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Background: Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial infarction in patients with either stable coronary artery disease (CAD) or peripheral artery disease (PAD). The cost-effectiveness of this regimen in this population is essential for decision-makers to know. Methods: US direct healthcare system costs (in USD) were applied to hospitalized events, procedures and study drugs utilized by all patients. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 23 months) plus quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) over a lifetime using a two-state Markov model with 1-year cycle length. Sensitivity analyses were performed on the price of rivaroxaban and the annual discontinuation rate. Results: The costs of events and procedures were reduced for Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) patients who received rivaroxaban 2.5 mg orally (BID) plus acetylsalicylic acid (ASA) compared with ASA alone. Total costs were higher for the combination group ($7426 versus $4173) after considering acquisition costs of the study drug. Over a lifetime, patients receiving rivaroxaban plus ASA incurred $27,255 more and gained 1.17 QALYs compared with those receiving ASA alone resulting in an ICER of $23,295/QALY. ICERs for PAD only and polyvascular disease subgroups were lower. Conclusion: Rivaroxaban 2.5 mg BID plus ASA compared with ASA alone was cost-effective (high value) in the USA. COMPASS ClinicalTrials.gov identifier: NCT01776424. [ABSTRACT FROM AUTHOR]

To explore the associations between race and retinoblastoma diagnosis in United States children. In this analytical nonconcurrent cohort study, we used 1988-2018 data from the Surveillance, Epidemiology, and End-Results (SEER) database. Children ages 0-17 with retinoblastoma were included (n = 758); those with missing data were excluded (n = 11; final cohort: n = 747). The exposure variable was race (White, Black, Asian/Pacific Islanders, American Indian/Alaska Native), and the outcome variable was diagnosis of retinoblastoma before versus after 2 years of age. Covariates included sex, rural-urban continuum, ethnicity, decade of diagnosis, and laterality of disease. Unadjusted and adjusted logistic regression analyses were performed to calculate odds ratios and 95% confidence intervals. No statistically significant association was found between racial/ethnic groups (OR = 0.61-0.99; P = 0.92) and age at diagnosis (OR = 0.86; P = 0.66). Females were more likely to be diagnosed earlier than males (OR = 0.62; 95% CI, 0.44-0.88; P = 0.042). No association was found between urban versus rural subjects (OR = 1.02; 95% CI, 0.60-1.75) or between decades (OR = 0.81; 95% CI, 0.54-1.22 and OR 0.96; 95% CI, 0.62-1.47). We found no statistically significant difference between racial/ethnic groups for diagnosis of children with retinoblastoma after 2 years of age. Future studies could explore why females are more likely than males to be diagnosed before 2 years of age. [ABSTRACT FROM AUTHOR]

As America's opioid crisis has become an "epidemic of epidemics," Ohio has been identified as one of the high burden states regarding fentanyl-related overdose mortality. This study aims to examine changes in the availability of fentanyl, fentanyl analogs, and other non-pharmaceutical opioids on cryptomarkets and assess relationship with the trends in unintentional overdoses in Ohio to provide timely information for epidemiologic surveillance. Cryptomarket data were collected at two distinct periods of time: (1) Agora data covered June 2014-September 2015 and were obtained from Grams archive; (2) Dream Market data from March-April 2018 were extracted using a dedicated crawler. A Named Entity Recognition algorithm was developed to identify and categorize the type of fentanyl and other synthetic opioids advertised on cryptomarkets. Time-lagged correlations were used to assess the relationship between the fentanyl, fentanyl analog and other synthetic opioid-related ads from cryptomarkets and overdose data from the Cincinnati Fire Department Emergency Responses and Montgomery County Coroner's Office. Analysis from the cryptomarket data reveals increases in fentanyl-like drugs and changes in the types of fentanyl analogues and other synthetic opioids advertised in 2015 and 2018 with potent substances like carfentanil available during the second period. The time-lagged correlation was the largest when comparing Agora data to Cincinnati Emergency Responses 1 month later 0.84 (95% CI 0.45, 0.96). The time-lagged correlation between Agora data and Montgomery County drug overdoses was the largest when comparing synthetic opioid-related Agora ads to Montgomery County overdose deaths 7 months later 0.78 (95% CI 0.47, 0.92). Further investigations are required to establish the relationship between cryptomarket availability and unintentional overdose trends related to specific fentanyl analogs and/or other illicit synthetic opioids. [ABSTRACT FROM AUTHOR]

