A critical appraisal of platelet glycoprotein IIb/IIIa inhibition

AbstractDespite the success of abciximab in preventing ischemic events after percutaneous coronary interventions, attempts to develop intravenous, small-molecule glycoprotein IIb/IIIa antagonists and diversify the clinical indications for these agents have produced varied results. The 30-day ischemic event reduction in the percutaneous coronary intervention trials has ranged by over three-fold (16% to 56%) and is greater among the acute coronary syndrome trials. The phase III trials exploring the role of oral glycoprotein IIb/IIIa inhibition have been consistently disappointing, with evolving evidence of increased mortality. Mechanisms contributing to these heterogeneous results may include normal variation in platelet or receptor number, differences in receptor activity, interpatient variation in pharmacological dose-response and the possibility of prothrombotic or nonglycoprotein IIb/IIIa effects. Plausibility of “suboptimal” effect is suggested by several recent studies. Trials investigating the role of intravenous small-molecule IIb/IIIa antagonists highlight the importance of effective dosing. The increase in bleeding and mortality observed in the oral glycoprotein IIb/IIIa studies indicate the consequences of suboptimal dosing on safety on one hand, while raising the possibility of important prothrombotic, counterregulatory or other sudden cardiac events. This article will undertake a review of the relevant platelet biology, discuss the mechanisms that may contribute to suboptimal antiplatelet efficacy with these agents and examine insights from the clinical trials supporting these concepts

Disentangling Risk and Change: Internal and External Social Comparison in the Mutual Fund Industry

Using data on 3,225 actively managed U.S. mutual funds from 1980 to 2006, we test hypotheses designed to disentangle risk and change as outcomes of behavioral performance feedback routines. We theorize that managers make decisions involving risk and decisions involving change under different conditions and motivated by different concerns. Our results show internal social comparison across units within a firm will motivate risk, whereas external social comparison across firms will motivate change. When a fund experiences a performance shortfall relative to internal social comparison, the manager is likely to make decisions that involve risk because the social and spatial proximity of internal comparisons trigger individual concern and fear of negative individual consequences, such as job loss. In contrast, when a fund experiences a performance shortfall in comparison with external benchmarks, the manager is more likely to consider the shortfall an organizational concern and make changes that do not necessarily involve risk. Although we might assume that negative performance in comparison with both internal and external benchmarks would spur risky change, our results indicate that risky change occurs most often when a decision maker receives unfavorable internal social performance feedback and favorable external social performance feedback. By questioning assumptions about why and when organizational change involves risk, this study begins to separate change and risk outcomes of the decision-making process

Accounting Profession in Singapore; Professional Accounting in Foreign Country Series

https://egrove.olemiss.edu/aicpa_guides/1692/thumbnail.jp

Dialogue as Renounced Aggression: JMI and the Case of AOM\u27s President\u27s Response to EO13769

Dialogue and debate are at the core of the social sciences. In this piece, the Journal of Management Inquiry(JMI) editors-in-chief discuss their position and decisions pertaining to the publication of Professor Anita McGahan’s response to Professor Hardimos Tsoukas. A key decision—given JMI’s commitment to dialogue and exchange in its scholarly form—included publishing three curated pieces where renowned scholars applied their scholarly voice and expertise to McGahan’s historical narrative. To conclude this piece and the entire Editors’ Choice collection, five scholars speak to needed qualitative research standards or address McGahan’s leadership directly. Specific corrections to Tsoukas are also provided

Mortality benefit of beta-blockade after successful elective percutaneous coronary intervention

AbstractObjectivesThe goal of this study was to evaluate the mortality benefit of beta-blockers after successful percutaneous coronary intervention (PCI).BackgroundBeta-blockers reduce mortality after myocardial infarction (MI), though limited data are available regarding their role after successful PCI.MethodsEach year from 1993 through 1999, the first 1,000 consecutive patients undergoing PCI were systematically followed up. Patients presenting with acute or recent MI, shock, or unsuccessful revascularization procedures were excluded from the analysis. Clinical, procedural, and follow-up data of beta-blocker-treated and non-beta-blocker-treated patients were compared. A multivariate survival analysis model using propensity analysis was used to adjust for heterogeneity between the two groups.ResultsOf the 4,553 patients, 2,056 (45%) were treated with beta-blockers at the time of the procedure. Beta-blocker therapy was associated with a mortality reduction from 1.3% to 0.8% at 30 days (p = 0.13) and a reduction from 6.0% to 3.9% at one year (p = 0.0014). This survival benefit of beta-blockers was independent of left ventricular function, diabetic status, history of hypertension, or history of MI. Using propensity analysis, beta-blocker therapy remained an independent predictor for one-year survival after PCI (hazard ratio, 0.63; 95% confidence interval, 0.46 to 0.87; p = 0.0054).ConclusionsWithin this large prospective registry, beta-blocker use was associated with a marked long-term survival benefit among patients undergoing successful elective percutaneous coronary revascularization

The duration of pretreatment with ticlopidine prior to stenting is associated with the risk of procedure-related non–Q-wave myocardial infarctions

AbstractObjectives. This study sought to determine whether the duration of pretreatment with the adenosine diphosphate receptor antagonist ticlopidine prior to intracoronary stenting is associated with the incidence of procedure-related non–Q-wave myocardial infarctions (MIs).Background. Dual antiplatelet therapy with ticlopidine and aspirin is routinely used with stenting, although ticlopidine is commonly not begun until the day of the procedure. Periprocedural MIs are at least partially platelet-dependent events. As the maximal platelet inhibitory effects of this drug take 2 to 3 days to be realized, we hypothesized that longer treatment prior to stenting would be associated with lower rates of procedure-related MIs.Methods. We reviewed outcomes in 175 consecutive patients treated with ticlopidine prior to stenting at the Cleveland Clinic Foundation. Those patients with an elevation in creatine kinase above our laboratory normal (>210 IU/L) with ≥4% MB fraction on routine evaluation were defined as having a non–Q-wave MI.Results. There were 28 patients (16%) who had a non–Q-wave MI. Longer duration of ticlopidine pretreatment was strongly associated with a lower incidence of procedure-related non–Q-wave MIs (duration of pretreatment <1 day, 29% had MI; 1 to 2 days, 14%; ≥3 days, 5%; chi-square for trend = 9.6; p = 0.002). Ticlopidine pretreatment of ≥3 days was associated with a significant reduction in the risk of non–Q-wave MI (unadjusted odds ratio 0.18, 95% confidence interval = 0.04 to 0.78, p = 0.01) compared with pretreatment of <3 days.Conclusions. Among patients undergoing intracoronary stenting, beginning ticlopidine therapy several days prior to the procedure is associated with a reduced risk of procedural non–Q-wave MIs

Isolated right ventricular failure in hyperthyroidism: a clinical dilemma

We present a unique case of a 42-year-old gentleman with newly diagnosed Graves’ disease and isolated right ventricular failure. Extensive evaluation to include echocardiogram and cardiac catheterization were negative for significant pulmonary hypertension or coronary artery disease as potential etiologies. Hyperthyroid induced vasospasm is a rare but reported clinical entity that serves to be a clinical and diagnostic dilemma