny S. Guadamuz and Martha L. Daviglus are with the Institute for Minority Health Research at the University of Illinois at Chicago. Gregory S. Calip, Edith A. Nutescu, and Dima M. Qato are with the Department of Pharmacy Systems, Outcomes, and Policy at the University of Illinois at Chicago. Ramon A. Durazo-Arvizu is with the Department of Public Health Sciences, Loyola University Chicago, Chicago, IL. Krista M. Perreira is with the Department of Social Medicine at the University of North Carolina at Chapel Hill. Linda C. Gallo and Sheila F. Castaneda are with the Department of Psychology, San Diego State University, San Diego, CA. Franklyn Gonzalez II is with the Collaborative Studies Coordinating Center, University of North Carolina at Chapel Hill.

To estimate treatment rates of high cholesterol, hypertension, and diabetes among Hispanic/Latino immigrants by immigration status (i.e., naturalized citizens, documented immigrants, or undocumented immigrants). We performed a cross-sectional analyses of the Hispanic Community Health Study/Study of Latinos (visit 2, 2014-2017). We restricted our analysis to Hispanic/Latino immigrants with high cholesterol (n = 3974), hypertension (n = 3353), or diabetes (n = 2406); treatment was defined as use of statins, antihypertensives, and antidiabetics, respectively. When compared with naturalized citizens, undocumented and documented immigrants were less likely to receive treatment for high cholesterol (38.4% vs 14.1%; prevalence ratio [PR] = 0.37 [95% confidence interval [CI] = 0.27, 0.51] and 25.7%; PR = 0.67 [95% CI = 0.58, 0.76]), hypertension (77.7% vs 57.7%; PR = 0.74 [95% CI = 0.62, 0.89] and 68.1%; PR = 0.88 [95% CI = 0.82, 0.94]), and diabetes (60.3% vs. 50.4%; PR = 0.84 [95% CI = 0.68, 1.02] and 55.8%; PR = 0.93 [95% CI = 0.83, 1.03]); the latter did not reach statistical significance. Undocumented and documented immigrants had less access to health care, including insurance coverage or a usual health care provider, than naturalized citizens. Therefore, adjusting for health care access largely explained treatment disparities across immigration status. Preventing cardiovascular disease among Hispanic/Latino immigrants should focus on undertreatment of high cholesterol, hypertension, and diabetes by increasing health care access, especially among undocumented immigrants.
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http://dx.doi.org/10.2105/AJPH.2020.305745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427208PMC
September 2020

Citizenship Status and the Prevalence, Treatment, and Control of Cardiovascular Disease Risk Factors Among Adults in the United States, 2011-2016.

Circ Cardiovasc Qual Outcomes 2020 03 10;13(3):e006215. Epub 2020 Mar 10.

Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago, College of Pharmacy (E.A.N., J.S.G., G.S.C., D.M.Q.).

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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100997PMC
March 2020

Clinical trajectories, healthcare resource use, and costs of long-term hematopoietic stem cell transplantation survivors: a latent class analysis.

J Cancer Surviv 2020 06 2;14(3):294-304. Epub 2020 Jan 2.

Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL, USA.

Purpose: To identify patterns of healthcare utilization in allogeneic and autologous hematopoietic stem cell transplantation (HSCT) recipients and evaluate factors associated with high-need and high-cost post-transplantation care.

Methods: Latent class analysis of a retrospective cohort of long-term allogeneic (n = 436) and autologous (n = 888) HSCT survivors within the Truven MarketScan database (2009-2014). We assessed factors associated with the latent classes by comparing post-transplantation healthcare utilization including inpatient admissions and length of stay, emergency room visits, specialist visits, and primary care provider visits.

Results: Four utilization classes were identified in allogeneic and autologous HSCT recipients: (i) outpatient specialist care dominant (51.8% and 57.3%), (ii) outpatient primary care dominant (10.3% and 25.7%), (iii) outpatient/inpatient balanced (20.6% and 13.5%), and (iv) inpatient dominant (17.2% and 3.5%). Mean monthly healthcare expenditures in the inpatient dominant utilization class were $41,097 and $25,556 for allogeneic and autologous survivors, respectively, which were two to five times higher compared with other classes during the 2-year post-transplantation period. Factors associated with the high utilization class were transfusion (OR = 1.87, 95% CI 1.06-3.30) and 100-day post-transplant graft-versus-host-disease (OR = 1.76, 95% CI 1.05-2.94) in allogeneic HSCT; higher baseline Charlson comorbidity index (OR = 1.45, 95% CI 1.19-1.76) in autologous HSCT.

Conclusion: Based on distinct patterns of healthcare utilization following HSCT, we identified factors associated with higher resource utilization and greater healthcare related expenditures.

Implications For Cancer Survivors: Earlier identification of high-cost and high-need HSCT long-term survivors could pave the way for clinicians to offer more continuous engagement in survivorship care delivery.
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http://dx.doi.org/10.1007/s11764-019-00842-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390707PMC
June 2020

Adherence and Persistence with DPP-4 Inhibitors Versus Pioglitazone in Type 2 Diabetes Patients with Chronic Kidney Disease: A Retrospective Claims Database Analysis.

J Manag Care Spec Pharm 2020 Jan;26(1):67-75

Department of Pharmacy Systems, Outcomes and Policy, and Center for Pharmacoepidemiology and Pharmacoeconomic Research, College of Pharmacy, University of Illinois at Chicago.

Background: Adherence and persistence with diabetes medication play an important role in glycemic control and may differ by medication class. However, there is a lack of research comparing diabetes medications in patients with renal impairment, despite the challenges and higher burden associated with managing this population.

