Implementation of pharmacogenomics into inpatient general medicine.

Pharmacogenomics is a crucial piece of personalized medicine. Preemptive pharmacogenomic testing is only used sparsely in the inpatient setting and there are few models to date for fostering the adoption of pharmacogenomic treatment in the inpatient setting. We created a multi-institutional project in Chicago to enable the translation of pharmacogenomics into inpatient practice. We are reporting our implementation process and barriers we encountered with solutions. This study, 'Implementation of Point-of-Care Pharmacogenomic Decision Support Accounting for Minority Disparities', sought to implement pharmacogenomics into inpatient practice at three sites: The University of Chicago, Northwestern Memorial Hospital, and the University of Illinois at Chicago. This study involved enrolling African American adult patients for preemptive genotyping across a panel of actionable germline variants predicting drug response or toxicity risk. We report our approach to implementation and the barriers we encountered engaging hospitalists and general medical providers in the inpatient pharmacogenomic intervention. Our strategies included: a streamlined delivery system for pharmacogenomic information, attendance at hospital medicine section meetings, use of physician and pharmacist champions, focus on hospitalists' care and optimizing system function to fit their workflow, hand-offs, and dealing with hospitalists turnover. Our work provides insights into strategies for the initial engagement of inpatient general medicine providers that we hope will benefit other institutions seeking to implement pharmacogenomics in the inpatient setting.

Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.

Background and Objectives: Warfarin and a skeletal muscle relaxant are co-treatments in nearly a quarter-million annual United States (US) office visits. Despite international calls to minimize patient harm arising from anticoagulant drug interactions, scant data exist on clinical outcomes in real-world populations. We examined effects of concomitant use of warfarin and individual muscle relaxants on rates of hospitalization for thromboembolism among economically disadvantaged persons. Materials and Methods: Using 1999−2012 administrative data of four US state Medicaid programs, we conducted 16 retrospective self-controlled case series studies: half included concomitant users of warfarin + one of eight muscle relaxants; half included concomitant users of an inhaled corticosteroid (ICS) + one of eight muscle relaxants. The ICS analyses served as negative control comparisons. In each study, we calculated incidence rate ratios (IRRs) comparing thromboembolism rates in the co-exposed versus warfarin/ICS-only exposed person-time, adjusting for time-varying confounders. Results: Among ~70 million persons, we identified 8693 warfarin-treated subjects who concomitantly used a muscle relaxant, were hospitalized for thromboembolism, and met all other inclusion criteria. Time-varying confounder-adjusted IRRs ranged from 0.31 (95% confidence interval: 0.13−0.77) for metaxalone to 3.44 (95% confidence interval: 1.53−7.78) for tizanidine. The tizanidine finding was robust after quantitatively adjusting for negative control ICS findings, and in numerous prespecified secondary analyses. Conclusions: We identified a potential >3-fold increase in the rate of hospitalized thromboembolism in concomitant users of warfarin + tizanidine vs. warfarin alone. Alternative explanations for this finding include confounding by indication, a native effect of tizanidine, or chance.

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

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.

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).

Objectives. 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).Methods. 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.Results. 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.Conclusions. 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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Pharmacology of anticoagulants used in the treatment of venous thromboembolism.

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.

Poor warfarin dose prediction with pharmacogenetic algorithms that exclude genotypes important for African Americans.

OBJECTIVES: Recent clinical trial data cast doubt on the utility of genotype-guided warfarin dosing, specifically showing worse dosing with a pharmacogenetic versus clinical dosing algorithm in African Americans. However, many genotypes important in African Americans were not accounted for. We aimed to determine whether omission of the CYP2C9*5, CYP2C9*6, CYP2C9*8, CYP2C9*11 alleles and rs12777823 G > A genotype affects performance of dosing algorithms in African Americans. METHODS: In a cohort of 274 warfarin-treated African Americans, we examined the association between the CYP2C9*5, CYP2C9*6, CYP2C9*8, CYP2C9*11 alleles and rs12777823 G > A genotype and warfarin dose prediction error with pharmacogenetic algorithms used in clinical trials. RESULTS: The http://www.warfarindosing.org algorithm overestimated doses by a median (interquartile range) of 1.2 (0.02-2.6) mg/day in rs12777823 heterozygotes (P<0.001 for predicted vs. observed dose), 2.0 (0.6-2.8) mg/day in rs12777823 variant homozygotes (P = 0.004), and 2.2 (0.5-2.9) mg/day in carriers of a CYP2C9 variant (P < 0.001). The International Warfarin Pharmacogenetics Consortium (IWPC) algorithm underdosed warfarin by 0.8 (-2.3 to 0.4) mg/day for patients with the rs12777823 GG genotype (P < 0.001) and overdosed warfarin by 0.7 (-0.4 to 1.9) mg/day in carriers of a variant CYP2C9 allele (P = 0.04). Modifying the http://www.warfarindosing.org algorithm to adjust for variants important in African Americans led to better dose prediction than either the original http://www.warfarindosing.org (P < 0.01) or IWPC (P < 0.01) algorithm. CONCLUSION: These data suggest that, when providing genotype-guided warfarin dosing, failure to account for variants important in African Americans leads to significant dosing error in this population.

