Assessing the economics of biologic and small molecule therapies for the treatment of moderate to severe ulcerative colitis in Japan: a cost per responder analysis of upadacitinib.

AIM: Patients with moderately to severely active ulcerative colitis have an increasing number of advanced therapy options including several biologics and Janus kinase inhibitors. Though data on efficacy and safety of these advanced therapies are available, less is known about the potential economic implications of their utilization in Japan. We evaluated the relative value of these advanced therapies in Japan using a locally developed cost per responder model. METHODS: A model was developed using relevant clinical endpoints and treatment costs to calculate cost per responder of all advanced therapies used for moderately to severely active ulcerative colitis treatment in Japan. Cost per responder was assessed in biologic-naïve and biologic-exposed populations, respectively. The model incorporated induction and maintenance therapy pathways as patients progressed through based on efficacy rates (clinical response, clinical remission and endoscopic improvement). Total costs for induction and maintenance included: drug acquisition, drug administration and serious adverse event management (as necessary) for responders, with additional rescue treatment cost only for non-responders. RESULTS: Upadacitinib showed lower cost per clinical response and cost per clinical remission across both biologic-naïve and biologic-exposed populations with only one exemption in cost per clinical remission in biologic-naïve population. In addition, upadacitinib demonstrated lower cost per endoscopic improvement in both populations. Janus kinase inhibitors outperformed with lower cost per responder than other mediations across all outcomes and patient populations with the exception of tofacitinib for clinical remission in biologic-exposed UC population. LIMITATIONS: Comparative data used in this analysis have been derived from network meta-analysis, not from direct comparison. CONCLUSIONS: The results of this cost per responder analysis suggest upadacitinib is a cost-effective option for the first- and second-line treatment of moderately to severely active ulcerative colitis in Japan.

Order transfer in a hybrid Raman-laser-optomechanical resonator.

Order is one of the most important concepts to interpret various phenomena such as the emergence of turbulence and the life-evolution process. The generation of laser can also be treated as an ordering process in which the interaction between the laser beam and the gain medium leads to the correlation between photons in the output optical field. Here, we demonstrate experimentally in a hybrid Raman-laser-optomechanical system that an ordered Raman laser can be generated from an entropy-absorption process by a chaotic optomechanical resonator. When the optomechanical resonator is chaotic or disordered enough, the Raman-laser field is in an ordered lasing mode. This can be interpreted by the entropy transfer from the Raman-laser mode to the chaotic motion mediated by optomechanics. Different order parameters, such as the box-counting dimension, the maximal Lyapunov exponent, and the Kolmogorov entropy, are introduced to quantitatively analyze this entropy transfer process, by which we can observe the order transfer between the Raman-laser mode and the optomechanical resonator. Our study presents a new mechanism of laser generation and opens up new dimensions of research such as the modulation of laser by optomechanics.

Association between meat intake and mortality due to all-cause and major causes of death in a Japanese population.

PURPOSE: We examined the association between meat intake and mortality due to all-cause and major causes of death using a population-based cohort study in Japan. METHODS: 87,507 Japanese aged between 45 and 74 years old at 5-year follow-up study were followed for 14.0 years on average. Associations between meat intake and mortality risk were assessed using a Cox proportional hazards model. RESULTS: A heavy intake of total meat was associated with a higher risk of all-cause mortality relative to the lowest quartile intake in men (Q4: HR,1.18; 95%CIs, 1.06-1.31). A higher intake of total meat was associated with a lower risk of stroke mortality in women (Q2: HR, 0.70; 95%CIs, 0.51-0.94, Q3: HR, 0.68; 95%CIs, 0.50-0.95, Q4: HR, 0.66; 95%CIs, 0.44-0.99). A heavy intake of red meat was also associated with all-cause mortality (Q4: HR, 1.13; 95%CIs, 1.02-1.26) and heart disease mortality (Q4: HR, 1.51; 95%CIs, 1.11-2.06) in men but not in women. Heavy intake of chicken was inversely associated with cancer mortality in men. CONCLUSIONS: Heavy intakes of total and red meat were associated with an increase in all-cause and heart disease mortality in men, while total meat intake was associated with a lower risk of stroke mortality in women.

Harmine combined with paclitaxel inhibits tumor proliferation and induces apoptosis through down-regulation of cyclooxygenase-2 expression in gastric cancer.

Cyclooxygenase-2 (COX-2) serves an important role in the carcinogenesis and progression of gastric cancer. Harmine (HM) and paclitaxel (PTX) are reported as promising drug candidates for cancer therapy, but whether a synergistic anti-tumor effect of HM combined with PTX exists in human gastric cancer remains unknown. The present study evaluated the effects of HM and/or PTX on cell proliferation and apoptosis in a gastric cancer cell line, SGC-7901. HM and PTX inhibited cell proliferation in a dose-dependent manner. Both HM and PTX alone induced apoptosis in gastric cancer cells. The combination of HM and PTX exerted synergistic effects on proliferation inhibition and apoptosis induction in SGC-7901 cells, with down-regulation of COX-2, PCNA and Bcl-2 and up-regulation of Bax expression. The results indicated that combination chemotherapy using HM with PTX exerts an anti-tumor effect for treating gastric cancer. The combination of the two drugs inhibits gastric cancer development more effectively than each drug alone through down-regulation of COX-2 expression.

Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase-2 expression.

Cyclooxygenase-2 (COX-2) has a critical role in the invasiveness and metastasis of gastric cancer. In addition, paclitaxel (PTX) and harmine (HM) were reported to be potential therapeutic drug candidates for cancer therapy; however, the synergistic antitumor effect of PTX and HM combined treatment on the human gastric cancer cells remains to be elucidated. The aim of the present study was to evaluate the effects of PTX and/or HM on the cell migration and invasion in two human gastric cancer cell lines, SGC-7901 and MKN-45. MTT assay was used to detect the growth inhibition induced by PTX and HM. The Transwell assay was employed to assess the effects of PTX and HM on the cell migration and invasion. The expression levels of COX-2 and matrix metalloproteinase-9 (MMP-9) were analyzed by western blot analysis. The results demonstrated that PTX and HM inhibited cell proliferation in a dose-dependent manner. Individually PTX and HM were able to inhibit the migration and invasion of two human gastric cancer cells; however, the combination of PTX and HM exerted synergistic effects on migration and invasion inhibition, with downregulation of COX-2 and matrix metalloproteinase (MMP)-9. In conclusion, the results of the present study indicated that combination chemotherapy using PTX with HM exerted an antitumor effect, which may be implicated for the treatment of gastric cancer. Of note, the combination of the two drugs inhibited migration and invasion more effectively compared with each drug alone, the mechanism of which proceeded via the downregulation of COX-2 expression.