Developing an agent-based model of oral healthcare utilization by Chinese Americans in New York City.

Many Chinese Americans experience certain barriers (e.g., low income, English as a second language, lack of insurance, cultural differences, discrimination) when they seek oral healthcare services. These barriers may contribute to health disparities by discouraging use (leading to reduced utilization) of preventive and treatment services. This research adopts a modeling approach to develop theory that accounts for dynamic relationships operating at multiple levels, from individuals to families to communities. A multi-method and multi-level modeling approach allows for the interaction of factors at different levels of aggregation. This research applies spatially explicit agent-based modeling to examine how demographic, socioeconomic, and geographic factors shape access to oral healthcare for low-income Chinese Americans in New York City. The simulation model developed in this research was used to test different intervention scenarios involving community health workers who facilitate care coordination and other health promotion activities. In addition to demographic characteristics and socioeconomic factors, this study also considers geographic factors and spatial behavior, such as distance and activity space. The overarching contribution of this study is to provide a complex systems science framework to better understand access to oral healthcare for urban Chinese Americans, toward adapting it for other racial/ethnic minority groups, by integrating health-seeking behaviors at the individual level, barriers to care at multiple levels, and opportunities for health promotion at the community level.

Validation of the factors influencing family consent for organ donation in the UK.

Between 2013 and 2019, there was an increase in the consent rate for organ donation in the UK from 61% to 67%, but this remains lower than many European countries. Data on all family approaches (16,896) for donation in UK intensive care units or emergency departments between April 2014 and March 2019 were extracted from the referral records and the national potential donor audit held by NHS Blood and Transplant. Complete data were available for 15,465 approaches. Consent for donation after brain death was significantly higher than for donation after circulatory death, 70% (4260/6060) vs. 60% (5645/9405), (OR 1.58, 95%CI 1.47-1.69). Patient ethnicity, religious beliefs, sex and socio-economic status, and knowledge of a patient's donation decision were strongly associated with consent (p < 0.001). These factors should be addressed by medium- to long-term strategies to increase community interventions, encouraging family discussions regarding donation decisions and increasing registration on the organ donor register. The most readily modifiable factor was the involvement of an organ donation specialist nurse at all stages leading up to the approach and the approach itself. If no organ donation specialist nurse was present, the consent rates were significantly lower for donation after brain death (OR 0.31, 95%CI 0.23-0.42) and donation after cardiac death (OR 0.26, 95%CI 0.22-0.31) compared with if a collaborative approach was employed. Other modifiable factors that significantly improved consent rates included less than six relatives present during the formal approach; the time from intensive care unit admission to the approach (less for donation after brain death, more for donation after cardiac death); family not witnessing neurological death tests; and the relationship of the primary consenter to the patient. These modifiable factors should be taken into consideration when planning the best bespoke approach to an individual family to discuss the option of organ donation as an end-of-life care choice for the patient.

Cost-Effectiveness of Alirocumab in Patients With Acute Coronary Syndromes: The ODYSSEY OUTCOMES Trial.

BACKGROUND: Cholesterol reduction with proprotein convertase subtilisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute coronary syndrome remains uncertain. OBJECTIVES: This study sought to determine whether further cholesterol reduction with alirocumab would be cost-effective in patients with a recent acute coronary syndrome on optimal statin therapy. METHODS: A cost-effectiveness model leveraging patient-level data from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was developed to estimate costs and outcomes over a lifetime horizon. Patients (n = 18,924) had a recent acute coronary syndrome and were on high-intensity or maximum-tolerated statin therapy, with a baseline low-density lipoprotein cholesterol (LDL-C) level ≥70 mg/dl, non-high-density lipoprotein cholesterol ≥100 mg/dl, or apolipoprotein B ≥80 mg/l. Alirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Alirocumab was blindly titrated to 150 mg if LDL-C remained ≥50 mg/dl or switched to placebo if 2 consecutive LDL-C levels were <15 mg/dl. Incremental cost per quality-adjusted life-year (QALY) was determined with the addition of alirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels ≥100 mg/dl and <100 mg/dl. RESULTS: Across the overall population recruited to the ODYSSEY OUTCOMES trial, using an annual treatment cost of US$5,850, the mean overall incremental cost-effectiveness ratio was US$92,200 per QALY (base case). The cost was US$41,800 per QALY in patients with baseline LDL-C ≥100 mg/dl, whereas in those with LDL-C <100 mg/dl the cost per QALY was US$299,400. Among patients with LDL-C ≥100 mg/dl, incremental cost-effectiveness ratios remained below US$100,000 per QALY across a wide variety of sensitivity analyses. CONCLUSIONS: In patients with a recent acute coronary syndrome on optimal statin therapy, alirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C ≥100 mg/dl but less economic value with LDL-C <100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402).