Objective: To compare adherence and persistence among patients with type 2 diabetes mellitus (T2DM) and nondialysis chronic kidney disease (CKD) treated with dipeptidyl peptidase-4 (DPP-4) inhibitors versus pioglitazone.

Methods: This retrospective cohort study used Truven MarketScan administrative claims databases from 2009 to 2015. One-year adherence for patients with T2DM and nondialysis CKD who initiated therapy with either a DPP-4 inhibitor or pioglitazone was measured by proportion of days covered (PDC) following an initial dispensing, and PDC ≥ 0.80 was coded as adherent. Persistence was calculated as the days between the index date and last day with the index medication on hand, based on the end of the last days supply or the end of follow-up (i.e., 365 days), whichever occurred first. Multivariate logistic regression and Cox proportional hazards models were used to estimate confounder-adjusted differences between the groups for adherence and persistence.

Results: The final cohort included 9,019 patients (DPP-4 inhibitors: 7,002; pioglitazone: 2,017). In the adjusted analysis, DPP-4 inhibitor users demonstrated a 1.41 (95% CI = 1.25-1.59) higher odds of being adherent compared with pioglitazone users. Overall adjusted HR for persistence was 0.74 (95% CI = 0.69-0.79), which favored DPP-4 inhibitors compared with pioglitazone. Relative to 2010, persistence with pioglitazone decreased in 2011-2012 and then increased in 2013-2014. In the subgroup analysis, DPP-4 inhibitors first had lower (2010: OR = 0.78, 95% CI = 0.70-0.87; 2011-2012: OR = 0.60, 95% CI = 0.54-0.66) and then similar (2013-2014: OR = 1.03, 95% CI = 0.88-1.19) hazards of nonpersistence compared with pioglitazone.

Conclusions: Among patients with T2DM and nondialysis CKD, the use of DPP-4 inhibitors was associated with better adherence compared with pioglitazone. However, following the approval of generic pioglitazone and associated lower cost sharing after 2012, the magnitude of difference in adherence between the medication classes reduced. Similarly, safety warnings in 2011 and approval of generic products in 2012 may have affected pioglitazone persistence, leading to first higher and then similar hazards for nonpersistence with pioglitazone as compared with DPP-4 inhibitors. These shifts in the results for pioglitazone warrant further investigation and close monitoring of the population initiating this medication.

Disclosures: No funding was received for this study. The authors have no conflicts of interest to disclose. An abstract for this study was presented as a podium presentation at the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) 2019 Annual Meeting; May 18-22, 2019; New Orleans, LA.
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http://dx.doi.org/10.18553/jmcp.2020.26.1.67DOI Listing
January 2020

Antidiabetic drug use trends in patients with type 2 diabetes mellitus and chronic kidney disease: A cross-sectional analysis of the National Health and Nutrition Examination Survey.

J Diabetes 2020 May 22;12(5):385-395. Epub 2019 Nov 22.

Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.

Background: There is little information on medication use, trends across time, and the impact of guidelines on appropriate use of antidiabetic drugs in participants with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD).

Methods: A cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) from 2005-2016 was carried out for participants with T2DM with and without CKD. Multivariate survey-weighted regression models were used to evaluate trends in antidiabetic drug use across the time periods and CKD severity. Guideline-discordant use of metformin and glyburide were assessed among those with glomerular filtration rate and serum creatinine-based contraindications.

Results: Out of 3237 study participants with T2DM, 35.9% had CKD. Comparing 2013-2016 with 2005-2008, use of metformin (non-CKD: 69% vs 83.8%, CKD: 58.6% vs 68.2%) increased, whereas the use of sulfonylureas (non-CKD: 46.3% vs 27.2%, CKD: 54.7% vs 36.6%) and thiazolidinediones (non-CKD: 29.3% vs 3.9%, CKD: 24.6% vs 5.5%) decreased. In combined NHANES cycles and across stages of CKD severity, metformin use decreased (non-CKD, stage 1/2, stage 3, stage 4/5: 78.4%, 69.5%, 54.6%, 4.9%, respectively; P < .01), and insulin use increased (18.5%, 26.8%, 25%, 52.8%, respectively; P < .01) from non-CKD to progressed CKD. Guideline-discordant use of metformin and glyburide was observed in 8.3% and 2.8% of the participants, respectively, in 2013-2016.

Conclusions: Use of particular antidiabetic medications in patients with CKD changed noticeably over the years, most in accordance with guidelines and regulatory decisions. Gaps in quality of care still exist, which warrants increasing awareness and implementing programs to mitigate inappropriate use.
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http://dx.doi.org/10.1111/1753-0407.13003DOI Listing
May 2020

Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High-Grade Gliomas: A Nested Case-Control Study.

Pharmacotherapy 2019 09 6;39(9):921-928. Epub 2019 Aug 6.

Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.

Study Objective: Bevacizumab is used in the treatment of recurrent glioblastoma, but evidence is limited on the incidence of thromboembolic complications regarding the use of this drug in real-world settings. We evaluated the risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE) associated with the use of bevacizumab among adults diagnosed with high-grade gliomas in a commercially insured U.S.

Population:

Design: Nested case-control study.

Data Source: Truven Health MarketScan Commercial and Medicare Supplemental health claims databases (2009-2015).

Patients: A total of 2157 patients with high-grade gliomas who underwent incident (first-time) craniotomy, radiation, and concurrent temozolomide treatment between 2009 and 2015 were identified. Overall, 25 cases of ATE and 99 cases of VTE were each identified in this cohort, and each case was matched to up to 10 controls (170 for ATE and 819 for VTE) based on sex, age, quarter year of index time, and follow-up duration by using incidence density sampling without replacement from the overall cohort. Controls were at risk for the outcome of interest (ATE or VTE) at the time of case occurrence and survived at least as long as their referent case.

