Effects of the combination of atomoxetine and oxybutynin in Japanese patients with obstructive sleep apnoea: A randomized controlled crossover trial.

BACKGROUND AND OBJECTIVE: The possibility of combination therapy with atomoxetine (ATO) and oxybutynin (OXY) has been suggested for obstructive sleep apnoea (OSA). However, the effectiveness of this treatment remains uninvestigated in Japanese OSA patients. Therefore, we performed a randomized, crossover, phase II, single-centre prospective trial to examine the effects of ATO-OXY therapy in Japanese OSA patients. METHODS: In total, 17 OSA patients participated in this study. The effects of one night of 80-mg ATO plus 5-mg OXY administration were compared with those of no medication administered before sleep. The primary and secondary outcomes comprised the apnoea-hypopnoea index (AHI) and nadir SpO2 , SpO2 drop time and sleep architecture, respectively. The safety endpoints included drug side effects and adverse events. RESULTS: The values of AHI, nadir SpO2 , 3% oxygen desaturation index (ODI), 4% ODI, and SpO2 drop time of <90% did not significantly differ between patients receiving ATO-OXY administration and no medication. Sleep architecture exhibited a significant change: ATO-OXY increased sleep stage N1 (p < 0.0001) and decreased stage N2 (p = 0.03), rapid eye movement (p < 0.0001) and sleep efficiency (p = 0.02). However, the subanalysis demonstrated an obvious decrease in AHI in five responder patients. Total sleep time and basal sleep efficiency tended to be lower in the responders compared with nonresponders (p = 0.065). No patients experienced severe adverse events or side effects. CONCLUSION: Overall, ATO-OXY therapy does not reduce AHI in Japanese OSA patients, although AHI was decreased in a proportion of patients. Future studies for identifying treatment response group characteristics are warranted.

Effectiveness of Lung Ultrasound Training Utilizing a High-Fidelity Simulator.

Background: The usefulness of lung ultrasound (LUS) has been demonstrated. However, it is unclear whether diagnostic techniques using LUS are accepted by all physicians. A simple simulation-based educational program may improve the LUS skills of beginners, but it has not been fully assessed. Objective: This prospective study was conducted to assess the educational outcomes of LUS training using a high-fidelity simulator. Methods: A simulator-based program for LUS was conducted. All clerkship students at the Department of Respirology at Chiba University Hospital participated in the program from December 2022 to April 2023. The participants watched a 30 minute teaching video on demand before a hands-on session lasting for 1 hour during the first week of the clinical clerkship. The readiness of the participants to learn LUS and the usefulness of the program were assessed using questionnaires administered before and after the program. The LUS skills were assessed using simulator-based tests during Weeks 1 and 4. Data on the accuracy and time required to answer the questions were collected during the tests. Results: Forty clerkship students participated in this study. Thirty-three (82.5%) had received other ultrasound education; however, only two (5.0%) had experience with LUS. Based on the questionnaire responses, the participants perceived LUS as useful (preprogram: 4.6 vs. postprogram: 4.8; P = 0.010; a 5-point Likert scale was used [1: not useful to 5: useful]). The simulator-based tests showed comparable accuracies at Weeks 1 and 4 for pneumothorax (Week 1: 47.5% vs. Week 4: 52.5%; P = 0.623), pulmonary edema (Week 1: 100% vs. Week 4: 100%; P = 1.000), and pleural effusion (Week 1: 37.5% vs. Week 4: 40.0%; P = 0.800). The time required for scanning was the same for each question. In addition, the test results did not differ with prior learning, previous knowledge, or experience during clinical clerkships on LUS. Conclusion: A short educational program consisting of on-demand learning and hands-on sessions with a high-fidelity simulator would be effective in equipping clerkship students with basic LUS skills. However, to increase its educational effectiveness to a practical degree, the program should be improved, and more opportunities for training using simulators should be provided.

Complications Rate and a Multidimensional Analysis of Their Causes of Tube Thoracostomy: A Mixed-Methods Study.