Cost implications of intraprocedural thrombotic events and bleeding in percutaneous coronary intervention: Results from the CHAMPION PHOENIX ECONOMICS Study.

BACKGROUND: Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. METHODS: PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. RESULTS: IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). CONCLUSIONS: IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI.

Incidence, Predictors, and Outcomes of Acquired Thrombocytopenia After Percutaneous Coronary Intervention: A Pooled, Patient-Level Analysis of the CHAMPION Trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition).

BACKGROUND: The influence of cangrelor on the incidence and outcomes of post-percutaneous coronary intervention (PCI) thrombocytopenia is not defined. We aimed to explore the incidence, predictors, and clinical impact of thrombocytopenia after PCI in cangrelor-treated patients. METHODS AND RESULTS: This was a pooled, patient-level analysis of the CHAMPION trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition), which compared cangrelor with clopidogrel for prevention of thrombotic complications during and after PCI. Acquired thrombocytopenia was defined as either a drop in platelet count to <100 000 after PCI or a drop of >50% between baseline and a follow-up. The main efficacy outcome was major adverse cardiac events. The primary safety outcome was noncoronary artery bypass grafting-related Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries-defined severe bleeding at 48 hours. Patients (23 783) were enrolled, and 3009 (12.7%) received a GPI (glycoprotein IIb/IIIa inhibitor). Acquired thrombocytopenia occurred in 200 patients (0.8%). The adjusted rate of major adverse cardiovascular events at 48 hours was significantly higher in patients who developed thrombocytopenia compared with those who did not (odds ratio, 3.00; 95% confidence interval, 1.89-4.69; P<0.001), as was major bleeding (odds ratio, 14.71; 95% confidence interval, 5.96-36.30; P<0.001). GPI use was the strongest independent predictor of acquired thrombocytopenia (odds ratio, 2.93; 95% confidence interval, 2.15-3.97; P<0.0001). There was no difference in the rate of acquired thrombocytopenia in patients randomized to cangrelor or clopidogrel. CONCLUSIONS: Acquired thrombocytopenia after PCI is strongly associated with substantial early morbidity and mortality, as well as major bleeding. GPI use is a significant predictor of thrombocytopenia. Cangrelor is not associated with acquired thrombocytopenia, and its clinical efficacy and safety is consistent irrespective of thrombocytopenia occurrence. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00305162, NCT00385138, and NCT01156571.

Estimating peer density effects on oral health for community-based older adults.

BACKGROUND: As part of a long-standing line of research regarding how peer density affects health, researchers have sought to understand the multifaceted ways that the density of contemporaries living and interacting in proximity to one another influence social networks and knowledge diffusion, and subsequently health and well-being. This study examined peer density effects on oral health for racial/ethnic minority older adults living in northern Manhattan and the Bronx, New York, NY. METHODS: Peer age-group density was estimated by smoothing US Census data with 4 kernel bandwidths ranging from 0.25 to 1.50 mile. Logistic regression models were developed using these spatial measures and data from the ElderSmile oral and general health screening program that serves predominantly racial/ethnic minority older adults at community centers in northern Manhattan and the Bronx. The oral health outcomes modeled as dependent variables were ordinal dentition status and binary self-rated oral health. After construction of kernel density surfaces and multiple imputation of missing data, logistic regression analyses were performed to estimate the effects of peer density and other sociodemographic characteristics on the oral health outcomes of dentition status and self-rated oral health. RESULTS: Overall, higher peer density was associated with better oral health for older adults when estimated using smaller bandwidths (0.25 and 0.50 mile). That is, statistically significant relationships (p < 0.01) between peer density and improved dentition status were found when peer density was measured assuming a more local social network. As with dentition status, a positive significant association was found between peer density and fair or better self-rated oral health when peer density was measured assuming a more local social network. CONCLUSIONS: This study provides novel evidence that the oral health of community-based older adults is affected by peer density in an urban environment. To the extent that peer density signifies the potential for social interaction and support, the positive significant effects of peer density on improved oral health point to the importance of place in promoting social interaction as a component of healthy aging. Proximity to peers and their knowledge of local resources may facilitate utilization of community-based oral health care.

