CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. METHODS AND RESULTS: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P<0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P=0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups. CONCLUSIONS: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.

Implementation of an eFAST guideline and teaching to improve documentation practices and saving of ultrasound images.

OBJECTIVES: To investigate whether implementation of a hospital-based Extended Focused Assessment with Sonography in Trauma (eFAST) guideline and teaching improved documentation and saving of images. METHODS: A retrospective cohort study was conducted on trauma patients aged ≥16 years presenting to St Vincent's Hospital Sydney Emergency Department over two, three-month periods in 2023. RESULTS: Guideline and teaching implementation resulted in statistically significant improvement in documentation on the Trauma Response Form, 85% (113/133) to 93% (120/129), odds ratio (OR) 2.4 (95% confidence interval [CI] = 1.03-5.40), P = 0.04, and images saved, 4% (5/133) to 21% (27/129), OR 6.7 (95% CI = 2.5-18.2), P < 0.001. CONCLUSIONS: Developing an eFAST Standard of Care Guideline and education was associated with improvements in documentation and saving of images to ultrasound machines.

Effectiveness of Clopidogrel vs Alternative P2Y12 Inhibitors Based on the ABCD-GENE Score.

BACKGROUND: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear. OBJECTIVES: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y12 inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI). METHODS: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y12 inhibitor treatment were included. The primary outcome was major atherothrombotic events (MAE) within 1 year after PCI. Cox regression was performed to assess event risk in clopidogrel-treated (reference) vs alternatively treated patients, with stabilized inverse probability weights derived from exposure propensity scores after stratifying by ABCD-GENE score and further by CYP2C19 loss-of-function (LOF) genotype. RESULTS: Among patients with scores <10 (n = 3,200), MAE was not different with alternative therapy vs clopidogrel (weighted HR: 0.89; 95% CI: 0.65-1.22; P = 0.475). The risk for MAE also did not significantly differ by treatment among patients with scores ≥10 (n = 1,135; weighted HR: 0.75; 95% CI: 0.51-1.11; P = 0.155). Among CYP2C19 LOF allele carriers, MAE risk appeared lower with alternative therapy in both the group with scores <10 (weighted HR: 0.50; 95% CI: 0.25-1.01; P = 0.052) and the group with scores ≥10 (weighted HR: 0.48; 95% CI: 0.29-0.80; P = 0.004), while there was no difference in the group with scores <10 and no LOF alleles (weighted HR: 1.03; 95% CI: 0.70-1.51; P = 0.885). CONCLUSIONS: These data support the use of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABCD-GENE score, while clopidogrel is as effective as alternative therapy in non-LOF patients with scores <10.

Metabolomic Association and Risk Prediction With Heart Failure in Older Adults.

BACKGROUND: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults. METHODS: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication. RESULTS: Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05). CONCLUSIONS: Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.

Cardiomyocyte Alpha-1A Adrenergic Receptors Mitigate Postinfarct Remodeling and Mortality by Constraining Necroptosis.

Clinical studies have shown that α1-adrenergic receptor antagonists (α-blockers) are associated with increased heart failure risk. The mechanism underlying that hazard and whether it arises from direct inhibition of cardiomyocyte α1-ARs or from systemic effects remain unclear. To address these issues, we created a mouse with cardiomyocyte-specific deletion of the α1A-AR subtype and found that it experienced 70% mortality within 7 days of myocardial infarction driven, in part, by excessive activation of necroptosis. We also found that patients taking α-blockers at our center were at increased risk of death after myocardial infarction, providing clinical correlation for our translational animal models.

Race-ethnicity and sex differences in 1-year survival following percutaneous coronary intervention among Medicare fee-for-service beneficiaries.

