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In this clinical trial involving patients undergoing high-risk cardiac surgery, aprotinin was somewhat more effective than either aminocaproic acid or tranexamic acid in reducing massive perioperative bleeding but at the expense of a higher rate of death, mainly from cardiac causes. Aprotinin cannot be recommended to control blood loss in this clinical setting. In patients undergoing high-risk cardiac surgery, aprotinin was somewhat more effective than either aminocaproic acid or tranexamic acid in reducing massive perioperative bleeding but at the expense of a higher rate of death, mainly from cardiac causes. Every year an estimated 1 million to 1.25 million patients worldwide undergo cardiac surgery, including high-risk procedures such as repeat coronary-artery bypass grafting (CABG), valve replacements, and combined procedures. 1 High-risk procedures present an increased risk of death, massive bleeding, renal failure, and thrombotic complications, as compared with first-time isolated CABG. 2 – 4 Three antifibrinolytic agents have been used in cardiac surgery to minimize bleeding and reduce the need for transfusion: aprotinin, a naturally occurring serine protease inhibitor, and two lysine analogues, tranexamic acid and aminocaproic acid. 5 In clinical trials, all three drugs have been shown to be effective in reducing the . . .

The antifibrinolytic agent aprotinin is often used to control blood loss in patients undergoing cardiac surgery. This observational study found that the use of aprotinin is associated with an increased risk of serious end-organ damage. In patients undergoing cardiac surgery, aprotinin should be replaced by aminocaproic acid or tranexamic acid. Aprotinin is often used to control blood loss in patients undergoing cardiac surgery. This observational study found that the use of aprotinin is associated with an increased risk of serious end-organ damage. The mainstay of medical therapy for patients with an acute coronary syndrome — when accompanied by myocardial infarction with ST-segment elevation — includes fibrinolytic and antiplatelet agents to mitigate thrombosis-related events. 1 However, if surgical therapy (coronary-artery surgery) is elected, fibrinolytic agents are not used before, during, or after surgery because of concerns regarding excessive bleeding. In fact, these bleeding-related concerns have given rise to the testing, regulatory approval, and widespread use of two classes of agents, both proven to mitigate bleeding: the lysine analogues (aminocaproic acid and tranexamic acid) and the serine protease inhibitors (aprotinin). Consequently, the majority of patients . . .

In this single-center study, the use of aprotinin in coronary-artery bypass grafting (CABG) was associated with an increase in mortality and worsening renal function. The results concur with those of Schneeweiss et al. in this issue of the Journal, and together these studies raise concern about the safety of aprotinin in CABG. In this single-center study, the use of aprotinin in coronary-artery bypass grafting was associated with an increase in mortality and worsening renal function. Aprotinin (Trasylol, Bayer HealthCare) is an antifibrinolytic agent in widespread use during cardiac surgery around the world, particularly in high-risk patients. Aprotinin was approved by the Food and Drug Administration on December 29, 1993, for use during cardiac surgery, to reduce the risk of blood transfusion. The literature on aprotinin contains reports of single studies ranging in size from 22 patients 1 to 12,403 patients, 2 as well as several meta-analyses and systematic reviews. Dozens of clinical trials have been conducted with this agent since the original report of efficacy of the high-dose regimen was published, 1 yet, as pointed out in a . . .

Aprotinin (Trasylol) is used to control bleeding during coronary-artery bypass grafting (CABG), but in this observational study, there was an increased risk of in-hospital death when this drug was used, as compared with when aminocaproic acid was used. These data concur with those of Shaw et al. in this issue of the Journal and, in conjunction with those from previous studies, call into question the safety of aprotinin use in patients undergoing CABG. Aprotinin (Trasylol) is used to control bleeding during coronary-artery bypass grafting. In this observational study, there was an increased risk of in-hospital death when this drug was used, as compared with when aminocaproic acid was used. The administration of aprotinin (Trasylol, Bayer HealthCare) during cardiac surgery reduces blood loss and preserves platelet function. 1 , 2 A recent international study of over 4000 patients undergoing coronary-artery bypass grafting (CABG) showed a 59% increase in the risk of in-hospital death (relative risk, 1.59; 95% confidence interval [CI], 0.76 to 3.34) in aprotinin recipients as compared with nonrecipients 3 and a higher 5-year mortality among aprotinin recipients (relative risk, 1.48; 95% CI, 1.13 to 1.93). 4 A meta-analysis of trials and a single-center observational study showed less worrisome results, though both lacked the statistical power of the earlier studies. 5 , 6 Most recently, . . .