INTRODUCTION: Tube thoracostomy (TT) complications are common in respiratory medicine. However, the prevalence of complications and risk factors is unknown, and data on countermeasures are lacking. METHODS: This was a mixed-methods retrospective observational and qualitative study. This retrospective observational study included TT performed on patients admitted to the Department of Respiratory Medicine at our University Hospital between January 1, 2019, and August 31, 2022 (n=169). The primary endpoint was the incidence of TT-related complications. We reviewed the association between complications and patient- and medical-related factors as secondary endpoints. In this qualitative study, we theorized the background of physicians' susceptibility to TT-related complications based on the grounded theory approach. RESULTS:  Complications were observed in 20 (11.8%) of the 169 procedures; however, they were unrelated to 30-day mortality. Poor activities of daily living (odds ratio 4.3, p=0.007) and regular administration of oral steroids (odds ratio 3.1, p=0.025) were identified as patient-related risk factors. Physicians undergoing training caused the most complications, and the absence of a senior physician at the procedure site (odds ratio 3.5, p=0.031) was identified as a medical risk factor. Based on this qualitative study, we developed a new model for TT complication rates consistent with the relationship between physicians' professional skills, professional identity, and work environments. CONCLUSIONS: Complications associated with TT are common. Therefore, it is necessary to implement measures similar to those identified in this study. Particularly, a supportive environment should be established for the training of physicians.

Effect of a workplace-based learning program on clerkship students' behaviors and attitudes toward evidence-based medicine practice.

In clinical clerkship (CC), medical students can practice evidence-based medicine (EBM) with their assigned patients. Although CC can be a valuable opportunity for EBM education, the impact of EBM training, including long-term behavioral changes, remains unclear. One hundred and nine fourth- and fifth-year medical students undergoing CC at a medical school in Japan attended a workplace-based learning program for EBM during CC (WB-EBM), which included the practice of the five steps of EBM. The program's effect on the students' attitudes toward EBM in CC was assessed through questionnaires. A total of 88 medical students participated in the program. Responses to the questionnaire indicated high satisfaction with the WB-EBM program. The most common theme in students' clinical problems with their assigned patients was the choice of treatment, followed by its effect. Based on the responses in the post-survey for the long-term effects of the program, the frequency of problem formulation and article reading tended to increase in the 'within six months' group comprising 18 students who participated in the WB-EBM program, compared with the control group comprising 34 students who did not. Additionally, the ability to self-assess problem formulation was significantly higher, compared with the control group. However, among 52 students who participated in the WB-EBM program more than six months later, EBM-related behavioral habits in CC and self-assessments of the five steps of EBM were not significantly different from those in the control group. The WB-EBM program was acceptable for medical students in CC. It motivated them to formulate clinical questions and enhanced their critical thinking. Moreover, the WB-EBM program can improve habits and self-evaluations about EBM. However, as its effects may not last more than six months, it may need to be repeated across departments throughout CC to change behavior in EBM practice.

The effects of simple graphical and mental visualization of lung sounds in teaching lung auscultation during clinical clerkship: A preliminary study.

INTRODUCTION: The study aimed to evaluate visualization-based training's effects on lung auscultation during clinical clerkship (CC) in the Department of Respiratory Medicine on student skills and confidence. METHODS: The study period was December 2020-November 2021. Overall, 65 students attended a lecture on lung auscultation featuring a simulator (Mr. Lung™). Among them, 35 (visualization group) received additional training wherein they were asked to mentally visualize lung sounds using a graphical visualized lung sounds diagram as an example. All students answered questions on their self-efficacy regarding lung auscultation before and after four weeks of CC. They also took a lung auscultation test with the simulator at the beginning of CC (pre-test) and on the last day of the third week (post-test) (maximum score: 25). We compared the answers in the questionnaire and the test scores between the visualization group and students who only attended the lecture (control group, n = 30). The Wilcoxon signed-rank test and analysis of covariance were used to compare the answers to the questionnaire about confidence in lung auscultation and the scores of the lung auscultation tests before and after the training. RESULTS: Confidence in auscultation of lung sounds significantly increased in both groups (five-point Likert scale, visualization group: pre-questionnaire median 1 [Interquartile range 1] to post-questionnaire 3 [1], p<0.001; control group: 2 [1] to 3 [1], p<0.001) and was significantly higher in the visualization than in the control group. Test scores increased in both groups (visualization group: pre-test 11 [2] to post-test 15 [4], p<0.001; control group: 11 [5] to 14 [4], p<0.001). However, there were no differences between both groups' pre and post-tests scores (p = 0.623). CONCLUSION: Visualizing lung sounds may increase medical students' confidence in their lung auscultation skills; this may reduce their resistance to lung auscultation and encourage the repeated auscultation necessary to further improve their long-term auscultation abilities.

A case of pseudomyxoma peritonei successfully treated with trifluridine/tipiracil (TAS-102) and bevacizumab after palliative debulking surgery.