RATIONALE: Existing literature describing differences in survival following percutaneous coronary intervention (PCI) by patient sex, race-ethnicity and the role of socioeconomic characteristics (SEC) is limited. AIMS AND OBJECTIVES: Evaluate differences in 1-year survival after PCI by sex and race-ethnicity, and explore the contribution of SEC to observed differences. METHODS: Using a 20% sample of Medicare claims data for beneficiaries aged 65+, we identified fee-for-service patients who received PCI from 2007 to 2015. We performed logistic regression to assess how sex and race-ethnicity relate to procedural indication, inpatient versus outpatient setting, and 1-year mortality. We evaluated whether these relationships are moderated by sequentially controlling for factors including age, comorbidities, presence of acute myocardial infarction (AMI), county SEC, medical resource availability and inpatient versus outpatient procedural status. RESULTS: We identified 300,491 PCI procedures, of which 94,863 (31.6%) were outpatient. There was a significant transition to outpatient PCI during the study period, especially for men compared with women and White patients compared with Black patients. Black patients were 3.50 percentage points (p < 0.001) and women were 3.41 percentage points (p < 0.001) more likely than White and male patients to undergo PCI at the time of AMI, which typically occurs in the inpatient setting. Controlling for age and calendar year, Black patients were 2.87 percentage points more likely than non-Hispanic White patients to die within 1 year after PCI. After controlling for Black-White differences in comorbidities, the differences in 1-year mortality decreased to 0.95 percentage points, which then became nonsignificant when further controlling for county resources and state of residence. CONCLUSION: Women were more likely to experience PCI in the setting of AMI and had less transition to outpatient care during the period. Black patients experienced higher 1-year mortality following PCI, which is explained by differences in baseline comorbidities, county medical resources, and state of residence.

Multiple anthelmintic drug resistant Ancylostoma caninum in foxhounds.

Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to all classes of anthelmintics, little is known about the frequency and extent of this anthelmintic resistance. The study aim was to evaluate the efficacy of three commercial anthelmintic products in the treatment of foxhound dogs with a history of persistent A. caninum infections. In the first phase of this study, 35 foxhounds were randomly divided into three treatment groups: moxidectin/imidacloprid (MI), pyrantel pamoate/febantel/praziquantel (PFP), and emodepside/praziquantel (EP). Fecal samples were collected on day 0, 11, and 33 post-treatment (PT), and hookworm eggs were quantified using the mini-FLOTAC technique with a multiplication factor of 5 eggs per gram (EPG). The fecal egg count reduction (FECR) on day 11 PT was 65% (95% CI: 62%-68%) for MI, 69% (95% CI: 66%-72%) for PFP, and 96% (95% CI: 94%-97%) for EP. On day 33 PT, the FEC in the MI and PFP groups returned to almost the same values as on day 0, while in the EP group, the FEC remained low. Since MI and PFP proved ineffective, 32 animals were randomly divided into two groups in the second phase. They were treated either with a combination of MI/PFP or EP. The FECR at day 13 PT for the combination MI/PFP was 89% (95% CI: 87%-91%) and 99% (95% CI: 98%-99%) for EP. These results suggest that this A. caninum population is resistant to multiple anthelmintics. Although the combination of MI/PFP improved the anthelmintic efficacy, the FECR remained below 90%. Future studies are indicated to evaluate further the epidemiology of persistent hookworm infections in dogs in the US and to identify more effective treatment protocols as they pose a significant health risk to canine and human health.

Dietary magnesium intakes among women of reproductive age in Ghana-A comparison of two dietary analysis programs.

BACKGROUND: Despite the importance of magnesium to health and most importantly to women of reproductive age who are entering pregnancy, very few surveys have investigated the magnesium status of women of reproductive age, particularly in Africa. Additionally, the software and programs used to analyze dietary intake vary across countries in the region. OBJECTIVE: To assess the dietary magnesium intake of women of reproductive age in Ghana and to compare the estimate of magnesium intake obtained from two commonly used dietary analysis programs. METHODS: We collected magnesium intake from 63 Ghanaian women using a semiquantitative 150-item food frequency questionnaire. Dietary data was analyzed using two different dietary analysis programs, Nutrient Data Software for Research (NDSR) and the Elizabeth Stewart Hands and Associates (ESHA) Food Processor Nutrition Analysis software. We used the Wilcoxon signed rank test to compare the mean differences between the two dietary programs. RESULTS: There were significant differences between the average dietary magnesium intake calculated by the two dietary programs, with ESHA estimating higher magnesium intake than NDSR (M±SE; ESHA: 200 ± 12 mg/day; NDSR: 168 ± 11 mg/day; p<0. 05). The ESHA database included some ethnic foods and was flexible in terms of searching for food items which we found to be more accurate in assessing the magnesium intake of women in Ghana. Using the ESHA software, 84% of the study women had intake below the recommended dietary allowances (RDA) of 320mg/day. CONCLUSION: It is possible that the ESHA software provided an accurate estimate of magnesium in this population because it included specific ethnic foods. Concerted efforts such as magnesium supplementation and nutrition education should be considered to improve the magnesium intake of women of reproductive age in Ghana.

