Efficacy and safety of once-daily single-inhaler triple therapy for mild-to-moderate chronic obstructive pulmonary disease: a study protocol for a randomised and interventional study.

INTRODUCTION: Bronchodilators, including long-acting muscarinic antagonists (LAMA) and long-acting beta 2 agonists (LABA), are the main treatments for chronic obstructive pulmonary disease (COPD). The efficacy of triple therapy (inhaled corticosteroids/LAMA/LABA) has also been reported. However, the effect of triple therapy on patients with mild-to-moderate COPD has not yet been clarified. This study aims to investigate the safety and efficacy of triple therapy, compared with LAMA/LABA combination therapy, for lung function and health-related quality of life in patients with mild-to-moderate COPD and identify baseline characteristics and biomarkers to predict responders and non-responders to triple therapy. METHODS AND ANALYSIS: This is a multicentre, prospective, open-label, randomised, parallel-group study. Mild-to-moderate patients with COPD will be randomised to receive fluticasone furoate/umeclidinium/vilanterol or umeclidinium/vilanterol for 24 weeks. A total of 668 patients will be enrolled from March 2022 to September 2023 from 38 sites in Japan. The primary endpoint is the change in the trough forced expiration volume in 1 s after 12 weeks of treatment. Secondary endpoints are responder rates based on the COPD assessment test score and the St. George's Respiratory Questionnaire total score after 24 weeks of treatment. The safety endpoint is the occurrence of any adverse events. We will also investigate safety in terms of changes in microbial colonisation in sputum and antimycobacterium avium complex antibodies. ETHICS AND DISSEMINATION: The study protocol and informed consent documents were approved by the Saga University Clinical Research Review Board (approval number: CRB7180010). Written informed consent will be obtained from all patients. Recruitment of the patients began in March 2022. The results will be disseminated through scientific peer-reviewed publications and domestic and international medical conferences. TRIAL REGISTRATION NUMBERS: UMIN000046812 and jRCTs031190008.

Risk factors for peristomal skin disorders associated with temporary ileostomy construction.

PURPOSE: Skin disorders are the most common stoma-related complications after temporary diverting loop ileostomy with proctectomy. The aim of the present study was to investigate risk factors for skin disorders associated with temporary ileostomy construction. METHODS: A total of 185 consecutive patients who underwent curative proctectomy with temporary diverting loop ileostomy for rectal malignancies at a single comprehensive cancer center between 2013 and 2018 were collected and analyzed. RESULTS: The most frequent stoma-related complications were skin disorders (n = 62, 33.5%), followed by mucocutaneous separation (n = 38, 20.5%) and high-output stoma (n = 34, 18.4%). Patients with skin disorders had a higher median body mass index (BMI; 22.4 vs. 21.3 kg/m2, P = 0.002) and lower stoma height (16 vs. 20 mm, P < 0.001) than those without skin disorders. According to a multivariable logistic regression analysis, independent predictors of skin disorders included overweight (median BMI ≥ 25 kg/m2 [odds ratio = 3.6, 95% confidence interval: 1.5-8.6], P = 0.004) and lower stomal height (median stoma height < 20 mm [odds ratio = 3.2, 95% confidence interval: 1.6-6.3], P < 0.001). CONCLUSION: Overweight and lower stoma height are correlated with the presence of skin disorders. Construction of a well-elevated stoma can reduce skin disorders associated with temporary ileostomy construction.

Surgical Strategy for Rectovaginal Fistula After Colorectal Anastomosis at a High-volume Cancer Center According to Image Type and Colonoscopy Findings.

BACKGROUND/AIM: The reported incidence of rectovaginal fistula is very low. Although some case reports have described surgical procedures, no systematic approach to the treatment of rectovaginal fistula according to diagnostic image and colonoscopy findings has been proposed. We present a comprehensive surgical strategy for rectovaginal fistula after colorectal anastomosis according to diagnostic image and colonoscopy findings. PATIENTS AND METHODS: This retrospective study included 11 patients who developed rectovaginal fistula after colorectal anastomosis. Rectovaginal fistula was classified into 4 types according to contrast enema images and colonoscopy findings, i.e., "Alone type", "Dead space type", "Anastomotic stricture type", and "Dead space and Anastomotic stricture type". The surgical strategies were "Diversion (Stoma)", "Percutaneous drainage", "Anastomotic stricture type", "Endoscopic balloon dilation", "Curettage of foreign bodies", "Simple full-thickness closure", "Split-thickness closure", "Pedicled flaps packing", and "Reanastomosis". The surgical strategy appropriate for each rectovaginal fistula type was investigated. RESULTS: Among "Alone type" cases, 5 (71.4%) healed with "only Diversion (Stoma)". "Alone type" cases (n=11) and all other cases (n=4) healed with "only Diversion (Stoma)" (n=5) or any other method (n=6) (p=0.022). CONCLUSION: For treatment of rectovaginal fistula after colorectal anastomosis, less invasive treatment approaches should be attempted first.

Screening for new antidepressant leads of multiple activities by support vector machines.

Virtual screening was carried out against 21 biological targets related to depression by support vector machine classification using the same atom-type descriptors. The models were effective as 0.2-0.8 of theoretical enrichments of the external test data sets could be achieved, depending on the target. The set of predicted active molecules had large diversity and contained examples with high dissimilarity to the compounds of training sets. Filtering the database of known antidepressants by all 21 models it was found that on average compounds were classified active for 2.3 targets.

Virtual screening models for finding novel antidepressants.

Virtual screening was carried out against various biological targets related to depression by support vector machine classification using the atom-type descriptors. The models were effective as over 75 and 95% of the molecules in external test datasets could be correctly classified, depending on target. Antidepressant compounds had predicted activity against 2.3 targets, on average. An introduction is given to virtual screening and the results of classification experiments are presented.