The CanPain SCI Clinical Practice Guideline for Rehabilitation Management of Neuropathic Pain after Spinal Cord: recommendations for model systems of care.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The project objectives were to develop the first Canadian recommendations on a model of care for the management of at- and below-level neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: On the basis of a review of the Accreditation Canada standards, the Steering Committee developed questions to guide the CanPainSCI Working Group when developing the recommendations. The Working Group agreed on recommendations through a consensus process. RESULTS: The Working Group developed five recommendations for the organization of neuropathic pain rehabilitation care in people with SCI. CONCLUSIONS: The Working Group recommendations for a model of care for at- and below-level neuropathic pain after SCI should be used to inform clinical practice.

Lack of Concordance Between Local Investigators, Angiographic Core Laboratory, and Clinical Event Committee in the Assessment of Stent Thrombosis: Results From the TRACER Angiographic Substudy.

BACKGROUND: Stent thrombosis (ST) is an important end point in cardiovascular clinical trials. Adjudication is traditionally based on clinical event committee (CEC) review of case report forms and source documentation rather than angiograms. However, the degree to which this method of adjudication is concordant with the review of independent angiographic core laboratories (ACLs) has not been studied. This report represents the first assessment of variability between local investigators (LIs), a CEC, and an ACL. METHODS AND RESULTS: Serial angiograms of 329 patients with acute coronary syndrome without ST-segment-elevation who underwent percutaneous coronary intervention at entry in the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Particpants With Acute Coronary Syndrome (TRACER) and who met criteria for possible ST subsequent to the index event were reviewed by an ACL. The ACL was blinded to the assessment by both LIs and the CEC regarding the presence or absence of ST. CEC adjudication was based on Academic Research Consortium definitions of ST, using case report form data and source documents, including catheterization laboratory reports. The ACL, CEC, and LIs agreed on the presence or absence of ST in 52.9% events (κ=0.32; 95% confidence interval, 0.26-0.39). The ACL and CEC agreed on 82.7% of events (κ=0.57; 95% confidence interval, 0.47-0.67); the ACL and LIs agreed on 61.1% of events (κ=0.25; 95% confidence interval, 0.16-0.34); and the CEC and LIs agreed on 62% of events (κ=0.28; 95% confidence interval, 0.21-0.36). CONCLUSIONS: ST reporting by an ACL, a CEC, and LIs is discordant. The assessment of ST is more often detected by direct review of angiograms by an ACL. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00527943.

Causes and costs for ED visits after pediatric adenotonsillectomy.

OBJECTIVE: (1) Review the reasons, timing, and costs for children presenting to the emergency department (ED) after adenotonsillectomy (T&A). STUDY DESIGN: Case series with chart review. SETTING: Tertiary care children's hospital. SUBJECTS AND METHODS: A standardized activity-based hospital accounting system was used to identify 437 children from an academic pediatric otolaryngology practice presenting to the ED after T&A from 2009 to 2012. The reason for presentation, timing after surgery, and facility costs were recorded. RESULTS: The study cohort represented 13.3% of the 3198 patients who underwent T&A during that time period. Overall, 133 (4.2%) presented for dehydration, 106 (3.3%) presented for post-tonsillectomy hemorrhage, 65 (2.0%) for poorly controlled pain, 42 (1.3%) for fever, 29 (1.0%) for vomiting/nausea/GI discomfort, 22 (0.7%) for respiratory complications, and 12 (0.4%) for miscellaneous reasons related to the operation; 28 (0.8%) were unrelated to the T&A and excluded. Mean postoperative day at the time of ED presentation was 4.4 (95% CI, 4.1-4.7). The mean cost per patient presenting to the ED was $1420 (95% CI, $1104-$1737), the most costly subgroups being those presenting with respiratory complications ($2855; 95% CI, $1434-$4277), hemorrhage ($1502; 95% CI, $1216-$1787), and dehydration ($1372; 95% CI, $995-$1750). The least costly subgroup was acute postoperative pain ($781; 95% CI, $282-$1200). CONCLUSION: A significant portion of children present to the ED after T&A for poorly controlled pain, dehydration, or fever. The costs from these visits are significant. Accounting for these costs in the global care for pediatric T&A could assist in calculating appropriate reimbursement for bundled payments in this climate of health care reform.