Measurement Invariance and Application of an Alcohol-Related Consequence Scale for American Indian Adolescents.

American Indian (AI) adolescents experience disproportionate alcohol-related consequences. The present study evaluated the psychometric properties and application of the American Drug and Alcohol Survey (ADAS™) alcohol-related consequence scale for AI adolescents through a secondary analysis of a large population-based sample of adolescents living on or near AI reservations. We found support for the ADAS alcohol-related consequence scale as a one-factor model, invariant discretely across race, sex assigned at birth, and age, and with good internal consistency. Evidence for construct validity was found through significant positive correlations between frequency of past 12 months of drinking, frequency of past 12 months of intoxication, and lifetime alcohol-related consequences. AI adolescents were significantly more likely to report more alcohol-related consequences than their non-Hispanic White peers. Race significantly interacted with frequency of drinking in predicting alcohol-related consequences such that these associations were stronger for AI adolescents. However, race did not significantly interact with frequency of intoxication in predicting alcohol-related consequences. Results from this study demonstrate the utility of the ADAS alcohol-related consequence scale for use across demographic groups with little risk of measurement bias.

Trends in Veno-Arterial Extracorporeal Life Support With and Without an Impella or Intra-Aortic Balloon Pump for Cardiogenic Shock.

Background Mechanical circulatory support devices, such as the intra-aortic balloon pump (IABP) and Impella, are often used in patients on veno-arterial extracorporeal life support (VA-ECLS) with cardiogenic shock despite limited supporting clinical trial data. Methods and Results Hospitalizations for cardiogenic shock from 2016 to 2018 were identified from the National Inpatient Sample. Trends in the use of VA-ECLS with and without an IABP or Impella were assessed semiannually. Multivariable logistic regression and general linear regression evaluated the association of Impella and IABP use with in-hospital outcomes. Overall, 12 035 hospitalizations with cardiogenic shock and VA-ECLS were identified, of which 3115 (26%) also received an IABP and 1880 (16%) an Impella. Use of an Impella with VA-ECLS substantially increased from 10% to 18% over this period (P<0.001), whereas an IABP modestly increased from 25% to 26% (P<0.001). In-hospital mortality decreased 54% to 48% for VA-ECLS only, 61% to 58% for VA-ECLS with an Impella, and 54% to 49% for VA-ECLS with an IABP (P<0.001 each). Most (57%) IABPs or Impellas were placed on the same day as VA-ECLS. After adjustment, there were no differences in in-hospital mortality or length of stay with the addition of an IABP or Impella compared with VA-ECLS alone. Conclusions From 2016 to 2018 in the United States, use of an Impella and IABP with VA-ECLS significantly increased. More than half of Impellas and IABPs were placed on the same day as VA-ECLS, and the use of a second mechanical circulatory support device did not impact in-hospital mortality. Further studies are needed to decipher the optimal timing and patient selection for this growing practice.

Evaluation of race and ethnicity disparities in outcome studies of CYP2C19 genotype-guided antiplatelet therapy.

Dual antiplatelet therapy with a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin remains the standard of care for all patients undergoing percutaneous coronary intervention (PCI). It is well-established that patients carrying CYP2C19 no function alleles have impaired capacity to convert clopidogrel into its active metabolite and thus, are at higher risk of major adverse cardiovascular events (MACE). The metabolism and clinical effectiveness of prasugrel and ticagrelor are not affected by CYP2C19 genotype, and accumulating evidence from multiple randomized and observational studies demonstrates that CYP2C19 genotype-guided antiplatelet therapy following PCI improves clinical outcomes. However, most antiplatelet pharmacogenomic outcome studies to date have lacked racial and ethnic diversity. In this review, we will (1) summarize current guideline recommendations and clinical outcome evidence related to CYP2C19 genotype-guided antiplatelet therapy, (2) evaluate the presence of potential racial and ethnic disparities in the major outcome studies supporting current genotype-guided antiplatelet therapy recommendations, and (3) identify remaining knowledge gaps and future research directions necessary to advance implementation of this precision medicine strategy for dual antiplatelet therapy in diverse, real-world clinical settings.