Prior studies report lower issue costs for shelf registered debt and conclude that the benefits of increased underwriter competition can be realized by those firms using this registration procedure. This study re-examines the purported superiority of issuing debt via shelf registration, and finds that the savings in issue costs displayed by earlier studies can be attributed to a self selection bias and not the method of registration. [ABSTRACT FROM AUTHOR]

This article analyzes the formation of space oceanography as a scientific specialty, in France and in the United States. Throughout much of its history, oceanography has relied upon a broad range of instrumentation (bathyscaphes, tide gauges, and so forth). The importance of instrumentation meant that many of the exchanges during major scientific meetings in the 1960s focused on engineering problems. As a result, institutional investments by NASA and the French space agency, the Centre National d'Études Spatiales (CNES) supported advances in instrumentation. The emergence of the climate change issue made it possible to merge several factors (technical, geopolitical, and institutional) into the specialty of space oceanography. The birth of a scientific specialty requires the conjunction of several determining factors: a powerful disciplinary basis, a technological innovation resulting in major advances, and scientific politicians capable of tackling new problems. The development of space oceanography provides an excellent example of the origin of a new scientific specialty. The purpose of this article is to trace the history of the combination of the technical and scientific factors that resulted in the origin of space oceanography. This article will focus on specific events that led to the origin of space oceanography, in particular on a series of meetings organized by researchers interested in very specific technical questions. Many of the classical questions of oceanography could be addressed and dealt with by developing and using new instruments (e.g. radar altimeters). To document how the specialty of space oceanography developed, I propose to follow American and French examples of the transformations induced by space oceanography. Such a comparison makes it possible to measure the differential scientific 'maturity' of a nascent speciality. The emergence of climate change research, starting in the 1970s, reorganized many of the oceanographic research questions and legitimized the extension of the discipline into geospatial research. One goal of this article is to understand how this development of science policy influenced interactions between different disciplines. [ABSTRACT FROM AUTHOR]

Objective: Twitter data offer new possibilities for tracking health-related communications. This study is among the first to apply advanced information processing to identify geographic and content features of cannabis-related tweeting in the United States.Method: Tweets were collected using streaming Application Programming Interface (March-May 2016) and were processed by eDrugTrends to identify geolocation and classify content by source (personal communication, media, retail) and sentiment (positive, negative, neutral). States were grouped by cannabis legalization policies into "recreational," "medical, less restrictive," "medical, more restrictive," and "illegal." Permutation tests were performed to analyze differences among four groups in adjusted percentages of all tweets, unique users, personal communications only, and positive-to-negative sentiment ratios.Results: About 30% of all 13,233,837 cannabis-related tweets had identifiable state-level geo-information. Among geolocated tweets, 76.2% were personal communications, 21.1% media, and 2.7% retail. About 71% of personal communication tweets expressed positive sentiment toward cannabis; 16% expressed negative sentiment. States in the recreational group had significantly greater average adjusted percentage of cannabis tweets (3.01%) compared with other groups. For personal communication tweets only, the recreational group (2.47%) was significantly greater than the medical, more restrictive (1.84%) and illegal (1.85%) groups. Similarly, the recreational group had significantly greater average positive-to-negative sentiment ratio (4.64) compared with the medical, more restrictive (4.15) and illegal (4.19) groups. Average adjusted percentages of unique users showed similar differences between recreational and other groups.Conclusions: States with less restrictive policies displayed greater cannabis-related tweeting and conveyed more positive sentiment. The study demonstrates the potential of Twitter data to become a valuable indicator of drug-related communications in the context of varying policy environments. [ABSTRACT FROM AUTHOR]

Aims: Several states in the U.S. have legalized cannabis for recreational or medical uses. In this context, cannabis edibles have drawn considerable attention after adverse effects were reported. This paper investigates Twitter users' perceptions concerning edibles and evaluates the association edibles-related tweeting activity and local cannabis legislation.Methods: Tweets were collected between May 1 and July 31, 2015, using Twitter API and filtered through the eDrugTrends/Twitris platform. A random sample of geolocated tweets was manually coded to evaluate Twitter users' perceptions regarding edibles. Raw state proportions of Twitter users mentioning edibles were ajusted relative to the total number of Twitter users per state. Differences in adjusted proportions of Twitter users mentioning edibles between states with different cannabis legislation status were assesed via a permutation test.Results: We collected 100,182 tweets mentioning cannabis edibles with 26.9% (n=26,975) containing state-level geolocation. Adjusted percentages of geolocated Twitter users posting about edibles were significantly greater in states that allow recreational and/or medical use of cannabis. The differences were statistically significant. Overall, cannabis edibles were generally positively perceived among Twitter users despite some negative tweets expressing the unreliability of edible consumption linked to variability in effect intensity and duration.Conclusion: Our findings suggest that Twitter data analysis is an important tool for epidemiological monitoring of emerging drug use practices and trends. Results tend to indicate greater tweeting activity about cannabis edibles in states where medical THC and/or recreational use are legal. Although the majority of tweets conveyed positive attitudes about cannabis edibles, analysis of experiences expressed in negative tweets confirms the potential adverse effects of edibles and calls for educating edibles-naïve users, improving edibles labeling, and testing their THC content. [ABSTRACT FROM AUTHOR]