Impact of Human Development Index on the profile and outcomes of patients with acute coronary syndrome.

OBJECTIVE: To study the impact of national economic and human development status on patient profiles and outcomes in the setting of acute coronary syndrome (ACS). METHODS: We conducted a retrospective analysis of the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial (TRILOGY ACS) population (51 countries; 9301 patients). Outcome measures compared baseline characteristics and clinical outcomes through 30 months by 2010 country-level United Nations Human Development Indices (HDIs) and per-capita gross national income. RESULTS: TRILOGY ACS enrolled 3659 patients from 27 very-high HDI countries, 3744 from 18 high-HDI countries and 1898 from 6 medium-HDI countries. Baseline characteristics of groups varied significantly, with the medium-HDI group having a lower mean age (63.0 years, vs 65.0 and 68.0 years for high-HDI and very-high HDI, respectively; p<0.001), lower baseline Global Registry of Acute Coronary Events risk score and lower rate of non-ST-segment elevation myocardial infarction (58.0%, vs 62.2% and 83.9% among high-HDI and very-high HDI, respectively). Medium-HDI and high-HDI patients had lower unadjusted 30-month rates for the composite of cardiovascular death/myocardial infarction/stroke (17.6%, 16.9% and 23.1% for medium-HDI, high-HDI and very-high HDI, respectively); this difference disappeared after adjusting for baseline characteristics. Adjusted HRs for the composite endpoint were lower in lower-income/middle-income countries vs upper-income/middle-income (0.791(95% CI 0.632 to 0.990)) and high-income countries (0.756 (95% CI 0.616 to 0.928)), with differences largely attributable to myocardial infarction rates. CONCLUSIONS: Clinical patient profiles differed substantially by country HDI groupings. Lower unadjusted event rates in medium-HDI countries may be explained by younger age and lower comorbidity burden among these countries' patients. This heterogeneity in patient recruitment across country HDI groupings may have important implications for future global ACS trial design. TRIAL REGISTRATION NUMBER: NCT00699998.

Cardiovascular risk assessment of South Asians in a religious setting: a feasibility study.

AIMS: South Asians in the UK have high cardiovascular disease (CVD) mortality. Therefore, this population is likely to benefit from screening programmes. To address this issue, an initiative was set up between the Royal Free Hampstead NHS Trust, H.E.A.R.T. UK and two Hindu temples in North London to provide screening for CVD risk factors in the community. METHODS: A total of 434 individuals of Gujarati Indian origin were screened. Measurements included anthropometry, blood pressure and lipid profiles. Three different scoring systems: Framingham, Joint British Societies' 2 and QRISK2 were used to estimate CVD risk. RESULTS: At least one modifiable CVD risk factor was present in 92% of the individuals screened; 52% were hypertensive, 40% were obese, 75% had central adiposity and 10% had total cholesterol/high density lipoprotein cholesterol ratio > 6. In addition, 37% of a subset of 104 individuals with a fasting sample fulfilled the diagnostic criteria for metabolic syndrome. Overall, 15% of participants screened had a 10-year CV risk score > 20% using QRISK2. The three risk score calculators showed moderate agreement: QRISK2 and JBS2 (kappa 0.61, 95% CI 0.54-0.67), QRISK2 and Framingham (kappa 0.63, 95% CI 0.57-0.70) and JBS2 and Framingham (kappa 0.70, 95% CI 0.64-0.75). CONCLUSIONS: A high prevalence of modifiable risk factors for CVD was detected in the population screened.