Characterization of functionally deficient SIM2 variants found in patients with neurological phenotypes.

Single-minded 2 (SIM2) is a neuron-enriched basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH/PAS) transcription factor essential for mammalian survival. SIM2 is located within the Down syndrome critical region (DSCR) of chromosome 21, and manipulation in mouse models suggests Sim2 may play a role in brain development and function. During the screening of a clinical exome sequencing database, nine SIM2 non-synonymous mutations were found which were subsequently investigated for impaired function using cell-based reporter gene assays. Many of these human variants attenuated abilities to activate transcription and were further characterized to determine the mechanisms underpinning their deficiencies. These included impaired partner protein dimerization, reduced DNA binding, and reduced expression and nuclear localization. This study highlighted several SIM2 variants found in patients with disabilities and validated a candidate set as potentially contributing to pathology.

Impact of the ABCD-GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi-Site, Real-World Investigation.

The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD-GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD-GENE score to predict the risk for atherothrombotic events in a diverse, real-world population of clopidogrel-treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD-GENE score ≥ 10 vs. < 10. The risk of major atherothrombotic events was higher in patients with an ABCD-GENE score ≥ 10 (n = 505) vs. < 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient-years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23-2.25, P < 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. < 10 (16.7 vs. 10.1 events per 100 patient-years, adjusted HR 1.59, 95% CI 1.11-2.30, P = 0.013). Our diverse, real-world data demonstrate diminished clopidogrel effectiveness in post-PCI patients with an ABCD-GENE score ≥ 10.

Race- and Gender-Based Differences in Cardiac Structure and Function and Risk of Heart Failure.

BACKGROUND: Although heart failure (HF) risk and cardiac structure/function reportedly differ according to race and gender, limited data exist in late life when risk of HF is highest. OBJECTIVES: The goal of this study was to evaluate race/gender-based differences in HF risk factors, cardiac structure/function, and incident HF in late life. METHODS: This analysis included 5,149 HF-free participants from ARIC (Atherosclerosis Risk In Communities), a prospective epidemiologic cohort study, who attended visit 5 (2011-2013) and underwent echocardiography. Participants were subsequently followed up for a median 5.5 years for incident HF/death. RESULTS: Patients' mean age was 75 ± 5 years, 59% were women, and 20% were Black. Male gender and Black race were associated with lower mean left ventricular ejection fraction. Black race was also associated with greater left ventricular wall thickness and concentricity, differences that persisted after adjusting for cardiovascular comorbidities. After adjusting for cardiovascular comorbidities, men were at higher risk for HF and heart failure with reduced ejection fraction (HFrEF) in Black participants compared with White participants (HF: HR of 2.36 [95% CI: 1.37-4.08] vs 1.16 [95% CI: 0.89-1.51], interaction P = 0.016; HFrEF: HR of 3.70 [95% CI: 1.72-7.95] vs 1.55 [95% CI: 1.01-2.37] respectively, interaction P = 0.039). Black race was associated with a higher incidence of HF overall and HFrEF in men only (HF: 1.65 [95% CI: 1.07-2.53] vs 0.76 [95% CI: 0.49-1.17]; HFrEF: HR of 2.55 [95% CI: 1.46-4.44] vs 0.91 [95% CI: 0.46-1.83]). No race/gender-based differences were observed in risk of incident heart failure with preserved ejection fraction. CONCLUSIONS: Among older persons free of HF, men and Black participants exhibit worse systolic performance and are at heightened risk for HFrEF, whereas the risk of heart failure with preserved ejection fraction is similar across gender and race groups.

Posttraumatic Stress Disorder and Substance Misuse Among Black Emerging Adults: The Influence of Social Support.