The article examines the potential of U.S. President Donald Trump's protectionism to save the World Trade Organization (WTO). Topics covered include the importance of a WTO reform to create a fairer trading system that is aligned with 21st century conditions, the need for the WTO to address China's unfair trade practices, and the benefits of open trade.

Background Paroxysmal nocturnal haemoglobinuria ( PNH) is a rare, acquired, clonal haemopoietic stem cell disorder that causes chronic intravascular haemolysis, increases the risk of thrombosis and results in significant patient morbidity and mortality. The symptoms of PNH may have a major impact on patient quality of life. Aims To assess patient fatigue and health-related quality of life in 29 patients with PNH using the Functional Assessment of Chronic Illness Therapy Fatigue subscale version 4 ( FACIT-Fatigue) and the European Organization for Research and Treatment of Cancer Quality-of- Life Questionnaire-C30, version 3 ( EORTC QLQ-C30). Methods Following completion of the questionnaires, patients were interviewed to assess the validity, clarity, relevance and comprehensiveness of the assessments. Results Overall, patients considered both the FACIT-Fatigue and EORTC QLQ- C30 instruments to be relevant and adequate in assessing the level of PNH-associated fatigue and other quality-of-life measures. The FACIT- Fatigue questionnaire was considered to be clear and to comprehensively cover PNH-related fatigue. The EORTC QLQ- C30 instrument was considered to be easy to understand, but of an overall lower relevance, although some differences between countries were observed. Patients suggested additional questions that could be incorporated into future EORTC QLQ- C30 versions to make it more relevant to PNH. Conclusions This study confirms the validity of the FACIT-Fatigue and the EORTC QLQ- C30 questionnaires in this patient population and their routine use should be considered in the management of patients with PNH. [ABSTRACT FROM AUTHOR]

The article presents a speech by Pascal Lamy, Director-General of World Trade Organisation, delivered at the Informal Trade Negotiations Committee Meeting held on October 21, 2011 in which he focuses on the Doha Development Agenda. The Agenda is on the weighted down of trade and economic activity due to debt in the U.S. and Eurozone. Information on a cut forecasted in the global exports by the WTO and its impact on the financial markets of the developing countries are also presented.

This article presents arguments claiming that the periodical "Soldier of Fortune" can be read as an apocalyptic text which expresses a postmodern and secular form of the millennial myth. it is reported that the U.S.-led battle against so-called tyranny, or dictatorship, raged on at the 15th Anniversary Soldier of Fortune Convention and Exposition held in Las Vegas, Nevada, in September, 1990. The magazine and the subculture it represents is a postmodern expression of millenmalism which has surfaced in the U.S. in the final decades of the twentieth century. In the pages of the magazine, international conflict and the practice of survivalism are secular metaphors for the American millennial myth. Such metaphors, supposedly, allow subscribers to read into the confusing and rapidly changing events of the day their own often marginal social status and position. The millennial myth, reportedly, has been derived from ancient Hebrew and Christian apocalyptic literature concerning the ultimate destiny of the world and the cosmic cataclysm in which God destroys the ruling powers of evil and raises the righteous to life in a messianic kingdom.

