Effectiveness and Safety of Ibrutinib for Chronic Lymphocytic Leukemia in Routine Clinical Practice: 3-Year Follow-up of the Belgian Ibrutinib Real-World Data (BiRD) Study.

The multicenter observational BiRD study investigated the real-world effectiveness and safety of ibrutinib in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia (WM) in Belgium. This interim analysis reports results for patients with CLL, with a median follow-up of 34 months. Overall, patients had predominantly relapsed/refractory disease (73%) and were elderly (median age 72 years) with high-risk features such as del17p and/or TP53 mutations (59%). Patients were included either prospectively or retrospectively, and the total patient population effectiveness results were adjusted with left truncation. In the effectiveness population (N = 221: prospective, n = 71; retrospective, n = 150), the overall response rate was 90.0%. Median progression-free survival was 38.3 months (prospective, not estimable; retrospective, 51.5 months) and median overall survival was not yet estimable in the total, prospective and retrospective groups. Treatment-emergent adverse events (TEAEs) for the prospective and retrospective groups are reported separately. Any-grade TEAEs of interest in the prospective/retrospective groups included infections (67.1%/60.1%), diarrhea (20.5%/10.5%), hypertension (16.4%/9.8%) and atrial fibrillation (12.3%/7.2%). Major bleeding was reported in 5.5%/3.3% of prospective/retrospective patients, with little difference observed between those receiving versus not receiving antithrombotic treatment. Discontinuations due to toxicity were reported in 10.5% of patients. Results from this interim analysis show treatment with ibrutinib to be effective and tolerable, with no new safety signals observed. Future analyses will report on longer-term follow-up.

Long-acting risperidone compared with oral olanzapine and haloperidol depot in schizophrenia: a Belgian cost-effectiveness analysis.

Patients with schizophrenia suffer numerous relapses and rehospitalizations that are associated with high direct and indirect medical expense. Suboptimal therapeutic efficacy and, in particular, problems with compliance are major factors leading to relapse. Atypical antipsychotic agents offer improved efficacy and a lower rate of extrapyramidal adverse effects compared with conventional antipsychotic drugs. Long-acting intramuscular risperidone combines these benefits with improvements in compliance associated with depot injections. To assist decision making regarding the place of long-acting risperidone in therapy, a cost-effectiveness analysis of strategies involving first-line treatment with long-acting risperidone, oral olanzapine or depot haloperidol was performed from the perspective of the Belgian healthcare system. A decision tree model was created to compare the cost effectiveness of three first-line treatment strategies in a sample of young schizophrenic patients who had been treated for 1 year and whose disease had not been diagnosed for longer than 5 years. The model used a time horizon of 2 years, with health state transition probabilities, resource use and cost estimates derived from clinical trials, expert opinion and published prices. The four health states in the model were derived from an analysis of the literature. The principal efficacy measure was the proportion of patients successfully treated, defined as those who responded to initial treatment and who had none to two episodes of clinical deterioration without needing a change of treatment over the 2-year period. Comprehensive sensitivity analysis was carried out to test the robustness of the model. A greater proportion of patients were successfully treated with long-acting risperidone (82.7%) for 2 years, compared with those treated with olanzapine (74.8%) or haloperidol (57.3%). Total mean costs per patient over 2 years were 16,406 Euro with long-acting risperidone, 17,074 Euro with olanzapine and 21,779 Euro with haloperidol (year of costing 2003). The mean cost-effectiveness ratios were 19,839 Euro, 22,826 Euro and 38,008 Euro per successfully treated patient for long-acting risperidone, olanzapine and haloperidol, respectively. Results of the sensitivity analysis confirmed that the results were robust to a wide variation of different input variables (effectiveness, dosing distribution, patient status according to healthcare system). Long-acting risperidone was the dominant strategy, being both more effective and less costly than either oral olanzapine or depot haloperidol. Long-acting risperidone appears to represent a favourable first-line strategy for patients with schizophrenia requiring long-term maintenance treatment.

Morphological and mechanical determinants of bite force in bats: do muscles matter?

Bats are one of the most diverse groups of mammals and have radiated into a wide variety of trophic niches. Accordingly, the cranial structure in bats is unusually variable among mammals and thought to reflect specializations for feeding and echolocation. However, recent analyses of cranial structure, feeding behavior and bite force across a wide range of bats suggest that correlations between morphology and performance and/or ecology are not as clearcut as previously thought. For example, most of the variation in bite force across a wide range of phyllostomid bats was explained by differences in body size rather than specific cranial traits. However, remarkably little is known about the muscular components that are responsible for generating the actual bite forces. We have tested which aspects of the cranial muscular system are good predictors of bite force across a wide range of species using a modeling approach. Model calculations of bite force show good correspondence with in vivo data suggesting that they can be used to estimate performance of the cranial system. Moreover, our data show that bite force is strikingly well explained by differences in temporalis muscle mass, temporalis fiber length and masseter muscle mass. Moreover, our data show that evolutionary changes in bite force capacity in bats are associated with evolutionary changes in relative m. temporalis mass and absolute skull length.