Integrating electronic health records in the delivery of optimized anticoagulation therapy.

Integration of accepted practice standards into electronic health record systems can facilitate standardization of anticoagulation care delivery and result in improved anticoagulation safety. However, the majority of commonly used electronic health record systems are lacking the specialized features necessary for optimal anticoagulation management. The Task Force on Electronic Health Records of the New York State Anticoagulation Coalition provides such a Consensus Statement in this issue of the journal. The Anticoagulation Forum endorses these recommendations and advises the electronic health record industry and health information technology programmers at the institutional level to adopt these recommendations in a comprehensive and timely manner.

Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study.

BACKGROUND: VKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. METHODS: We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 -1639G→A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5×10(-8) in the discovery cohort and p<0·0038 in the replication cohort. FINDINGS: The discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1·51×10(-8)). This association was confirmed in the replication cohort (p=5·04×10(-5)); analysis of the two cohorts together produced a p value of 4·5×10(-12). Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6·92 mg/week and those homozygous 9·34 mg/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement). INTERPRETATION: A novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3. Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population. FUNDING: National Institutes of Health, American Heart Association, Howard Hughes Medical Institute, Wisconsin Network for Health Research, and the Wellcome Trust.

Socioecologic Factors and Racial Differences in Breast Cancer Multigene Prognostic Scores in US Women.

Importance: Disproportionately aggressive tumor biology among non-Hispanic Black women with early-stage, estrogen receptor (ER)-positive breast cancer contributes to racial disparities in breast cancer mortality. It is unclear whether socioecologic factors underlie racial differences in breast tumor biology. Objective: To examine individual-level (insurance status) and contextual (area-level socioeconomic position and rural or urban residence) factors as possible mediators of racial and ethnic differences in the prevalence of ER-positive breast tumors with aggressive biology, as indicated by a high-risk gene expression profile. Design, Setting, and Participants: This retrospective cohort study included women 18 years or older diagnosed with stage I to II, ER-positive breast cancer between January 1, 2007, and December 31, 2015. All data analyses were conducted between December 2022 and April 2023. Main Outcomes and Measures: The primary outcome was the likelihood of a high-risk recurrence score (RS) (≥26) on the Oncotype DX 21-gene breast tumor prognostic genomic biomarker. Results: Among 69 139 women (mean [SD] age, 57.7 [10.5] years; 6310 Hispanic [9.1%], 274 non-Hispanic American Indian and Alaskan Native [0.4%], 6017 non-Hispanic Asian and Pacific Islander [8.7%], 5380 non-Hispanic Black [7.8%], and 51 158 non-Hispanic White [74.0%]) included in our analysis, non-Hispanic Black (odds ratio [OR], 1.33; 95% CI, 1.23-1.43) and non-Hispanic American Indian and Alaska Native women (OR, 1.38; 95% CI, 1.01-1.86) had greater likelihood of a high-risk RS compared with non-Hispanic White women. There were no significant differences among other racial and ethnic groups. Compared with non-Hispanic White patients, there were greater odds of a high-risk RS for non-Hispanic Black women residing in urban areas (OR, 1.35; 95% CI, 1.24-1.46), but not among rural residents (OR, 1.05; 95% CI, 0.77-1.41). Mediation analysis demonstrated that lack of insurance, county-level disadvantage, and urban vs rural residence partially explained the greater odds of a high-risk RS among non-Hispanic Black women (proportion mediated, 17%; P < .001). Conclusions and Relevance: The findings of this cohort study suggest that the consequences of structural racism extend beyond inequities in health care to drive disparities in breast cancer outcome. Additional research is needed with more comprehensive social and environmental measures to better understand the influence of social determinants on aggressive ER-positive tumor biology among racial and ethnic minoritized women from disadvantaged and historically marginalized communities.

Delivery of optimized inpatient anticoagulation therapy: consensus statement from the anticoagulation forum.

OBJECTIVE: To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. DATA SOURCES: The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/ organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/ drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. STUDY SELECTION AND DATA EXTRACTION: Because of this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of patients receiving anticoagulation therapy. DATA SYNTHESIS: Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in 8 key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education, (7) care transitions, and (8) outcomes. Recommendations are intended to inform the development of coordinated care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized inpatient anticoagulation therapy are intended to apply to all clinicians involved in the care of hospitalized patients receiving anticoagulation therapy. CONCLUSIONS: Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national organizations have introduced initiatives to reduce the likelihood of patient harm associated with the use of anticoagulants. Health care organizations are under increasing pressure to develop systems to ensure the safe and effective use of anticoagulants in the inpatient setting. This document provides consensus guidelines for anticoagulant therapy in the inpatient setting and serves as a companion document to prior guidelines relevant for outpatients.