The hybrid nature of convertible bonds continues to interest corporate financial man- agers, investors, and economists. While much theoretical and empirical research examines an issuer's choice between using straight debt and equity, little research evaluates how an issuer chooses among debt, equity, and convertible bonds. This study extends Marsh's [13) research on the differences between debt and equity issuers in the United Kingdom by examining U.S. industrial firms that issue debt, equity, or convertible bonds. It also illustrates how various distinguishing features influence the probability that each security will be issued. [ABSTRACT FROM AUTHOR]

This paper investigates the influence of the failure of Penn Square Bank of Oklahoma City on stock prices within the banking industry. This influence is compared to the results of previous studies of the failures of Franklin National Bank of New York and United States National Bank of San Diego. While each of these earlier studies finds only a transitory impact on bank securities, this paper finds evidence of a structural change in the pricing mechanism for bank stocks after the Penn Square failure. [ABSTRACT FROM AUTHOR]

The acute respiratory distress syndrome (ARDS), a process of non-hydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies carries a high morbidity, mortality (10-90%) and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged and may be different in Europe. Part of the reason for these uncertainties is the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those whose wish to know the true incidence and outcome on this clinical syndrome are stymied. The European American Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS. [ABSTRACT FROM AUTHOR]

Describes a successful effort at the University of Denver in Colorado which might serve as a model for other university programs in global or international education. Historical development of Center for Teaching International Relations; Graduate-credit and teacher inservice-training; Consulting services for schools and other educational agencies; Grants and special programs; Community education.

This article examines the marketing issues related to U.S. banks' compliance with the requirements of the Community Reinvestment Act and its associated regulations. It provides a general discussion of the impact of legislation and regulation on the marketing of financial services. As well, it looks at the Community Reinvestment Act and its implications for product development, promotion, distribution and pricing of banking services. Marketing concepts are discussed in the context of the development and marketing of Community Reinvestment Act products.

Discusses the appeal to the European Union and the U.S. to recognize their shared responsibility on providing international leadership. Information on the economic relationship of the European Union and the U.S.; Analysis on the similarities and differences of policies of the two regions; Discussion on the need to preserve the common interest of Europe and the U.S., to minimize their differences and maximize their joint influence for good.

The article talks about bilateral agreements on behalf of the U.S., an exchange agreement between two nations which gives each party favored trade status and sets purchase guarantees, remove tariffs, and other trade barrier barriers. It includes expectation of World Trade Organization (WTO) targeted by the U.S. in order to make bilateralism the new norm, based on belief of U.S. president Donald Trump's that the U.S. will always win in a bilateral trade confrontation.

The article discusses the wary form of globalization in the new era that emerged from the end of the post-Cold War years and the end of "naive globalization." It includes an in-depth analysis of the new vulnerabilities and opportunities carried by this new form of globalization, which is marked by U.S. efforts to spread democratization and modernization in the Arab Middle East as part of the fight against terrorism.

Aims: Media reports suggest increasing popularity of marijuana concentrates ("dabs"; "earwax"; "budder"; "shatter; "butane hash oil") that are typically vaporized and inhaled via a bong, vaporizer or electronic cigarette. However, data on the epidemiology of marijuana concentrate use remain limited. This study aims to explore Twitter data on marijuana concentrate use in the U.S. and identify differences across regions of the country with varying cannabis legalization policies.Methods: Tweets were collected between October 20 and December 20, 2014, using Twitter's streaming API. Twitter data filtering framework was available through the eDrugTrends platform. Raw and adjusted percentages of dabs-related tweets per state were calculated. A permutation test was used to examine differences in the adjusted percentages of dabs-related tweets among U.S. states with different cannabis legalization policies.Results: eDrugTrends collected a total of 125,255 tweets. Almost 22% (n=27,018) of these tweets contained identifiable state-level geolocation information. Dabs-related tweet volume for each state was adjusted using a general sample of tweets to account for different levels of overall tweeting activity for each state. Adjusted percentages of dabs-related tweets were highest in states that allowed recreational and/or medicinal cannabis use and lowest in states that have not passed medical cannabis use laws. The differences were statistically significant.Conclusions: Twitter data suggest greater popularity of dabs in the states that legalized recreational and/or medical use of cannabis. The study provides new information on the epidemiology of marijuana concentrate use and contributes to the emerging field of social media analysis for drug abuse research. [ABSTRACT FROM AUTHOR]

