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A significant percentage of patients have coronary artery disease that is too advanced or diffuse for percutaneous or surgical intervention. Therapeutic angiogenesis is a treatment modality to induce vessel formation that is being developed for patients with advanced coronary disease not amenable to currently available interventions. A number of approaches to induce coronary collateralization are being developed. These include gene, protein, cellular and miRNA modalities, each of which have advantages and disadvantages. At this time, no modality has emerged as the single clear choice, and combination therapies may provide synergistic benefits. However, there have been a number of recent studies advancing our knowledge as to how we can refine procollateralizing treatments. In this article, we will examine some recent successes and future obstacles in the effort to bring therapeutic angiogenesis to patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "False Memory Syndrome," by J. Boakes in the 1995 issue.

Objective: To investigate the incidence of male sexual dysfunction (SD) including erectile dysfunction (ErD) and ejaculatory dysfunction (EjD) after minimally invasive rectal cancer surgery., Background: Male SD significantly affects post-rectal cancer surgery quality of life (QOL). Current assessments using the International Index of Erectile Function-5 are unsuitable for patients with reduced postoperative sexual activity, because it assumes sexual intercourse. This study addresses this gap using the Erection Hardness Score (EHS) and custom ejaculatory questionnaires., Methods: This prospective multicenter open-label phase II trial enrolled 399 patients who underwent laparoscopic (Lap), robotic (Ro), or transanal (Ta) rectal cancer surgery. EHS and custom ejaculatory questionnaires assessed ErD, EjD, and potency impairment at 3, 6, and 12 months postoperatively. The rates were assessed in the full analysis set and compared between the Lap and Ro groups after propensity score matching., Results: At 12 months, the overall incidences of ErD and EjD were 34.7% and 29.8%, respectively. The Ro group showed a significantly lower EjD rate (25.0%) than the Lap group (40.9%), with no significant difference in ErD. Potency impairment was lower in the Ro group at 6 months (32.7% vs. 22.3%) and 12 months (29.0% vs. 17.8%) postoperatively. The Ta group showed relatively high ErD and EjD at 3 months, with some recovery at 12 months., Conclusions: Minimally invasive rectal cancer surgery commonly results in ErD, EjD, and potency impairment. Robotic surgery provides lower EjD rates and less potency impairment. Comprehensive sexual function assessments are essential to inform patients and improve QOL outcomes., Competing Interests: Conflicts of Interest and source of funding: The authors declare no conflicts of interest directly relevant to the content of this article. The authors declare that no funding was received in support of this study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Opioid-induced constipation is the most frequent and non-self-limiting adverse effect of opioid analgesia, reducing adherence and interfering with pain relief. This clinical trial aimed to clarify the preventive effect of naldemedine versus placebo for constipation in patients with cancer starting regularly dosed strong opioids therapy., Methods: This multicenter, double-blinded, randomized, placebo-controlled, confirmatory trial was conducted between July 2021 and May 2023 at four academic hospitals in Japan (ClinicalTrials.gov identifier: jRCTs031200397). Patients with cancer starting a first-time regularly dosed strong opioid for cancer pain and age 20+ years were included. Eligible patients were randomly assigned to the naldemedine (Symproic 0.2 mg) or placebo group in a 1:1 ratio for 14 days with protocol treatment. The primary end point was the proportion of patients with a Bowel Function Index (BFI) of <28.8 on day 14. The secondary end points included frequency of spontaneous bowel movements (SBM), quality of life (QOL), and frequency of opioid-induced nausea and vomiting (OINV)., Results: Of the 103 patients assessed for eligibility, 99 received either naldemedine (n = 49) or placebo (n = 50). A BFI of <28.8 on day 14 was significantly more likely to occur in the naldemedine group (64.6%; 95% CI, 51.1 to 78.1) versus placebo (17.0%; 95% CI, 6.3 to 27.8), and the difference between groups was 47.6% (95% CI, 30.3 to 64.8; P < .0001). The frequency of SBM, QOL, and the severity of OINV were nominally significant in the naldemedine group than in the control group., Conclusion: Naldemedine prevented constipation and improved constipation-related QOL, with possible preventive effect on OINV in patients with cancer starting regularly dosed opioids therapy.

