The effects of inflammation on collagenase and gelatinase were studied in dog gingiva. Inflammation was induced by the placement of cervical ligatures. Collagenase activity was measured using soluble [14C]‐acetylated collagen with high specific activity as substrate and separating the reaction products by 50% dioxane (Terato et al. 1976). Two forms of collagenase, a soluble enzyme free from the substrate and an insoluble enzyme bound to the substrate, were extracted by neutral salt solution and by sequential sonication in low and high salt buffers, respectively. Treatment with a high concentration of trypsin was necessary for detection of collagenase activities in both extracts. The collagenase activities in the neutral salt extract and the first sonic extract were significantly higher in inflamed gingiva after 1 week of plaque formation than in healthy gingiva, but that in the second sonic extract showed no significant increase. After 3 weeks of plaque formation, the activities in neutral salt extract and the first sonic extract of inflamed gingiva similarly showed significant increases relative to controls. On the other hand, gelatinase activity did not vary significantly with the induction of inflammation.
Aim
Previous studies indicate that mirtazapine is unique in its quick responsiveness compared to other antidepressants. Although some other studies have evaluated its cost‐effectiveness, they have not considered its early stage remission rate. The aim of this study was to address this research gap by using precise clinical data to evaluate the cost‐effectiveness of mirtazapine in Japan.
Methods
We developed a Markov model to reflect the week‐by‐week transition probabilities. The Markov cycle was set as 1 week. While our clinical parameters were obtained largely from existing meta‐analyses, cost data were derived from government reports. Cost‐effectiveness was evaluated by incremental cost‐effectiveness ratios (ICERs) per quality‐adjusted life year estimated based on the probability sensitivity analyses. The ICERs were estimated at 2, 8, 26, and 52 weeks.
Results
In severe depression, the ICERs ranged between JPY 872 153 and 1 772 723. The probability of mirtazapine being cost‐effective ranged from 0.75 to 0.99 when the ICER threshold was JPY 5 000 000. In moderate depression, the ICERs ranged between JPY 2 356 499 and 4 770 145. The probability of mirtazapine being cost‐effective ranged from 0.55 to 0.83 when the ICER threshold was JPY 5 000 000.
Conclusion
When considering the early stage efficacy of mirtazapine, it appeared to be cost‐effective compared to selective serotonin reuptake inhibitors, especially for severe depression and in the early stage treatment in the Japanese setting. However, our study has some limitations. First, mirtazapine is compared with batched selective serotonin reuptake inhibitors rather than individual ones. Second, we did not consider antidepressant combination therapy as treatment options.
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