Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis.

Ibrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B-cell malignancies. In ibrutinib clinical studies, low-grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N = 1768), including 4 randomised controlled trials (RCTs). Rates of any-grade bleeding were similar for single-agent ibrutinib and ibrutinib combinations (39% and 40%). Low-grade bleeding was more common in ibrutinib-treated than comparator-treated patients (35% and 15%), and early low-grade bleeding was not associated with MH. The proportion of MH in RCTs was higher with ibrutinib than comparators (4.4% vs. 2.8%), but after adjusting for longer exposure with ibrutinib (median 13 months vs. 6 months), the incidence of MH was similar (3.2 vs. 3.1 per 1000 person-months). MH led to treatment discontinuation in 1% of all ibrutinib-treated patients. Use of anticoagulants and/or antiplatelets (AC/AP) during the study was common (~50% of patients) and had an increased exposure-adjusted relative risk for MH in both the total ibrutinib-treated population (1.9; 95% confidence interval, 1.2-3.0) and RCT comparator-treated patients (2.4; 95% confidence interval, 1.0-5.6), indicating that ibrutinib may not alter the effect of AC/AP on the risk of MH in B-cell malignancies.

A brief but comprehensive lifestyle education program based on yoga reduces risk factors for cardiovascular disease and diabetes mellitus.

OBJECTIVES: The objective of the study was to study the short-term impact of a brief lifestyle intervention based on yoga on some of the biochemical indicators of risk for cardiovascular disease and diabetes mellitus. DESIGN: The variables of interest were measured at the beginning (day 1) and end (day 10) of the intervention using a pre-post design. SETTING: The study is the result of operational research carried out in our Integral Health Clinic (IHC). The IHC is an outpatient facility which conducts 8-day lifestyle modification programs based on yoga for prevention and management of chronic disease. A new course begins every alternate week of the year. SUBJECTS: The study is based on data collected on 98 subjects (67 male, 31 female), ages 20-74 years, who attended one of our programs. The subjects were a heterogeneous group of patients with hypertension, coronary artery disease, diabetes mellitus, and a variety of other illnesses. INTERVENTION: The intervention consisted of asanas (postures), pranayama (breathing exercises), relaxation techniques, group support, individualized advice, lectures and films on the philosophy of yoga and the place of yoga in daily life, meditation, stress management, nutrition, and knowledge about the illness. OUTCOME MEASURES: The outcome measures were fasting plasma glucose and serum lipoprotein profile. These variables were determined in fasting blood samples, taken on the first and last day of the course. RESULTS: Fasting plasma glucose, serum total cholesterol, low-density lipoprotein (LDL) cholesterol, very- LDL cholesterol, the ratio of total cholesterol to high density lipoprotein (HDL) cholesterol, and total triglycerides were significantly lower, and HDL cholesterol significantly higher, on the last day of the course compared to the first day of the course. The changes were more marked in subjects with hyperglycemia or hypercholesterolemia. CONCLUSIONS: The observations suggest that a short lifestyle modification and stress management education program leads to favorable metabolic effects within a period of 9 days.