Measurements And Main Results: Exposure to bevacizumab was determined during inpatient or outpatient encounters between the index date (date of the incident craniotomy) and the ATE or VTE event or corresponding matched control date. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of ATE and VTE separately. A higher proportion of patients with ATE received bevacizumab compared with controls (28% vs 17%; adjusted OR 1.51, 95% CI 0.54-4.24), but this excess in odds was not statistically significant. Similarly, bevacizumab was not significantly associated with VTE (13% vs 9%; adjusted OR 1.40, 95% CI 0.71-2.75).

Conclusion: We found no significant association between the use of bevacizumab and the occurrence of thromboembolic events in patients with high-grade gliomas, although our study was limited by the small number of ATE events. Because the potential for complications from arterial thrombosis cannot be completely ruled out, further research is needed to confirm the thromboembolic safety of bevacizumab in a larger sample of patients with high-grade gliomas.
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http://dx.doi.org/10.1002/phar.2310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395667PMC
September 2019

Type 2 diabetes in adults with sickle cell disease: can we dive deeper? Response to Skinner et al.

Br J Haematol 2019 09 8;186(5):782-783. Epub 2019 May 8.

Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL, USA.

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http://dx.doi.org/10.1111/bjh.15949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706311PMC
September 2019

Differences in Warfarin Pharmacodynamics and Predictors of Response Among Three Racial Populations.

Clin Pharmacokinet 2019 08;58(8):1077-1089

Department of Biopharmaceutics, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose, Tokyo, 204-8588, Japan.

Background: Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown.

Methods: Using population PK/PD analysis, we attempted to identify predictors of S-warfarin clearance [CL(S)] and half maximal effective concentration (EC) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients.

Results: Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs. 243 and 234 mL/h, p < 0.01). EC showed a greater racial difference than CL(S) [1.03, 1.70 and 2.76 μg/mL for Asian, White and African American patients, respectively, p < 0.01). Significant predictors of INR included demographic/clinical (age, body weight, creatinine clearance and sex) and genotypic (CYP2C9*3,*8 and VKORC1 -1639G>A) factors, as well as African American ethnicity. In all three racial groups, genetic predictors of INR appeared to have greater influence than demographic/clinical predictors. Both CL(S) and EC contributed to the over-anticoagulation response to warfarin. Patients having VKORC1 -1639 G>A and/or factors associated with reduced CYP2C9 activity were more likely to have an INR ≥ 4.

Conclusions: Although there were contrasting racial differences in CL(S) and EC that impacted on the INR, the racial difference in EC was greater than that for CL(S), thus explaining the higher warfarin requirement for African American patients.
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http://dx.doi.org/10.1007/s40262-019-00745-5DOI Listing
August 2019

Similar burden of type 2 diabetes among adult patients with sickle cell disease relative to African Americans in the U.S. population: a six-year population-based cohort analysis.

Br J Haematol 2019 04 3;185(1):116-127. Epub 2019 Feb 3.

Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL, USA.

Conflicting evidence exists on the epidemiology of type 2 diabetes mellitus (T2DM) among patients with sickle cell disease (SCD). This study measured the prevalence, incidence and clinical outcomes associated with T2DM in a large US population of commercially-insured adults aged ≥20 years with SCD between 2009 and 2014. Among 7070 patients with SCD, the mean age (median) was 39 (37) years and 60·8% were female. The standardized prevalence of T2DM among patients with SCD showed a modest increase, from 15·7% to 16·5% (P trend = 0·026), and was comparable to African-American respondents to the National Health and Nutrition Examination Survey (18·2%). Over 17 024 person-years, the crude incidence rate for T2DM was 25·4 per 1000 person-years. Incident T2DM was associated with comorbid hypertension (hazard ratio [HR] = 1·45, 95% confidence interval [CI] 1·14-1·83), and dyslipidaemia (HR = 1·43, 95%CI 1·04-1·96). Compared to SCD patients without T2DM, more SCD patients with T2DM had diagnoses of nephropathy (28·0% vs. 9·5%; P < 0·001), neuropathy (17·7% vs. 5·2%; P < 0·001) and stroke (24·1% vs. 9·2%; P < 0·001). Prevalence of T2DM in SCD patients is similar to the general African American population with an increasing trend in recent years. These trends support routine screening for T2DM in aging patients with SCD, especially those with comorbid hypertension and/or dyslipidaemia.
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http://dx.doi.org/10.1111/bjh.15773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659404PMC
April 2019

The ACCOuNT Consortium: A Model for the Discovery, Translation, and Implementation of Precision Medicine in African Americans.

Clin Transl Sci 2019 05 12;12(3):209-217. Epub 2019 Feb 12.

Department of Pharmacology, Center for Pharmacogenomics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

The majority of pharmacogenomic (PGx) studies have been conducted on European ancestry populations, thereby excluding minority populations and impeding the discovery and translation of African American-specific genetic variation into precision medicine. Without accounting for variants found in African Americans, clinical recommendations based solely on genetic biomarkers found in European populations could result in misclassification of drug response in African American patients. To address these challenges, we formed the Transdisciplinary Collaborative Center (TCC), African American Cardiovascular Pharmacogenetic Consortium (ACCOuNT), to discover novel genetic variants in African Americans related to clinically actionable cardiovascular phenotypes and to incorporate African American-specific sequence variations into clinical recommendations at the point of care. The TCC consists of two research projects focused on discovery and translation of genetic findings and four cores that support the projects. In addition, the largest repository of PGx information on African Americans is being established as well as lasting infrastructure that can be utilized to spur continued research in this understudied population.
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http://dx.doi.org/10.1111/cts.12608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510376PMC
May 2019

Discontinuation and Nonadherence to Medications for Chronic Conditions after Hematopoietic Cell Transplantation: A 6-Year Propensity Score-Matched Cohort Study.

