Carolin M. Frey

Incidence of intracranial hemorrhage complicating treatment with glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis of major clinical trials

PURPOSE The major risk of therapy with platelet glycoprotein IIb/IIIa receptor inhibitors is bleeding. We reviewed trials using these agents to determine if bleeding risks include an increased incidence of intracranial hemorrhage. METHODS A Medline search identified 14 randomized trials of intravenous platelet glycoprotein IIb/IIIa receptor inhibitors for patients undergoing percutaneous coronary intervention or who had an acute coronary syndrome. We compared the incidence of intracranial hemorrhage among 15,850 patients treated with glycoprotein IIb/IIIa inhibitors with that among 12,039 patients treated with placebo. RESULTS The incidence of intracranial hemorrhage with heparin plus any IIb/IIIa inhibitor was similar to placebo with heparin (0.12% vs 0.09%, odds ratio = 1.3, 95% confidence interval: 0.6 to 3.1, P = 0.59). The incidence of intracranial hemorrhage with glycoprotein IIb/IIIa drugs alone was similar to that with heparin alone (0.07% vs 0.06%), albeit with a wide confidence interval (odds ratio = 1.2, 95% confidence interval: 0.1 to 16, P = 1.0). CONCLUSIONS Intravenous glycoprotein IIb/IIIa receptor inhibitors alone or in combination with heparin do not cause a statistically significant excess of intracranial hemorrhage as compared with heparin alone. Because of small numbers, the data do not exclude the possibility of an excess of intracranial hemorrhage in some groups of patients treated with glycoprotein IIb/IIIa receptor inhibitors.

Parametric relative survival regression using generalized linear models with application to Hodgkin's lymphoma

Summary. Changes in survival rates during 1940-1992 for patients with Hodgkins disease are studied by using population-based data. The aim of the analysis is to identify when the breakthrough in clinical trials of chemotherapy treatments started to increase population survival rates, and to find how long it took for the increase to level off, indicating that the full population effect of the breakthrough had been realized. A Weibull relative survival model is used because the model parameters are easily interpretable when assessing the effect of advances in clinical trials. However, the methods apply to any relative survival model that falls within the generalized linear models framework. The model is fitted by using modifications of existing software (SAS, GLIM) and profile likelihood methods. The results are similar to those from a cause-specific analysis of the data by Feuer and co-workers. Survival started to improve around the time that a major chemotherapy breakthrough (nitrogen mustard, Oncovin, prednisone and procarbazine) was publicized in the mid1 960s but did not level off for 1 1 years. For the analysis of data where the cause of death is obtained from death certificates, the relative survival approach has the advantage of providing the necessary adjustment for expected mortality from causes other than the disease without requiring information on the causes of death.

Importance of supplemental vitamin C in determining serum ascorbic acid in controls from a cervical cancer case‐control study: Implications for epidemiological studies

Classification of individuals by their vitamin C intake was investigated in 493 control subjects from a cervical cancer case-control study. The influence of dietary and supplemental sources of vitamin C, as well as demographic and life-style factors, on serum ascorbic acid were examined. Usual dietary intakes of vitamin C were determined from a food frequency questionnaire and recent intakes from a 24-hour recall taken at the time of blood collection. Vitamin supplement information was obtained at both times. In a regression analysis, the factors found to predict serum ascorbic acid were total recent vitamin C intake, an indicator variable for supplement use, body mass index, number of cigarettes smoked per day, race, education, and age. Higher levels of serum ascorbic acid were found among older nonsmoking highly educated leaner white women. Consideration of supplements, in addition to dietary sources of vitamin C, improved correlation coefficients between serum ascorbic acid and usual vitamin C intake from 0.19 to 0.32 and between serum ascorbic acid and recent intake from 0.36 to 0.56. Furthermore, whereas only a twofold difference between the first and fourth quartiles of serum ascorbic acid was observed using recent dietary vitamin C without supplements, this range increased to sixfold with addition of supplement data. Epidemiological studies should consider use of total vitamin C intakes from supplement and food sources to permit accurate classification of individuals.

A BOOTSTRAP TEST OF THE GOODNESS-OF-FIT OF THE MULTIVARIATE TOLERANCE MODEL

The multivariate tolerance (MT) model is used to model multi-agent bioassay survival responses. When the MT model is appropriate, it can aid in identifying the biological mechanism of the survival response or motivate tolerance-based error reduction. A bootstrap test for the goodness-of-fit of the MT model is proposed. The proposed test has little level error, useful power, and makes a novel adjustment for the multiple testing character of the question of MT model goodness-of-fit. This adjustment may be more generally applicable in bootstrap testing.