Objective: Black emerging adults are significantly impacted by substance misuse. Posttraumatic stress disorder (PTSD) is associated with heightened substance misuse among Black emerging adults. However, limited research has identified protective factors that may influence the strength of the relation between PTSD and substance misuse in this population. Addressing this important limitation, the present study examined the potential moderating role of perceived social support in the association between PTSD symptoms and substance (i.e., alcohol and drug) misuse. Methods: Participants were 182 trauma-exposed Black emerging adults (M age = 20.50; 71.3% women) who completed self-report measures assessing PTSD symptoms, alcohol and drug misuse, and perceived social support. Results: PTSD symptoms were significantly and positively correlated with both alcohol and drug misuse. Moderation analyses indicated that positive relations between PTSD symptoms and both alcohol and drug misuse were only significant among Black emerging adults with lower (but not higher) levels of perceived social support. Conclusions: These findings suggest the potential utility of addressing social support in the assessment and treatment of substance misuse in trauma-exposed Black emerging adults.

Association between Dietary Magnesium Intake and Glycemic Markers in Ghanaian Women of Reproductive Age: A Pilot Cross-Sectional Study.

Low magnesium intake has been shown to be associated with an increased risk of type 2 diabetes mellitus (T2DM) in several studies conducted in high-income countries. However, very few studies have been performed in Africa, where many countries have a growing rate of T2DM. We conducted a pilot cross-sectional study among 63 women in Ghana to investigate the association between magnesium intake and glycemic markers. We assessed dietary magnesium using a food frequency questionnaire and glycemic markers using fasting blood glucose and glycated hemoglobin A1c (HbA1c). Our findings showed that the mean magnesium intake was 200 ± 116 mg/day. The prevalence of T2DM was 5% by measuring fasting blood glucose and 8% by measuring HbA1c. Unadjusted linear regression models revealed that higher magnesium intake significantly predicted higher fasting blood glucose levels (ß = 0.31; 95% CI: 0.07, 0.55; p = 0.01) and HbA1c levels (ß = 0.26; 95% CI: 0.01, 0.51; p = 0.04). In adjusted analyses, magnesium intake was no longer significantly associated with either fasting blood glucose levels (ß = 0.22; 95% CI: -0.03, 0.46; p = 0.08) or HbA1c levels (ß = 0.15; 95% CI: -0.08, 0.39; p = 0.20). In conclusion, our study did not show a significant association between magnesium intake and glycemic markers in women of reproductive age in Ghana. The results of this study need to be further substantiated because this was the first study to examine magnesium intake and glycemic markers in this population in Africa.

Effect of the STAMP (Sharing and Talking About My Preferences) Intervention on Completing Multiple Advance Care Planning Activities in Ambulatory Care : A Cluster Randomized Controlled Trial.

BACKGROUND: Interventions with the potential for broad reach in ambulatory settings are necessary to achieve a life course approach to advance care planning. OBJECTIVE: To examine the effect of a computer-tailored, behavioral health model-based intervention on the engagement of adults in advance care planning recruited from ambulatory care settings. DESIGN: Cluster randomized controlled trial with participant-level analysis. (ClinicalTrials.gov: NCT03137459). SETTING: 10 pairs of primary and selected specialty care practices matched on patient sociodemographic information. PARTICIPANTS: English-speaking adults aged 55 years or older; 454 adults at practices randomly assigned to usual care and 455 at practices randomly assigned to intervention. INTERVENTION: Brief telephone or web-based assessment generating a mailed, individually tailored feedback report with a stage-matched brochure at baseline, 2 months, and 4 months. MEASUREMENTS: The primary outcome was completion of the following 4 advance care planning activities at 6 months: identifying and communicating with a trusted person about views on quality versus quantity of life, assignment of a health care agent, completion of a living will, and ensuring that the documents are in the medical record-assessed by a blinded interviewer. Secondary outcomes were completion of individual advance care planning activities. RESULTS: Participants were 64% women and 76% White. The mean age was 68.3 years (SD, 8.3). The predicted probability of completing all advance care planning activities in usual care sites was 8.2% (95% CI, 4.9% to 11.4%) versus 14.1% (CI, 11.0% to 17.2%) in intervention sites (adjusted risk difference, 5.2 percentage points [CI, 1.6 to 8.8 percentage points]). Prespecified subgroup analysis found no statistically significant interactions between the intervention and age, education, or race. LIMITATIONS: The study was done in a single region and excluded non-English speaking participants. No information was collected about nonparticipants. CONCLUSION: A brief, easily delivered, tailored print intervention increased participation in advance care planning in ambulatory care settings. PRIMARY FUNDING SOURCE: National Institute of Nursing Research and National Institute of Aging.