Von Willebrand's disease is an inherited bleeding disorder with a prevalence as high as 1 to 2 percent in the general population, according to screening studies. However, its prevalence is deemed to be only 30 to 100 cases per million on the basis of symptomatic referrals, a prevalence that is similar to that of hemophilia A. This article discusses major advances in our understanding of the pathophysiology, molecular basis, and management of von Willebrand's disease. A review of the major advances in understanding of the pathophysiology, molecular basis, and management of von Willebrand's disease. Von Willebrand's disease is an inherited bleeding disorder with a prevalence as high as 1 to 2 percent in the general population, according to screening studies. 1 , 2 In contrast, estimates based on referral for symptoms of bleeding suggest a prevalence of 30 to 100 cases per million, which is similar to the prevalence of hemophilia A. 1 , 2 The disease was first described in 1926 by the Finnish pediatrician Erik von Willebrand, who used a rowboat to make house calls to patients with the disease in the Åland archipelago. The disease is caused by the quantitative deficiency or dysfunction of von . . .

When bleeding is the consequence of a specific defect of hemostasis, the goal of treatment is to correct the defect. A typical example is the replacement of factor VIII by transfusion in patients with hemophilia. Specific treatment may be impossible, however, because bleeding may result from multiple defects or because no cause can be identified. In such situations, nontransfusional drugs that help to stop bleeding are indicated. 1 These drugs may also be indicated for patients who refuse blood transfusion or for those who undergo surgical procedures associated with large blood losses necessitating many transfusions of donated blood. Many nontransfusional hemostatic . . .

To illustrate that matching on provider may exacerbate, not remove, bias. The degree of confounding bias depends in part on the proportions of treatment variation that can be ascribed to confounders and to instruments, respectively. This commentary raises the specific example of bias by matching on hospital induced in a study of coronary artery bypass graft surgery patients and illustrates the effect of matching on provider in a constructed example. Matching on provider removes a “benign” source of treatment variability, leaving unmeasured confounders as potentially the most important determinants of treatment. Researchers need to articulate the presumed source of pseudorandom variation in observational studies and need to take care not to reduce their effect through unnecessary control.

Twenty-four patients with refractory epilepsy on one or more antiepileptic drugs were given additional vigabatrin (1 g twice daily for six weeks, followed by 1.5 g twice daily for a further six weeks) and matched placebo in a double blind, randomised, crossover study. A battery of neuropsychological tests was administered at baseline and at weeks two, six and 12 of both treatment periods. No significant differences were found between vigabatrin and placebo at any time point for any of the objective tests of cognitive function. Patients, however, reported a greater degree of sedation after two and six weeks on vigabatrin than during the equivalent placebo phase (p < 0.01), although no such difference was apparent at 12 weeks. Follow up over a mean of 14.75 months in 12 responders, who continued on vigabatrin, revealed a significant improvement (all p < 0.01) on each of three composite scales (three psychomotor tests, four memory tests, three self rating scales) compared with their scores during the double blind trial. Vigabatrin did not cause cognitive impairment either acutely or in the long term. Phased introduction, however, seems a prudent policy to allow tolerance to early subjective sedation.

Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin). Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery. We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0·55 [95% CI 0·34-0·90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0·37 [0·25-0·55], and 0·44 [0·22-0·90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2·4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results. Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.

Vigabatrin is a selective, irreversible suicide inhibitor of GABA transaminase and thus increases brain and CSF GABA. In 33 adult patients with long standing refractory epilepsy on treatment with one or two standard anti-convulsant drugs, the addition of vigabatrin up to 3g daily for eight weeks was associated with a 48.2% reduction in seizure frequency. Twenty patients who had exhibited a 50% or more reduction in frequency of one or more seizure types entered an eight week double-blind placebo controlled phase. Patients on vigabatrin maintained a 54.7% reduction of seizure frequency, whereas those on placebo showed an 18.6% increase in seizure frequency, a highly significant difference between the two groups. In the open phase, seven patients were withdrawn due to unacceptable and reversible adverse events. The commonest side effects were drowsiness, depression and mood instability, and headaches. Vigabatrin is a potentially valuable new treatment for chronic epilepsy, especially partial seizures with or without secondary generalisation.