Background The LAAOS III (Left Atrial Appendage Occlusion Study) clinical trial demonstrated that concomitant left atrial appendage (LAA) occlusion leads to a lower risk of ischemic stroke or systemic embolism compared with no occlusion in participants with atrial fibrillation and a CHA 2 DS 2 -VASc score of ≥2 undergoing cardiac surgery for another indication. We report the cost implications of concomitant LAA occlusion during cardiac surgery. Methods and Results Using LAAOS III data, we compared the costs (in US dollars) associated with LAA occlusion to no occlusion from the perspective of the Centers for Medicare and Medicaid Services. We calculated the average cost per participant during the trial by applying Medicare reimbursement costs to cardiovascular events for all trial participants. We conducted sensitivity analyses, varying the cost of stroke ±25% and occlusion technique use. Cost neutrality was defined as a mean cost difference within ±5% of the cost per participant in the no-occlusion group. Total study cost per participant was $3878 in the LAA occlusion group and $4490 in the no-occlusion group, a mean difference of -$612 (95% CI, -$1276 to $45). The main drivers of cost savings were fewer stroke events during the trial (mean difference of -$1021). In sensitivity analyses, LAA occlusion was cost saving for suture and stapler techniques but more expensive with closure device. Conclusions Concomitant LAA occlusion was cost saving for participants in LAAOS III. Our findings support concomitant LAA occlusion as an economically dominant strategy for patients with atrial fibrillation and a CHA 2 DS 2 -VASc score of ≥2 undergoing cardiac surgery.

Objectives: The aim of this study was to examine the value of frailty to predict in-hospital major bleeding and determine its impact on mid-term mortality following transcatheter (TAVR) or surgical (SAVR) aortic valve replacement., Background: Bleeding complications are harbingers of mortality and major morbidity in patients undergoing TAVR or SAVR. Despite the high prevalence of frailty in this population, little is known about its effects on bleeding risk., Methods: A post hoc analysis was performed of the multinational FRAILTY-AVR (Frailty Aortic Valve Replacement) cohort study, which prospectively enrolled older adults ≥70 years of age undergoing TAVR or SAVR. Trained researchers assessed frailty using a questionnaire and physical performance battery pre-procedure and ascertained clinical data from the electronic health record. The primary endpoint was major or life-threatening bleeding during the index hospitalization, and the secondary endpoint was units of packed red blood cells transfused., Results: The cohort consisted of 1,195 patients with a mean age of 81.3 ± 6.0 years. The incidence of life-threatening bleeding, major bleeding with a clinically apparent source, and major bleeding without a clinically apparent source was, respectively, 3%, 6%, and 9% in the TAVR group and 8%, 10%, and 31% in the SAVR group. Frailty measured using the Essential Frailty Toolset was an independent predictor of major bleeding and packed red blood cell transfusions in both groups. Major bleeding was associated with a 3-fold increase in 1-year mortality following TAVR (odds ratio: 3.40; 95% confidence interval: 2.22 to 5.21) and SAVR (odds ratio: 2.79; 95% confidence interval: 1.25 to 6.21)., Conclusions: Frailty is associated with post-procedural major bleeding in older adults undergoing TAVR and SAVR, which is in turn associated with a higher risk for mid-term mortality., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) found that rosuvastatin alone or with candesartan and hydrochlorothiazide (HCT) (in a subgroup with hypertension) significantly lowered cardiovascular events compared with placebo in 12 705 individuals from 21 countries at intermediate risk and without cardiovascular disease. We assessed the costs implications of implementation in primary prevention in countries at different economic levels., Methods and Results: Hospitalizations, procedures, study and non-study medications were documented. We applied country-specific costs to the healthcare resources consumed for each patient. We calculated the average cost per patient in US dollars for the duration of the study (5.6 years). Sensitivity analyses were also performed with cheapest equivalent substitutes. The combination of rosuvastatin with candesartan/HCT reduced total costs and was a cost-saving strategy in United States, Canada, Europe, and Australia. In contrast, the treatments were more expensive in developing countries even when cheapest equivalent substitutes were used. After adjustment for gross domestic product (GDP), the costs of cheapest equivalent substitutes in proportion to the health care costs were higher in developing countries in comparison to developed countries., Conclusion: Rosuvastatin and candesartan/HCT in primary prevention is a cost-saving approach in developed countries, but not in developing countries as both drugs and their cheapest equivalent substitutes are relatively more expensive despite adjustment by GDP. Reductions in costs of these drugs in developing countries are essential to make statins and blood pressure lowering drugs affordable and ensure their use., Clinical Trial Registration: HOPE-3 ClinicalTrials.gov number, NCT00468923., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: The authors sought to determine whether frail older adults