Pharmacotherapy 2019 01 4;39(1):55-66. Epub 2019 Jan 4.

Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, Illinois.

Introduction: Hematopoietic cell transplantation (HCT) is an established curative option for patients with hematological malignancies and other life-threatening conditions. Evidence on nonpersistence and nonadherence to oral medications for chronic conditions among patients following HCT is lacking.

Objectives: This study aims to examine patterns of oral medication use for chronic conditions following HCT in the U.S.

Population:

Methods: Nonpersistence and nonadherence to oral medications for diabetes, hypertension, and dyslipidemia among HCT recipients were assessed in a cohort that included 1382 autologous and 650 allogeneic HCT recipients with hematological malignancies using the Truven Health MarketScan Research Database between 2009 and 2014. Recipients of HCT were compared to propensity score-matched cancer patients receiving chemotherapy without transplantation. Multivariable Cox proportional hazards models and generalized estimating equations were used to determine characteristics associated with nonpersistence and nonadherence to oral chronic medications, respectively.

Results: Recipients of HCT had higher risks of discontinuing medication for diabetes mellitus (allogeneic HCT hazard ratio [HR] = 1.93, 95% confidence interval [CI] 1.10-3.39; autologous HCT HR = 1.49, 95% CI 1.04-2.15); hypertension (allogeneic HCT HR = 1.75, 95% CI 1.21-2.53; autologous HCT HR = 1.32, 95% CI 1.07-1.62), and dyslipidemia (allogeneic HCT HR = 2.02, 95% CI 1.39-2.93; autologous HCT, HR = 1.26, 95% CI 0.98-1.61) compared to patients treated with only chemotherapy. Lower odds of adherence to antihypertensive medications (odds ratio [OR] = 0.58, 95% CI 0.38-0.89) and to lipid-lowering medications (OR = 0.38, 95% CI 0.22-0.65) were observed in allogeneic HCT recipients compared with propensity score-matched patients who underwent chemotherapy only.

Conclusions: Poor medication persistence and adherence to chronic disease medications are common after HCT. Further research to improve long-term outcomes following HCT should include management of medication therapy for chronic comorbid conditions.
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http://dx.doi.org/10.1002/phar.2197DOI Listing
January 2019

A New Approach towards Minimizing the Risk of Misdosing Warfarin Initiation Doses.

Comput Math Methods Med 2018 13;2018:5340845. Epub 2018 May 13.

Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, IL, USA.

It is a challenge to be able to prescribe the optimal initial dose of warfarin. There have been many studies focused on an efficient strategy to determine the optimal initial dose. Numerous clinical, genetic, and environmental factors affect the warfarin dose response. In practice, it is common that the initial warfarin dose is substantially different from the stable maintenance dose, which may increase the risk of bleeding or thrombosis prior to achieving the stable maintenance dose. In order to minimize the risk of misdosing, despite popular warfarin dose prediction models in the literature which create dose predictions solely based on patients' attributes, we have taken physicians' opinions towards the initial dose into consideration. The initial doses selected by clinicians, along with other standard clinical factors, are used to determine an estimate of the difference between the initial dose and estimated maintenance dose using shrinkage methods. The selected shrinkage method was LASSO (Least Absolute Shrinkage and Selection Operator). The estimated maintenance dose was more accurate than the original initial dose, the dose predicted by a linear model without involving the clinicians initial dose, and the values predicted by the most commonly used model in the literature, the Gage clinical model.
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http://dx.doi.org/10.1155/2018/5340845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971298PMC
November 2018

Hydroxycarbamide adherence and cumulative dose associated with hospital readmission in sickle cell disease: a 6-year population-based cohort study.

Br J Haematol 2018 07 16;182(2):259-270. Epub 2018 May 16.

Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL, USA.

Sickle cell disease (SCD) is a congenital haemoglobinopathy that causes frequent acute care/emergency room visits and hospital admissions for affected individuals. Evidence from population-based studies demonstrating the role of hydroxycarbamide (HC, also termed hydroxyurea) in reducing hospital readmission rates is limited. Our objective was to describe the use of HC and its association with acute care utilization and readmission rates using a large, nationally-representative US health insurance claims database over a 6-year period between 2009 and 2014. We identified 20 721 SCD-related inpatient and acute care encounters. Patients had been exposed to HC within 6 months prior to admission in 4263 (21%) of SCD-related admission events. HC use was more common among children aged 10-17 years and young adults aged 18-29 years. HC was associated with lower 30-day all-cause readmission rates in adults treated with average daily doses ≥1 g (odds ratio [OR], 0·72, 95% confidence interval [CI] 0·52-0·99) and doses of 0·5-1 g (OR, 0·73, 95% CI 0·57-0·93), compared to HC treatment with average daily doses of <0·5 g; adherence to HC with proportion of days covered of ≥0·80 was also associated with significantly lower 30-day all-cause readmission risks (OR, 0·59, 95% CI 0·41-0·84). Optimal therapeutic dosing and adherence to HC treatment significantly reduces 30-day readmissions among patients with SCD.
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http://dx.doi.org/10.1111/bjh.15396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037608PMC
July 2018

Facilitators and Barriers to the Adoption of Pharmacogenetic Testing in an Inner-City Population.

Pharmacotherapy 2018 02 21;38(2):205-216. Epub 2018 Jan 21.