Incidence and clinical consequences of acquired thrombocytopenia after antithrombotic therapies in patients with acute coronary syndromes: results from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.

BACKGROUND: The aim of the study was to investigate the incidence and clinical consequences of acquired thrombocytopenia in patients with acute coronary syndromes (ACS) in the ACUITY trial. METHODS: We examined 10,836 patients with ACS randomized to receive heparin plus glycoprotein (GP) IIb/IIIa inhibitor, bivalirudin plus GP IIb/IIIa inhibitor, or bivalirudin monotherapy. RESULTS: Acquired thrombocytopenia developed in 740 (6.8%) patients; mild (100,000-150,000 platelets/mm³), moderate (50,000-100,000 platelets/mm³), and severe (< 50,000 platelets/mm³) developed in 656 (6%), 51 (0.5%), and 33 (0.3%) patients, respectively. Patients with acquired thrombocytopenia, compared with those without, were more likely to develop major bleeding (14% vs 4.3%, P < .0001) at 30 days and had higher rates of mortality (6.5% vs 3.4%, P < .0001) at 1 year. By multivariate analysis, acquired thrombocytopenia was an independent predictor of major bleeding at 30 days (hazard ratio [HR] 1.68, 95% CI 1.04-2.72, P = .03). Moderate and severe acquired thrombocytopenia were predictors of mortality at 1 year (HR 2.89, 95% CI 0.92-9.06, P = .06, and HR 3.41, 95% CI 1.09-10.68, P = .03, respectively). Compared to heparin plus GP IIb/IIIa inhibitor, bivalirudin monotherapy was associated with less declines in platelet count by >25% (7.6% vs 5.6%, P = .0009) and >50% (1.4% vs 0.7%, P = .004) from baseline. CONCLUSIONS: Acquired thrombocytopenia occurs in approximately 1 in 14 patients with ACS treated with antithrombin and antiplatelet medications and is strongly associated with hemorrhagic and ischemic complications. Compared to an anticoagulant regimen including a GP IIb/IIIa inhibitor, administration of bivalirudin monotherapy appears to be associated with less frequent declines in platelet count.

A severity scoring system for risk assessment of patients with cardiogenic shock: a report from the SHOCK Trial and Registry.

BACKGROUND: Early revascularization (ERV) is beneficial in the management of cardiogenic shock (CS) complicating myocardial infarction. The severity of CS varies widely, and identification of independent risk factors for outcome is needed. The effect of ERV on mortality in different risk strata is also unknown. We created a severity scoring system for CS and used it to examine the potential benefit of ERV in different risk strata using data from the SHOCK Trial and Registry. METHODS: Data from 1,217 patients (294 from the randomized trial and 923 from the registry) with CS due to pump failure were included in a Stage 1 severity scoring system using clinical variables. A Stage 2 scoring system was developed using data from 872 patients who had invasive hemodynamic measurements. The outcome was in-hospital mortality at 30 days. RESULTS: In-hospital mortality at 30 days was 57%. Multivariable modeling identified 8 risk factors (Stage 1): age, shock on admission, clinical evidence of end-organ hypoperfusion, anoxic brain damage, systolic blood pressure, prior coronary artery bypass grafting, noninferior myocardial infarction, and creatinine > or = 1.9 mg/dL (c-statistic = 0.74). Mortality ranged from 22% to 88% by score category. The ERV benefit was greatest in moderate- to high-risk patients (P = .02). The Stage 2 model based on patients with pulmonary artery catheterization included age, end-organ hypoperfusion, anoxic brain damage, stroke work, and left ventricular ejection fraction <28% (c-statistic = 0.76). In this cohort, the effect of ERV did not vary by risk stratum. CONCLUSIONS: Simple clinical predictors provide good discrimination of mortality risk in CS complicating myocardial infarction. Early revascularization is associated with improved survival across a broad range of risk strata.

A model for predicting mortality in acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: results from the Assessment of Pexelizumab in Acute Myocardial Infarction Trial.