Reversal of Oral Anticoagulants: A Survey of Contemporary Practice Trends (ReACT).

This study evaluated practice patterns and factors influencing treatment decisions regarding urgent or emergent reversal of oral anticoagulants (OACs). A 30-question survey was electronically distributed to anticoagulation members of the Anticoagulation Forum. Questions were designed to capture practice trends in the reversal of warfarin, factor Xa inhibitors, and factor IIa inhibitors. Continuous and categorical data were analyzed to generate descriptive statistics. Open-ended questions were summarized by thematic categories. 173 responses were collected most from US-based pharmacists with direct patient care responsibilities. The majority of the respondents' institutions (90.2%) utilized a guideline or protocol for OACs reversal. Vitamin K (91.3%), activated charcoal (80.4%), and fresh frozen plasma (72.8%) were the most common reversal agents on formulary without restrictions. Most institutions (87.0%) reported having 4-factor prothrombin complex concentrate (4F-PCC) and idarucizumab on formulary, but most commonly (52.2%) with restrictions. Andexanet alfa was only reported on formulary at 35.9% of institutions. In contrast to current guideline recommendations, vitamin K (98.8%) was preferred over 4F-PCC and 4F-PCC (71.6%) was preferred over andexanet alfa as first-line agents used to reverse warfarin and factor Xa inhibitors, respectively. Weight-based dosing strategies for 4F-PCC were commonly utilized for different reversals (41.2%-59.4%). Cost, efficacy, and safety of 4F-PCC were identified as top facilitators and barriers for 4F-PCC adoption in practice. Our findings revealed that guideline recommendations for reversal of warfarin and factor Xa and IIa inhibitors are not followed by a majority of institutions. Studies are needed to investigate strategies to overcome barriers for implementing and following guideline recommendations.

The Relationship Between Signature Time and Functional Health Literacy: Results from a Prospective Study of an Urban Low-Income Population Receiving Long-Term Anticoagulation.

INTRODUCTION: Low health literacy (HL) is consistently associated with worse health outcomes. Routine clinical screening with available instruments is impractical because of added time and effort. Prior findings suggested that signature time may be a reliable alternative measure of HL among general medicine patients. METHODS: Our aim was to assess the screening performance of signature time and explore optimal thresholds for identifying patients with limited HL in a chronically anticoagulated population. English-speaking patients receiving long-term anticoagulation therapy were recruited. HL was assessed using the Short Test of Functional Health Literacy in Adults (STOFHLA). Signature time was measured using a stopwatch. Logistic regression models and receiver-operating characteristic (ROC) curves were used to evaluate the association and accuracy of signature time compared to HL, respectively. RESULTS: Of 139 enrolled patients, mean age was 60.1 years, 70.5% were African-American, 48.9% reported < $25,000 income, and 27.3% had marginal or inadequate HL. Overall, median time to sign was 6.1 s. Signature time was longest with inadequate HL (median 9.5 s) compared to adequate HL (5.7 s; p < 0.01). Longer signature time was significantly associated with lower HL after adjusting for age and education (aOR 0.77, 95% CI: 0.68-0.88, p < 0.01). Signature time demonstrated high accuracy (area under the curve [AUC] > 0.8) in identifying HL levels. Thresholds of 5.1 s and 9.0 s showed appropriate screening performance in distinguishing patients with adequate vs. marginal and marginal vs. inadequate HL, respectively. CONCLUSION: Signature time demonstrated strong screening performance and may offer a quick and practical approach to assessing HL among patients receiving long-term anticoagulation management.

The Role of Global and Local Ancestry on Clopidogrel Response in African Americans.

Pharmacogenomics has long lacked dedicated studies in African Americans, resulting in a lack of indepth data in this populations. The ACCOuNT consortium has collected a cohort of 167 African American patients on steady state clopidogrel with the goal of discovering population specific variation that may contribute to the response of this anti-platelet agent. Here we analyze the role of both global and local ancestry on the clinical phenotypes of P2Y12 reaction units (PRU) and high on-treatment platelet reactivity (HTPR) in this cohort. We found that local ancestry at the TSS of three genes, IRS-1, ABCB1 and KDR were nominally associated with PRU, and local ancestry-adjusted SNP association identified variants in ITGA2 associated to increased PRU. These finding help to explain the variability in drug response seen in African Americans, especially as few studies on genes outside of CYP2C19 has been conducted in this population.