Department of Pharmacy, Systems Outcomes, and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.

Objectives: To examine the knowledge, attitudes, and interest of an inner-city population toward pharmacogenetic testing, with the primary objective of identifying facilitators and barriers toward pharmacogenetic testing; and secondary objectives of determining predictors of patient interest in pharmacogenetic testing and how much patients would pay for the test.

Methods: Patients were recruited from an Antithrombosis Clinic from March to April 2014. A cross-sectional 19-question survey was administered in person to determine patients' knowledge and awareness of pharmacogenetic testing and collect demographic information. After explaining pharmacogenetics, patients ranked their interest toward the test and answered open-ended questions that elicited facilitators and barriers toward pharmacogenetic testing and elucidated how much patients would pay for testing.

Results: A total of 120 patients (mean age 55.0 ± 14.0 years, 39.2% male, 69.2% African American) were surveyed. Facilitators included providing further information about pharmacogenetic testing; elaborating on benefits of testing to predict treatment efficacy; patients' trust in their providers to make correct genotype-guided prescribing decisions; and insurance coverage and test affordability. Barriers to testing included concerns about the negative consequences associated with test results; burden of the testing process; perceived lack of utility among elderly and those whose medications were working; privacy issues; and concerns regarding insurance coverage and test affordability. Women had 4.2 times higher adjusted odds of being interested in pharmacogenetic testing. Almost half (44.4%) of the patients with high interest in the test were willing to pay $20 or more, whereas 76.2% of patients with low interest wanted testing at no cost.

Conclusion: This study identified facilitators, such as providing additional pharmacogenetic test information, and barriers, such as perceived negative impact of the results and test utility, as issues to address when engaging an urban, largely minority population in pharmacogenetic testing. Female sex was a predictor of interest toward pharmacogenetic testing. These facilitators and barriers should be taken into consideration as pharmacogenetic testing gains widespread utility among inner-city populations.
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http://dx.doi.org/10.1002/phar.2077DOI Listing
February 2018

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

JACC Cardiovasc Interv 2018 01 1;11(2):181-191. Epub 2017 Nov 1.

Department of Medicine, University of Maryland, Baltimore, Maryland.

Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).

Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.

Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.

Results: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).

Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
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http://dx.doi.org/10.1016/j.jcin.2017.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775044PMC
January 2018

High number of newly initiated direct oral anticoagulant users switch to alternate anticoagulant therapy.

J Thromb Thrombolysis 2017 Nov;44(4):435-441

Department of Pharmacy, Systems Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood St, PHARM 227 (MC 871), Chicago, IL, 60612, USA.

Real-world evidence focusing on medication switching patterns amongst direct oral anticoagulant (DOACs) has not been well studied. The objective of this study is to evaluate patterns of prescription switching in non-valvular atrial fibrillation (NVAF) patients initiated on a DOAC and previously naïve to anticoagulation (AC) therapy. Data was obtained from Truven Health MarketScan Commercial and Medicare Supplemental database (2009-2013). AC naïve (those without prior anticoagulant use) NVAF patients initiated on a DOAC, with 6 months of continuous health plan enrollment before and after treatment initiation and maintained on continuous therapy for a minimum of 6 months were included. Of 34,022 AC naïve NVAF patients initiating a DOAC, 6613 (19.4%) patients switched from an index DOAC prescription to an alternate anticoagulant and 27,409 (80.6%) remained on the DOAC [age: 68.5 ± 11.7 vs. 67.1 ± 12.7 years, p < 0.001; males: 3781 (57.2%) vs. 17,160 (62.6%), p < 0.001]. Amongst those that switched medication, 3196 (48.3%) did so within the first 6 months of therapy. Overall, 2945 (44.5%) patients switched to warfarin, 2912 (44.0%) switched to another DOAC and 756 (11.4%) switched to an injectable anticoagulant. The highest proportion of patients switched from dabigatran to warfarin (N = 2320; 42.5%) or rivaroxaban (N = 2252; 41.3%). The median time to switch from the index DOAC to another DOAC was 309.5 days versus 118.0 days (p < 0.001) to switch to warfarin. In NVAF patients newly initiated on DOAC therapy, one in five patients switch to an alternate anticoagulant and one of every two patients do so within the first 6 months of therapy. Switching from an initial DOAC prescription to traditional anticoagulants occurs as frequently as switching to an alternate DOAC.
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http://dx.doi.org/10.1007/s11239-017-1565-2DOI Listing
November 2017

Quality of Pharmacist-Managed Anticoagulation Therapy in Long-Term Ambulatory Settings: A Systematic Review.

Ann Pharmacother 2017 Dec 22;51(12):1122-1137. Epub 2017 Jul 22.

1 University of Illinois at Chicago, Chicago, IL, USA.

Objective: To perform a systematic review to evaluate the quality of warfarin anticoagulation control in outpatient pharmacist-managed anticoagulation services (PMAS) compared with routine medical care (RMC).

Data Sources: MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, and Cochrane CENTRAL, from inception to May 2017. Search terms employed: ("pharmacist-managed" OR "pharmacist-provided" OR "pharmacist-led" OR "pharmacist-directed") AND ("anticoagulation services" OR "anticoagulation clinic" OR "anticoagulation management" OR "anticoagulant care") AND ("quality of care" OR "outcomes" OR "bleeding" OR "thromboembolism" OR "mortality" OR "hospitalization" OR "length of stay" OR "emergency department visit" OR "cost" OR "patient satisfaction").

Study Selection And Data Extraction: Criteria used to identify selected articles: English language; original studies (comments, letters, reviews, systematic reviews, meta-analyses, editorials were excluded); warfarin use; outpatient setting; comparison group present; time in therapeutic range (TTR) included as a measure of quality of anticoagulant control; study design was not a case report.