BACKGROUND: Accurate models to predict mortality are needed for risk stratification in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: We examined 5745 patients with STEMI undergoing primary PCI in the Assessment of Pexelizumab in Acute Myocardial Infarction Trial within 6 hours of symptom onset. A Cox proportional hazards model incorporating regression splines to accommodate nonlinearity in the log hazard ratio (HR) scale was used to determine baseline independent predictors of 90-day mortality. At 90 days, 271 (4.7%) of 5745 patients died. Independent correlates of 90-day mortality were (in descending order of statistical significance) age (HR, 2.03/10-y increments; 95% CI, 1.80 to 2.29), systolic blood pressure (HR, 0.86/10-mm Hg increments; 95% CI, 0.82 to 0.90), Killip class (class 3 or 4 versus 1 or 2) (HR, 4.24; 95% CI, 2.97 to 6.08), heart rate (>70 beats per minute) (HR, 1.45/10-beat increments; 95% CI, 1.31 to 1.59), creatinine (HR, 1.23/10-µmol/L increments >90 µmol/L; 95% CI, 1.13 to 1.34), sum of ST-segment deviations (HR, 1.25/10-mm increments; 95% CI, 1.11 to 1.40), and anterior STEMI location (HR, 1.47; 95% CI, 1.12 to 1.93) (c-index, 0.82). Internal validation with bootstrapping confirmed minimal overoptimism (c-index, 0.81). CONCLUSIONS: Our study provides a practical method to assess intermediate-term prognosis of patients with STEMI undergoing primary PCI, using baseline clinical and ECG variables. This model identifies key factors affecting prognosis and enables quantitative risk stratification that may be helpful in guiding clinical care and for risk adjustment for observational analyses.

Prognostic modeling of individual patient risk and mortality impact of ischemic and hemorrhagic complications: assessment from the Acute Catheterization and Urgent Intervention Triage Strategy trial.

BACKGROUND: Both ischemic and hemorrhagic complications increase mortality rate in acute coronary syndromes. Their frequency and relative importance vary according to individual patient risk profiles. We sought to develop prognostic models for the risk of myocardial infarction (MI) and major bleeding to assess their impact on risk of death and to examine the manner in which alternative antithrombotic regimens affect these risks in individual patients. METHODS AND RESULTS: The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial randomized 13 819 patients with acute coronary syndrome to heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. By logistic regression, there were 5 independent predictors of MI within 30 days (n=705; 5.1%) and 8 independent predictors of major bleeding (n=645; 4.7%), only 2 of which were common to both event types. In a covariate-adjusted, time-updated Cox regression model, both MI and major bleeding significantly affected subsequent mortality rate (hazard ratios, 2.7 and 2.9, respectively; both P<0.001). Treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor was associated with a nonsignificant 8% increase in MI and a highly significant 50% decrease in major bleeding. Given the individual patient risk profiles and the fact that bivalirudin prevented approximately 6 major bleeds for each MI that might occur from its use, the estimated reduction in bleeding was greater than the estimated increase in MI by bivalirudin alone rather than heparin plus a glycoprotein IIb/IIIa inhibitor for nearly all patients. CONCLUSIONS: Consideration of the individual patient risk profile for MI and major bleeding and the relative treatment effects of alternative pharmacotherapies permits personalized decision making to optimize therapy of patients with acute coronary syndrome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00093158.

Gastrointestinal bleeding in patients with acute coronary syndromes: incidence, predictors, and clinical implications: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial.

