Rationale and design of a multicenter, double-blinded, randomized, placebo-controlled trial to investigate the effects of naldemedine on opioid-induced constipation for patients with cancer pain: A study protocol.

Background: It is unclear which laxatives are appropriate to prevent opioid-induced constipation (OIC). This study will evaluate whether prophylactic use of naldemedine prevents OIC in patients with cancer who start opioid administration. Methods: This study is a multicenter, double-blinded, randomized, placebo-controlled trial. Patients who meet the eligibility criteria and give consent will be randomly assigned to the naldemedine or placebo group. Both groups will take each drug once a day after breakfast for 14 days. Results: The primary endpoint is the proportion of patients with a Bowel Function Index of less than 28.8 on Day 14. The secondary endpoints include assessment scales of the impact of constipation on comprehensive quality of life. Conclusions: This is the first study proposed to assess the superiority of naldemedine over placebo in the prevention of OIC. If naldemedine is found to be effective in reducing OIC compared with the placebo, it will be regarded as a new standard for OIC prophylaxis at opioid initiation. Trial registration: jRCT identifier: jRCTs031200397. Registered March 5, 2021, https://rctportal.niph.go.jp/en/detail?trial_id=jRCTs031200397.

Morphological changes in the optic disc after vitrectomy and fluid-air exchange.

BACKGROUND: Although many investigators have previously reported various ocular complications induced by vitrectomy, little is known about post-operative morphological changes in the optic disc. The purpose of this study is to evaluate the effect of vitrectomy and fluid-air (F-A) exchange on the post-operative morphology of the optic disc. METHODS: We examined 31 eyes that had undergone vitrectomy for macular holes (22 eyes) or epiretinal membranes (9 eyes). Only the patients with macular holes were treated by fluid-air exchange. Morphological changes in the optic disc were evaluated using the Heidelberg Retina Tomograph. RESULTS: C/D area ratios significantly decreased for 6 months post-operatively. The rim volumes significantly increased for 1 month following surgery. Cup volumes significantly decreased at 3 months after surgery. No significant change of mean cup depth was observed post-operatively. The eyes that had not been subjected to F-A exchange showed no significant morphological change following surgery. In contrast, the eyes that had undergone F-A exchange showed significant decrease in C/D area ratio and cup volume and an increase in rim volume and mean cup depth for considerable periods following surgery. Any of the patients showed no post-operative visual field loss. CONCLUSION: Whereas no visual field loss is observed, vitrectomy with F-A exchange induces morphological changes in the optic disc for significant periods following surgery.