Data Synthesis: Of 177 articles identified, 25 met inclusion criteria. Quality of anticoagulation control was better in the PMAS group compared with RMC in majority of the studies (N = 23 of 25, 92.0%). Clinical outcomes were also favorable in the PMAS group as evidenced by lower or equal risk of major bleeding (N = 10 of 12, 83.3%) or thromboembolic events (N = 9 of 10, 90.0%), and lower rates of hospitalization or emergency department visits (N = 9 of 9, 100%). When reported, PMAS have also resulted in cost-savings in all (N=6 of 6, 100%) of studies.

Conclusions: Compared with routine care, pharmacist-managed outpatient-based anticoagulation services attained better quality of anticoagulation control, lower bleeding and thromboembolic events, and resulted in lower health care utilization.
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http://dx.doi.org/10.1177/1060028017721241DOI Listing
December 2017

Real-World Adherence and Persistence with Direct Oral Anticoagulants in Adults with Atrial Fibrillation.

Pharmacotherapy 2017 Oct 6;37(10):1221-1230. Epub 2017 Sep 6.

Department of Pharmacy, Systems Outcomes and Policy, University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois.

Background: Evidence of adherence and persistence patterns in anticoagulation (AC) therapy comparing treatment-naïve and non-naïve patients is lacking. The objective of this study was to evaluate patterns of medication adherence and persistence in a real-world setting among AC-naïve and AC-experienced patients with atrial fibrillation (AF) who were treated with direct oral anticoagulants (DOACs).

Methods: AF patients newly initiating a DOAC with a minimum of 6 months of continuous health plan enrollment pre and postindex date (first DOAC prescription) were identified from the Truven Health MarketScan Commercial and Medicare Supplemental databases (2009-2013). DOAC adherence (proportion of days covered [PDC]), persistence, and predictors of adherence were assessed at 6 and 12 months postindex.

Results: Of 66,090 AF patients included, 46.6% (n=30,826) were AC naïve and 53.4% (n=35,264) were AC experienced (age: 66.9 ± 12.7 vs 70.4 ± 11.4 yrs, p<0.001; male: n=19,132 [62.1%] vs n=21,691 [61.5%], p=0.14, respectively). A majority of patients received dabigatran as their index DOAC (n=49,210; 74.5%). The mean PDC in AC-naïve versus AC-experienced patients at 6 and 12 months of follow-up was 72.3% versus 83.3% (p<0.001) and 63.7% versus 79.9% (p<0.001), respectively. Persistence with DOAC therapy in AC-naïve and AC-experienced patients at 6 and 12 months ranged from 59.3% and 76.3% (p<0.0001) to 31.6% and 50.2% (p<0.0001), respectively. Predictors of higher DOAC adherence were older age and higher number of concomitant medications. Predictors of lower adherence were higher number of comorbidities and AC-naïve user status.

Conclusion: Medication adherence and persistence with DOACs declined over time and both were suboptimal and lower (at 6 and 12 mo postindex) in AC-naïve compared to AC-experienced patients. These findings can help target future strategies or interventions for patient education and long-term AC management especially in those patients naïve to DOAC therapy. Future investigation should examine potential reasons for differences in DOAC adherence and persistence between AC-experienced versus AC-naïve patients and the implications for patient outcomes.
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http://dx.doi.org/10.1002/phar.1989DOI Listing
October 2017

Correlations between the enantio- and regio-selective metabolisms of warfarin.

Pharmacogenomics 2017 Jan 20;18(2):133-142. Epub 2016 Dec 20.

Department of Pharmacotherapy, Meiji Pharmaceutical University, Tokyo, Japan.

Aim: To clarify whether the activities of multiple CYPs associated with warfarin metabolism would be correlated with each other.

Methods: Oral clearances (CLpo) of warfarin enantiomers were estimated in 378 Chinese, Caucasians and African-Americans. The partial metabolic clearances (CLm) for 7-hydroxywarfarin enantiomers were also measured. In addition, CLpo and CLm were determined in a patient on warfarin and rifampicin.

Results: Correlations between CLpo for warfarin enantiomers existed across the three populations. In addition, there was a significant correlation between the CLm for 7-hydroxylation of warfarin enantiomers. Under induced conditions by rifampicin, there were significant correlations between the enantio- and regio-selective metabolisms of warfarin.

Conclusion: Metabolic activities of CYP2C9, CYP1A2 and CYP3A4 may be regulated by common transcriptional mechanism(s).
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http://dx.doi.org/10.2217/pgs-2016-0149DOI Listing
January 2017

Implementation of inpatient models of pharmacogenetics programs.

Am J Health Syst Pharm 2016 Dec;73(23):1944-1954

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL.

Purpose: The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided drug therapy in pharmacogenetics programs at three institutions is highlighted.

Summary: Pharmacists are well positioned to assume important roles in facilitating the clinical use of genetic information to optimize drug therapy given their expertise in clinical pharmacology and therapeutics. Pharmacists have assumed important roles in implementing inpatient pharmacogenetics programs. This includes programs designed to incorporate genetic test results to optimize antiplatelet drug selection after percutaneous coronary intervention and personalize warfarin dosing. Pharmacist involvement occurs on many levels, including championing and leading pharmacogenetics implementation efforts, establishing clinical processes to support genotype-guided therapy, assisting the clinical staff with interpreting genetic test results and applying them to prescribing decisions, and educating other healthcare providers and patients on genomic medicine. The three inpatient pharmacogenetics programs described use reactive versus preemptive genotyping, the most feasible approach under the current third-party payment structure. All three sites also follow Clinical Pharmacogenetics Implementation Consortium guidelines for drug therapy recommendations based on genetic test results.