undergoing nonfemoral transcatheter aortic valve replacement (TAVR) procedures had a higher risk of 30-day and 12-month mortality., Background: Frailty can help predict outcomes and guide therapy in older adults being considered for TAVR. Nonfemoral TAVR procedures are more invasive and impart a greater risk of adverse events, which may be less well tolerated in frail patients, compared with transfemoral TAVR procedures., Methods: This study was a post hoc analysis of the FRAILTY-AVR (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions) prospective multicenter cohort that consisted of older adults undergoing TAVR from 2012 to 2017. Frailty was assessed using the Essential Frailty Toolset (EFT). Endpoints of interest were 30-day and 12-month all-cause mortality. Interaction tables and multivariable logistic regression models were used to investigate statistical interaction on the additive and multiplicative scales., Results: The cohort consisted of 723 patients with a mean age of 84 ± 6 years, of which 556 (77%) had femoral access and 167 (23%) had nonfemoral access. In frail patients with EFT scores ≥3 (35%), nonfemoral access was associated with increased 30-day mortality (odds ratio [OR]: 3.91; 95% confidence interval [CI]: 1.48 to 10.31); whereas in nonfrail patients with EFT scores <3 (65%), nonfemoral access had no effect (OR: 1.29; 95% CI: 0.34 to 4.94). There was statistical evidence of interaction between frailty and access site on 30-day mortality on the additive scale (relative excess risk due to interaction = 5.95). Nonfemoral access was associated with increased 1-year mortality in frail patients (OR: 1.98; 95% CI: 1.00 to 3.93) but not in nonfrail patients (OR: 1.83; 95% CI: 0.90 to 3.74), although there was no statistical evidence of interaction., Conclusions: Frail patients undergoing TAVR via a more invasive nonfemoral access face a substantially higher risk of 30-day mortality, whereas nonfrail older adults tolerate the procedure with a low short-term risk irrespective of access route., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Timing of Intervention in Acute Coronary Syndromes (TIMACS) trial demonstrated that early invasive intervention (within 24 hours) was similar to a delayed approach (after 36 hours) overall but improved outcomes were seen in patients at high risk. However, the cost implications of an early versus delayed invasive strategy are unknown., Methods and Results: A third-party perspective of direct cost was chosen and United States Medicare costs were calculated using average diagnosis related grouping (DRG) units. Direct medical costs included those of the index hospitalization (including clinical, procedural and hospital stay costs) as well as major adverse cardiac events during 6 months of follow-up. Sensitivity and sub-group analyses were performed. The average total cost per patient in the early intervention group was lower compared with the delayed intervention group (-$1170; 95% CI -$2542 to $202). From the bootstrap analysis (5000 replications), the early invasive approach was associated with both lower costs and better clinical outcomes regarding death/myocardial infarction (MI)/stroke in 95.1% of the cases (dominant strategy). In high-risk patients (GRACE score ≥141), the net reduction in cost was greatest (-$3720; 95% CI -$6270 to -$1170). Bootstrap analysis revealed 99.8% of cases were associated with both lower costs and better clinical outcomes (death/MI/stroke)., Limitations: We were unable to evaluate the effect of community care and investigations without hospitalization (office visits, non-invasive testing, etc). Medication costs were not captured. Indirect costs such as loss of productivity and family care were not included., Conclusions: An early invasive management strategy is as effective as a delayed approach and is likely to be less costly in most patients with acute coronary syndromes.

Background: The HOPE study has demonstrated that ramipril is beneficial (ie, prevents cardiovascular death, myocardial infarction, and stroke) for a broad range of patients without evidence of left ventricular dysfunction or heart failure who are at high risk for cardiovascular event. In this study, we report the cost implications, in both the United States and Canada, of the use of ramipril after the HOPE study., Methods and Results: A third-party perspective was chosen (Medicare for the United States and Ministry of Health for Canada). We calculated the costs of the management strategies of ramipril and placebo. An annual discount rate of 3% was used over the 4.5 years of follow-up. Sensitivity analyses were performed. Costs are reported in United States dollars and in Canadian dollars, respectively. The total costs per patient (including acquisition costs of ramipril) were not different between the groups in both countries (United States, $13 520 versus $13 631; Canada, $8702 versus $8588). From the distribution of cases in the bootstrap analysis, we found that 90% of cases fall either into a cost-neutral or cost-saving situation (64% in United States and 27% in Canada) or into a cost-effectiveness situation with an incremental cost-effectiveness ratio <$10 000 (in respective currency) per primary event saved., Conclusions: On the basis of these results, we suggest that the use of ramipril is likely to represent an efficient use of resources in both countries. These findings support the use of ramipril in populations included in the HOPE study.