Pseudomyxoma peritonei is a rare disease with a reported prevalence of about 1-3 per million people annually. Cytoreductive surgery and perioperative hyperthermic intraperitoneal chemotherapy are considered as treatment options improving disease control or long-term survival. However, for patients with incomplete cytoreduction or debulking surgery, outcomes are significantly poorer compared with patients who have obtained complete or optimal cytoreduction. In cases of high-grade pseudomyxoma peritonei that are considered inoperable and/or unresectable, combination chemotherapy regimen with a neo-angiogenesis inhibitor such as bevacizumab is recommended. In this report, a 62-year-old Japanese man presented with abdominal distention. Examination of ascites demonstrated a jelly-like consistency and peritoneal pseudomyxoma was suspected. To relieve progressive symptoms, palliative debulking surgery with total colectomy was performed. Postoperative pathology confirmed high-grade appendiceal mucinous neoplasm with high-grade pseudomyxoma peritonei. In our case, combination chemotherapy with trifluridine/tipiracil (TAS-102) and bevacizumab was initiated after palliative debulking surgery. As a result, carcinoembryonic antigen level was kept stable and the volume of ascites remained almost the same as at the beginning of treatment for more than 2 years. In conclusion, combination chemotherapy comprising TAS-102 and bevacizumab in patients with palliative debulking could be a useful option for patients with high-grade mucinous appendiceal neoplasm and high-grade pseudomyxoma peritonei.

Pembrolizumab for Previously Untreated Patients with Advanced Non-small-cell Lung Cancer and Preexisting Interstitial Lung Disease.

Objective Pembrolizumab has benefited patients with advanced non-small-cell lung cancer (NSCLC) with a programmed death-ligand (PD-L) 1 high expression, but little information is available regarding its safety for patients with interstitial lung disease (ILD). The aim of this study was to assess the efficacy and tolerability of pembrolizumab for patients with advanced NSCLC and preexisting ILD. Methods We retrospectively reviewed the medical records of five patients with advanced NSCLC and preexisting ILD who received pembrolizumab monotherapy in a first-line setting. Patients All patients had mild ILD and pulmonary emphysema with a forced vital capacity within the normal range. Pembrolizumab was administered at a dose of 200 mg/body on day 1 every 3 weeks. Results The overall response rate was 60%. Four patients developed pembrolizumab-induced lung injury, which was improved in all cases by corticosteroid therapy. One patient received pembrolizumab for two years, did not experience lung injury and achieved a complete response. Conclusion Pembrolizumab has a high risk of inducing lung injury in patients with preexisting ILD, although it may be very effective in NSCLC patients with a high PD-L1 expression, even concurrent with preexisting ILD. Further large-scale studies are needed to determine risk factors of pembrolizumab-induced lung injury in such patients.

Pemetrexed Plus Platinum for Patients With Advanced Non-small Cell Lung Cancer and Interstitial Lung Disease.

BACKGROUND/AIM: Pemetrexed plus platinum followed by pemetrexed maintenance has been one of the standard first-line treatments in advanced nonsquamous non-small cell lung cancer (NSCLC), but little is known regarding its safety and efficacy for patients with interstitial lung disease (ILD). PATIENTS AND METHODS: The medical records of 24 patients with advanced nonsquamous NSCLC and preexisting ILD who received pemetrexed and platinum doublet therapy with and without pemetrexed maintenance in the first-line setting between December 2009 and June 2016, were retrospectively reviewed. RESULTS: The median progression-free survival time was 4.7 months, and the median overall survival time was 9.5 months. Of the 24 patients analyzed, six received pemetrexed maintenance. Acute exacerbation of ILD (AE-ILD) occurred in five (20.8 %) of 24 patients, including two fatal cases. CONCLUSION: The treatment with pemetrexed plus platinum has a high risk of AE-ILD in patients with advanced nonsquamous NSCLC and preexisting ILD.

Pembrolizumab-induced interstitial lung disease following thoracic surgery in a patient with non-small cell lung cancer.

The safety of treatment with immune-checkpoint inhibitors prior to thoracic surgery in patients with non-small cell lung cancer (NSCLC) remains unclear. Here, we describe the case of a 62-year-old woman with NSCLC with programmed death ligand 1 expression on 85% of tumor cells. The patient was initially considered to have unresectable stage IIIB disease and received pembrolizumab monotherapy. After 12 cycles of pembrolizumab, the primary tumor was reduced, but a small lung nodule in another lobe was unchanged. Based on the course of image findings, the nodule was considered to be an old inflammatory change. The clinical stage was changed to stage IB and partial resection was performed. Three days after thoracic surgery, the patient began to complain of coughing and shortness of breath. A CT of the chest revealed ground-glass opacity in the bilateral lung fields, suggesting interstitial lung disease (ILD) associated with pembrolizumab. Corticosteroid therapy was started and a chest X-ray showed a reduction in the opacity with improved oxygenation. This is the first case of immune-checkpoint inhibitor-related ILD triggered by thoracic surgery following long-term immune-checkpoint therapy.