Conclusion: With the clinical emergence of pharmacogenetics into the inpatient setting, it is important that pharmacists caring for hospitalized patients are well prepared to serve as experts in interpreting and applying genetic test results to guide drug therapy decisions. Since genetic test results may not be available until after patient discharge, pharmacists practicing in the ambulatory care setting should also be prepared to assist with genotype-guided drug therapy as part of transitions in care.
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http://dx.doi.org/10.2146/ajhp150946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359627PMC
December 2016

Upper-Extremity Deep-Vein Thrombosis: A Retrospective Cohort Evaluation of Thrombotic Risk Factors at a University Teaching Hospital Antithrombosis Clinic.

Ann Pharmacother 2016 08 17;50(8):637-44. Epub 2016 May 17.

University of Illinois at Chicago, IL, USA.

Background: Upper-extremity deep-vein thrombosis (UEDVT) causes significant morbidity and mortality and is not well characterized in the existing literature, particularly in underrepresented minorities such as African Americans.

Objective: To describe the characteristics of a cohort of patients with UEDVT seen at an urban academic medical center.

Methods: This was a retrospective cohort study among patients with a confirmed UEDVT at the University of Illinois Hospital and Health Sciences System between 1996 and 2011. Patients were identified by ICD-9 code for UEDVT. Variables collected include thrombotic risk factors and outcomes, including recurrent thrombosis and bleeding.

Results: We identified 229 patients with UEDVT; 71% were African American, and 11% were diagnosed with sickle cell disease. The average number of UEDVT risk factors was 4.40 ± 1.5, the most common being central venous catheter (CVC) use (178, 78%). In the year following UEDVT, 13% experienced recurrent thrombosis, and 6% experienced major bleeding. Of 181 patients receiving warfarin after an UEDVT, 36% of international normalized ratio (INR) values were therapeutic. Patients with sickle cell disease had a lower proportion of INRs within the target range (25% vs 38%, P < 0.01), and were more likely to be lost to follow-up (67% vs 46%, P = 0.05) and experience a recurrent thrombotic event (29% vs 11%, P = 0.02).

Conclusion: A CVC is the most common risk factor for UEDVT; however, patients with sickle cell disease demonstrate additional unique demographics and risk factors. Patients included in this underrepresented demographic cohort had a low quality of anticoagulation control, particularly those with sickle cell disease.
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http://dx.doi.org/10.1177/1060028016649601DOI Listing
August 2016

Erratum to: Pharmacology of anticoagulants used in the treatment of venous thromboembolism.

J Thromb Thrombolysis 2016 08;42(2):296-311

University of Washington School of Pharmacy, Seattle, WA, USA.

Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE.
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http://dx.doi.org/10.1007/s11239-016-1363-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969935PMC
August 2016

Pharmacology of anticoagulants used in the treatment of venous thromboembolism.

J Thromb Thrombolysis 2016 Jan;41(1):15-31

University of Washington School of Pharmacy, Seattle, WA, USA.

Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE.
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http://dx.doi.org/10.1007/s11239-015-1314-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715843PMC
January 2016

The evolving role of dabigatran etexilate in clinical practice.

Expert Opin Pharmacother 2015 6;16(13):2053-72. Epub 2015 Aug 6.

University of Illinois at Chicago College of Pharmacy , 833 South Wood Street, Suite 164, MC 886, Chicago, IL 60612 , USA.

Introduction: Stroke and venous thromboembolism (VTE) affect millions of patients. The vitamin K antagonist, warfarin, has been the main oral anticoagulant used to treat these conditions despite many limitations associated with its use. Recently, multiple novel oral anticoagulants have been approved and are reshaping how patients with atrial fibrillation (AF) at risk of stroke and patients with VTE are treated. The direct thrombin inhibitor, dabigatran etexilate , is among these novel agents that have been developed to overcome limitations with warfarin.

Areas Covered: In this article, authors describe the pharmacokinetic and pharmacodynamic properties of dabigatran etexilate and summarize the clinical evidence and controversy surrounding its use in the US, Canada and Europe.

Expert Opinion: Dabigatran has demonstrated similar efficacy and safety to enoxaparin for VTE prevention in patients undergoing hip and knee arthroplasty, and to warfarin for the treatment of VTE. Dabigatran (110 mg) is noninferior and dabigatran (150 mg) is superior to warfarin for stroke prevention in patients with nonvalvular AF, with a lower rate of intracranial hemorrhage reported at both doses. Apixaban, rivaroxaban and edoxaban provide alternate anticoagulant options to dabigatran. While there are many similarities, there are also significant differences to consider in agent selection based on patient-specific characteristics.
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http://dx.doi.org/10.1517/14656566.2015.1074179DOI Listing
November 2015

Daily costs of hospitalization in non-valvular atrial fibrillation patients treated with anticoagulant therapy.

J Med Econ 2015 26;18(12):1041-9. Epub 2015 Aug 26.

d d The University of Illinois at Chicago College of Pharmacy , Chicago , IL , USA.

Background: Atrial fibrillation (AF) is the most common cardiac rhythm disturbance in the US, with an estimated prevalence of 2.7-6.1 million persons in 2010.

Objective: This study evaluates the progression of daily hospitalization costs among non-valvular atrial fibrillation (NVAF) patients treated with anticoagulant therapy.

