Impact of expanded strong opioid availability on opioid prescription patterns in patients with cancer: A population-wide cohort study in Taiwan.

Background One of the major barriers to adequate cancer pain management in Taiwan is the limited prescription options regarding strong opioids. Internationally recommended strong opioids, including oxycodone and hydromorphone, were not introduced in Taiwan until late 2014. We analysed the patterns in opioid prescription for cancer pain management, after the introduction of new opioid options. Methods All inpatient and outpatient clinical visits from January 1, 2012, to December 31, 2017, with the diagnosis of cancer and the analgesic prescriptions were collected from the database of National Health Insurance, Taiwan, and analysed. Opioids were grouped into strong opioids, weak opioids, and guideline non-recommended opioids. Findings A total of 1, 292, 905 patients with cancers were included. Approximately 50% of patients used analgesics, 50% of which were opioids; the proportions were stable during the study period. The annual cumulative opioid use per patient (defined daily dose, DDD) significantly decreased from 36•41±102•59 (Mean±SD) in 2012 to 32•42±100•99 in 2017 (p < •001). The annual cumulative strong opioid use per patient increased significantly from 17•54±89•23 in 2012 to 19•28±94•97 in 2017 (+9•90%, p < •001). In parallel, the annual cumulative weak opioids use per patient decreased from 18•64±40•81 in 2012 to 13•04±26•79 in 2017 (-30•04%, p < •001). Among extended-release strong opioids, the use of transdermal fentanyl significantly decreased after oxycodone and hydromorphone were introduced (p < •001). Interpretation Increased therapeutic options in strong opioid prescriptions led opioid prescription patterns to evolve towards international cancer pain management guidelines. In addition, increased accessibility to a wider range of different strong opioids may facilitate more efficient opioid titration and rotation - and thus decrease, not increase, the opioid usage. Funding This study was supported by Ministry of Science and Technology, Taiwan (MOST-106-2314-B-002-213 and MOST-108-2314-B-002-072-MY3), Ministry of Health and Welfare, Taiwan (MOHW109-TDU-B-211-114002), National Taiwan University Hospital, Taipei, Taiwan (NTUH-103-002314 and NTUH. 105-S2954), and National Center of Excellence for Clinical Trial & Research, National Taiwan University Hospital, Taipei, Taiwan (NCTRC201208 and NCTRC201603).

Evolution of systemic treatment for advanced hepatocellular carcinoma.

Advanced hepatocellular carcinoma (HCC) was considered an inherently refractory tumor in the chemotherapy era (1950-2000). However, systemic therapy has evolved to molecular targeted therapy and immunotherapy, and nine treatment regimens have been approved worldwide during the past 20 years. The approved regimens target tumor angiogenesis or tumor immunity, the two cancer hallmarks. Recently, the combination of atezolizumab (antiprogrammed cell death ligand 1) and bevacizumab (anti-vascular endothelial growth factor) has improved the efficacy of systemic therapy in treating advanced HCC without excessive toxicities or deterioration of quality of life. This review summarizes the major advances in systemic therapy and provides future perspectives on the next-generation systemic therapy for advanced HCC.

Moving Beyond 3+3: The Future of Clinical Trial Design.

Misgivings have been raised about the operating characteristics of the canonical 3+3 dose-escalation phase I clinical trial design. Yet, the traditional 3+3 design is still the most commonly used. Although it has been implied that adhering to this design is due to a stubborn reluctance to adopt change despite other designs performing better in hypothetical computer-generated simulation models, the continued adherence to 3+3 dose-escalation phase I strategies is more likely because these designs perform the best in the real world, pinpointing the correct dose and important side effects with an acceptable degree of precision. Beyond statistical simulations, there are little data to refute the supposed shortcomings ascribed to the 3+3 method. Even so, to address the unique nuances of gene- and immune-targeted compounds, a variety of inventive phase 1 trial designs have been suggested. Strategies for developing these therapies have launched first-in-human studies devised to acquire a breadth of patient data that far exceed the size of a typical phase I design and blur the distinction between dose selection and efficacy evaluation. Recent phase I trials of promising cancer therapies assessed objective tumor response and durability at various doses and schedules as well as incorporated multiple expansion cohorts spanning a variety of histology or biomarker-defined tumor subtypes, sometimes resulting in U.S. Food and Drug Administration approval after phase I. This article reviews recent innovations in phase I design from the perspective of multiple stakeholders and provides recommendations for future trials.

Monolithic integration of GaN-based phototransistors and light-emitting diodes.

Monolithic integration of GaN-based phototransistors and light-emitting diodes (LEDs) is reported. Starting with an LED epitaxial wafer, selective Si diffusion was performed to produce an n-p-i-n structure for the phototransistor. A traditional AlGaN bulk electron-blocking layer (EBL) can block electron injection from an emitter to a collector, thereby hindering the photocurrent amplification process. We used an LED wafer with a superlattice EBL; blocking can be removed under a bias of approximately 7 V and above. External quantum efficiencies of more than 100% and 600% at approximately 380 nm and 330 nm, respectively, were achieved at room temperature and a bias of 11 V, corresponding to responsivities of 0.31 and 1.6 A/W, respectively, significantly higher than commercially available ultraviolet (UV) detectors. Furthermore, we demonstrated an integrated operation of the device. UV light was detected using a phototransistor that sent signals to drive an integrated LED as an indicator.