OBJECTIVES: We assessed the incidence, predictors, and outcomes of gastrointestinal bleeding (GIB) in patients with acute coronary syndromes (ACS). BACKGROUND: GIB is a potential hemorrhagic complication in patients with ACS treated with antithrombotic and/or antiplatelet medications. The clinical outcomes associated with GIB in this setting have not been systematically studied. METHODS: In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients with moderate- and high-risk ACS, enrolled at 450 centers in 17 countries between August 2003 and December 2005, were randomized to the open-label use of 1 of 3 antithrombin regimens (heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin monotherapy). RESULTS: GIB within 30 days occurred in 178 patients (1.3%). Older age, baseline anemia, longer duration of study drug administration before angiogram, smoking, ST-segment deviation>or=1 mm, and diabetes were identified as independent predictors of GIB. On multivariable analysis, GIB was strongly associated with 30-day all-cause mortality (hazard ratio [HR]: 4.87 [interquartile range (IQR) 2.61 to 9.08], p<0.0001), cardiac mortality (HR: 5.35 [IQR 2.71 to 10.59], p<0.0001), and composite ischemia (HR: 1.94 [IQR 1.14 to 3.30], p=0.014), as well as with 1-year all-cause mortality (HR: 3.97 [IQR 2.64 to 5.99], p<0.0001), cardiac mortality (HR: 3.77 [IQR 2.14 to 6.63], p<0.0001), myocardial infarction (HR: 1.74 [IQR 1.01 to 3.02], p=0.047), and composite ischemia (HR: 1.90 [IQR 1.37 to 2.64], p=0.0001). Patients who experienced GIB had significantly higher rates of stent thrombosis compared with patients without GIB (5.8% vs. 2.4%, p=0.009). CONCLUSIONS: GIB is a serious condition in the scenario of ACS and is independently associated with mortality and ischemic complications.

Pharmacological and clinical profile of bivalirudin in the treatment of patients with acute coronary syndrome.

BACKGROUND: Bivalirudin is a direct thrombin inhibitor with several pharmacological advantages over heparin. It has been studied extensively in non-ST elevation acute 60 coronary syndromes (NSTE-ACS) and in percutaneous coronary intervention. Bivalirudin has also recently been investigated in patients with ST-elevation myocardial infarction (STEMI) treated with primary angioplasty and stenting. More than 27,000 patients were randomized in these trials. OBJECTIVE: To provide an overview of the pharmacological properties of bivalirudin and its efficacy and safety profile in patients across the spectrum of acute coronary syndromes (ACS). METHODS: All published, peer-reviewed clinical trials were reviewed and as relevant were included. RESULTS AND CONCLUSIONS: Bivalirudin with provisional IIb/IIIa antagonists provides consistent results across the full spectrum of ACS, with similar or non-inferior protection from ischemic events and significantly reduces bleeding complications compared with heparin and IIb/IIIa antagonists. In STEMI, mortality at 30 days and 1 year is significantly reduced. The unique pharmacokinetic profile of bivalirudin allows for simultaneous reductions in both ischemic and hemorrhagic events and makes it an appropriate alternative to heparin.

Determining the in-hospital cost of bleeding in patients undergoing percutaneous coronary intervention.

BACKGROUND: The economic impact of bleeding in the setting of nonemergent percutaneous coronary intervention (PCI) is poorly understood and complicated by the variety of bleeding definitions currently employed. This retrospective analysis examines and contrasts the in-hospital cost of bleeding associated with this procedure using six bleeding definitions employed in recent clinical trials. METHODS: All nonemergent PCI cases at Christiana Care Health System not requiring a subsequent coronary artery bypass were identified between January 2003 and March 2006. Bleeding events were identified by chart review, registry, laboratory, and administrative data. A microcosting strategy was applied utilizing hospital charges converted to costs using departmental level direct cost-to-charge ratios. The independent contributions of bleeding, both major and minor, to cost were determined by multiple regression. Bootstrap methods were employed to obtain estimates of regression parameters and their standard errors. RESULTS: A total of 6,008 cases were evaluated. By GUSTO definitions there were 65 (1.1%) severe, 52 (0.9%) moderate, and 321 (5.3%) mild bleeding episodes with estimated bleeding costs of $14,006; $6,980; and $4,037, respectively. When applying TIMI definitions there were 91 (1.5%) major and 178 (3.0%) minor bleeding episodes with estimated costs of $8,794 and $4,310, respectively. In general, the four additional trial-specific definitions identified more bleeding events, provided lower estimates of major bleeding cost, and similar estimates of minor bleeding costs. CONCLUSIONS: Bleeding is associated with considerable cost over and above interventional procedures; however, the choice of bleeding definition impacts significantly on both the incidence and economic consequences of these events.