Methods: A claims analysis was conducted with Premier Perspective Comparative Hospital Database records from January 2009-March 2013. Patients of 18 years or older who were diagnosed with NVAF and used anticoagulant therapy were studied. Treatment patterns and mean daily costs of hospitalization per patient as well as total costs of hospitalization were reported. Comparisons of mean daily costs with those of the previous day were presented to identify statistical cost differences between hospitalization days.

Results: A total of 375,560 patients were identified; 67,017 with AF as admitting/primary diagnosis, and 308,543 with AF as a secondary diagnosis. The mean age of the overall population, primary AF diagnosis cohort, and secondary AF diagnosis cohort was 73.8, 67.9, and 75.0 years, while their proportion of females was 46.3%, 45.6%, and 46.5%, respectively. The mean length of stay was 6.8 days, 3.7 days, and 7.5 days for the overall population, the primary AF diagnosis cohort, and the secondary AF diagnosis cohort, respectively. For all cohorts, mean daily costs stabilized on the third day (overall population: $2103; primary AF diagnosis cohort: $1505; secondary AF diagnosis cohort: $2208).

Limitations: Claims data may have contained inaccuracies or omissions in coded procedures, diagnoses, or pharmacy claims.

Conclusion: The study showed that daily hospitalization costs for NVAF patients stabilized on the third day of hospitalization and that any reduction or prolongation in hospital length of stay could have a significant impact on the cost burden associated with AF.
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http://dx.doi.org/10.3111/13696998.2015.1074583DOI Listing
October 2016

Relationship between time spent at extreme International Normalized Ratios and time in therapeutic range with bleeding and thrombosis in warfarin-treated patients.

Am J Health Syst Pharm 2015 Jul;72(14):1188-94

Ashley L. Barta, Pharm.D., is Clinical Pharmacist, Sanford USD Medical Center, Sioux Falls, SD; when this project was conducted she was Postgraduate Year 1 Resident, Sanford USD Medical Center. Edith A. Nutescu, Pharm.D., is Associate Professor, Department of Pharmacy Systems Outcomes and Policy, and Co-Director, Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago College of Pharmacy, Chicago. Paul A. Thompson, Ph.D., is Director, Methodology and Data Analysis Center, and Professor, Department of Pediatrics, Sanford School of Medicine, Sanford Research, Sioux Falls. Henry I. Bussey, Pharm.D., is President and Senior Editor, ClotCare.org, San Antonio, TX, and President, Genesis Clinical Research, San Antonio. Michael P. Gulseth, Pharm.D., BCPS, FASHP, is Program Director for Anticoagulation Services, Sanford USD Medical Center, and Adjunct Assistant Professor, College of Pharmacy, South Dakota State University, Sioux Falls.

Purpose: The relationship between the time spent at extreme International Normalized Ratios (INRs) and the time in the therapeutic range (TTR) with bleeding and thrombosis in warfarin-treated patients was examined.

Methods: Consecutive patients treated with warfarin for atrial fibrillation or for venous thrombosis who were managed by the anticoagulation management service or adult internal medicine clinic of a large, tertiary care, integrated health system between June 1, 2011, and October 9, 2012, were eligible for study inclusion. Data collected for the outcomes analysis included INRs and dates; current use of aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, or nonsteroidal antiinflammatory drugs; and any clinically significant bleeding or thrombosis events identified.

Results: In the 837 patients who met the inclusion criteria, 636.5 patient-years of therapy were provided, of which 14.4 patient-years (2.26% of time) were spent at INRs of <1.5; 2.9 patient-years of therapy (0.45% of time) were spent at INRs of >4.5. The patient population had a mean individual TTR of 65%. The percentage of time at an INR of >4.5 was positively associated with an increased risk of major bleeding (p = 0.0085). The percentage of time spent with an INR of <1.5 was not associated with a significant increase in the risk of thrombosis.

Conclusion: The percentage of time spent with an INR of >4.5 was associated with an increased risk of major bleeding in patients receiving warfarin for atrial fibrillation or for venous thrombosis at two outpatient clinics. The relationships between thrombosis risk and the TTR or the time spent at an INR of <1.5 were not significant, but the thromboembolic event rate was unusually low, as was the time spent at an INR of <1.5.
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http://dx.doi.org/10.2146/ajhp140752DOI Listing
July 2015

Factors influencing pharmacokinetics of warfarin in African-Americans: implications for pharmacogenetic dosing algorithms.

Pharmacogenomics 2015 ;16(3):217-25

Department of Biopharmaceutics, Meiji Pharmaceutical University, Kiyose, Tokyo 204 8588, Japan.

Aim: This study attempted to identify predictors of S-warfarin clearance (CL[S]) and to make a pharmacokinetic evaluation of genotype-based dosing algorithms in African-Americans.

Methods: Using plasma S-warfarin concentration (Cp[S]) at a steady state and eight SNPs previously shown to influence warfarin dose in African-Americans, CL(S) and its predictors were estimated by population pharmacokinetic analysis in 60 African-Americans. The time courses of Cp(S) following either the loading dose or maintenance dose were simulated using the population pharmacokinetic estimates.

Results: CYP2C9*8 and body surface area or body weight were predictors of CL(S) (-30 and -5% per -0.1 m(2)/-10 kg reduction in CL[S], respectively) in African-Americans. Simulations of Cp(S) showed that Cp(S) at steady state was 1.4-times higher in patients with CYP2C9*8 than in those with CYP2C9*1/*1, irrespective of the algorithm for loading dose or maintenance dose.

Conclusion: African-Americans possess independent predictors of CL(S), possibly leading to a prediction error of any dosing algorithm that excludes African-specific variant(s). Original submitted 3 September 2014; Revision submitted 3 November 2014.
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http://dx.doi.org/10.2217/pgs.14.160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347085PMC
November 2015
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