Cost-Effectiveness of Bosutinib for the Treatment of Adult Patients with Chronic Phase Chronic Myeloid Leukemia in the Second-Line Setting

Background A recently conducted matching-adjusted indirect comparison demonstrated that bosutinib improved progression-free survival, and delayed progression to advanced disease compared with dasatinib and nilotinib in patients with second line (2L) chronic-phase chronic myeloid leukemia (CP-CML). However, the long-term clinical and economic impact of using bosutinib versus dasatinib and nilotinib has not been evaluated. The objective was to determine the cost-effectiveness of bosutinib compared with dasatinib and bosutinib compared with nilotinib from a US payer perspective. Methods A cost-effectiveness model was developed using partition survival methods and three health states: progression-free, progression, and death. Trial data (individual patient-level and aggregate-level data) informed the progression-free and overall survival estimates. Costs included drugs and medical resource use. Utility values were obtained from literature. Sensitivity analyses (SAs) included one-way and probabilistic sensitivity analyses (PSAs). Results Comparing bosutinib versus dasatinib resulted in a gain of 0.4 discounted life years, 1.5 quality-adjusted life years (QALYs), and incremental costs of $28,459 (values in 2020 US dollars), for an incremental cost-effectiveness ratio (ICER) of$19,811/QALY gained. Comparing bosutinib versus nilotinib resulted in a gain of 0.8 discounted life-years, 1.8 QALYs, and incremental costs of $76,563, for an ICER of$41,932/QALY gained. Drug costs and extrapolation distribution type were the main drivers of the model in the one-way SAs. In the PSAs, bosutinib had >90% and >80% probabilities of being cost-effective at a willingness-to-pay threshold of $100,000/QALY versus dasatinib and nilotinib, respectively. Conclusions Our results suggest that compared with dasatinib and nilotinib, bosutinib may represent good value for money for treating 2L CP-CML patients

An Embarrassingly Simple Method to Mitigate Undesirable Properties of Pretrained Language Model Tokenizers

We introduce FLOTA (Few Longest Token Approximation), a simple yet effective method to improve the tokenization of pretrained language models (PLMs). FLOTA uses the vocabulary of a standard tokenizer but tries to preserve the morphological structure of words during tokenization. We evaluate FLOTA on morphological gold segmentations as well as a text classification task, using BERT, GPT-2, and XLNet as example PLMs. FLOTA leads to performance gains, makes inference more efficient, and enhances the robustness of PLMs with respect to whitespace noise

Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny.

The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ, combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium.This work was supported by a grant from the Medical Research Council programme grant no. MR/J001023/1 (B.L-L. and C.J.W). F.M.D. was funded by a National Health and Medical Research Council CJ Martin Biomedical Fellowship (GNT1071074). O.B.H. was funded by a Wellcome Trust PhD studentship (105377/Z/14/Z)

Treatment of intracerebral haemorrhage with tranexamic acid : A review of current evidence and ongoing trials

Peer reviewe