Background: This study sought to investigate the symptoms and prognoses of patients with breast cancer and malignant wounds in the palliative care unit setting., Methods: This study was a sub-group analysis of a multicenter, prospective, observational study. Patients admitted to 23 palliative care units in Japan between January and December 2017 were enrolled. Data of patients with breast cancer were extracted. We compared demographic characteristics, symptoms, and prognoses by breast cancer malignant wound status. The primary outcome was overall survival. Secondary outcomes included Palliative Prognostic Index (PPI) score, malignant wound characteristics, and symptom burden., Results: Of 1896 patients, 131 (6.9%) had breast cancer. In this cohort, 44 (33.6%) patients had malignant wounds. Most malignant wounds (88%) were on the back and chest. Malignant wounds were associated with skin redness, erosion, necrosis, or fistula. Symptoms included bleeding, exudate, odor, and pain. Twenty-eight patients (63.6%) needed dressing changes and 14 (31.8%) patients experienced bleeding. None died due to bleeding. In the malignant wounds group, 32 (72.8%) patients had used an opioid dose equivalent to 38 mg of oral morphine daily, compared to 25 mg by 57 (65.5%) patients in the non-malignant wounds group ( P = .26). Median PPI scores at hospital admission were 4.5 vs 6.5 ( P = .08). Median survival was 23 vs 21 days ( P = .48)., Conclusions: Patients with malignant wounds had a distinct symptom burden profile and tended to use a higher dose of opioids. The effect of malignant wounds on survival was unclear., Competing Interests: Declaration of Competing InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Although handheld ultrasound devices (HUDs) are commonplace, their ability to diagnose fecal retention (FR) remains unclear. This prospective observational study examined HUDs' usefulness in diagnosing FR in patients with constipation in a palliative care setting. Between 10 December 2020 and 30 June 2022, we compared rectal ultrasonographic findings obtained using HUDs with clinical manifestations in 64 males and 70 females (48%, 52%, 68 ± 11 years old) with constipation who had undergone computed tomography (CT). FR was diagnosed using a HUD and compared with CT and digital rectal examination (DRE) results. In total, 42 (31%), 42 (31%), and 41 (31%) patients were diagnosed using HUDs, CT, and DRE, respectively. Thirty-nine (93%) patients in the CT group were also diagnosed with FR using HUDs. A total of 89 of 92 patients with a negative CT diagnosis also had a negative HUD diagnosis. Among the 41 patients in the DRE group, 37 were also diagnosed with FR using HUDs. Among 93 patients with a negative DRE diagnosis, 86 had a negative HUD diagnosis. The sensitivity, specificity, positive predictive value, and negative predictive value of HUDs for CT were 93%, 97%, 93%, and 97%, respectively. Those of HUDs for DRE were 88%, 94%, 86%, and 95%, respectively. The concordance rates for FR diagnosis were 128/134 for CT and HUDs and 123/134 for DRE and HUDs. HUD was useful for diagnosing FR in this setting. HUDs could provide valuable support for appropriate treatment selection. Developing a constipation treatment algorithm based on rectal ultrasonographic findings is warranted in the future.

Purpose: In this study, we aimed to evaluate the safety and effectiveness of naldemedine for treating opioid-induced constipation (OIC) in patients with advanced cancer, who are receiving palliative care, and particularly explored its early effects., Methods: Palliative care teams and inpatient palliative care units across 14 institutions in Japan were included in this multicenter, prospective, observational study. Patients who were newly prescribed a daily oral dose of 0.2 mg naldemedine were enrolled. The spontaneous bowel movement (SBM) within 24 h after the first dose of naldemedine was considered the primary outcome, whereas, the secondary outcomes included weekly changes in SBM frequency and adverse events., Results: A total of 204 patients were enrolled and 184 completed the 7-day study. The average age of the participants (103 males, 101 females) was 63 ± 14 years. The primary cancer was detected in the lungs (23.5%), gastrointestinal tract (13.7%), and urological organs (9.3%). A considerable proportion of patients (34.8%) had ECOG performance status of 3-4. Most patients were undergoing active cancer treatment, however, 40.7% of the patients were receiving the best supportive care. Within 24 h of the first naldemedine dose, 146 patients (71.6%, 95% CI: 65.4-77.8%) experienced SBMs. The weekly SBM counts increased in 62.7% of the participants. The major adverse events included diarrhea and abdominal pain, detected in 17.6% and 5.4% of the patients, respectively. However, no serious adverse events were observed., Conclusion: Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings., Trial Registration Number: UMIN000031381, registered 20/02/2018., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We aimed to assess the prevalence of hazardous drinking and potential alcohol dependence among Japanese primary care patients, and their readiness to change and awareness of others' concerns., Methods: From July to August 2023, we conducted a multi-site cross-sectional study as a screening survey for participants in a cluster randomized controlled trial. The trial included outpatients aged 20-74 from primary care clinics. Using the Alcohol Use Disorders Identification Test (AUDIT) alongside a self-administered questionnaire, we evaluated the prevalence of hazardous drinking and suspected alcohol dependence, patients' readiness to change, and their awareness of others' concerns., Results: Among the 1388 participants from 18 clinics, 22% (95% confidence interval (CI): 20% to 24%) were identified as engaging in hazardous drinking or suspected of being alcohol dependent. As the AUDIT scores increased, so did their readiness to change. However, only 22% (95%CI: 16% to 28%) of those with scores ranging from 8 to 14 reported that others, including physicians, had expressed concerns about their drinking during the past year. For those with scores of 15 or higher, the figure was 74%., Conclusions: This study underscores the need for universal or high-risk alcohol screening and brief intervention in Japanese primary care settings. Trial registry UMIN-CTR (https://www.umin.ac.jp/ctr/) (UMIN000051388)., Competing Interests: Declaration of competing interest RS and HN were employees of CureApp, Inc. during the conduct of the study. RS reports grants from Osake-no-Kagaku Foundation, grants from The Mental Health Okamoto Memorial Foundation, grants from Kobayashi Magobe Memorial Medical Foundation, personal fees from Otsuka Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Sumitomo Pharma Co., Ltd. outside the submitted work; In addition, RS has a patent JP2022049590A, US20220084673A1 pending, a patent JP2022178215A pending, a patent JP2022070086 pending, and a patent JP2023074128A pending. TAF reports personal fees from Boehringer-Ingelheim, Daiichi Sankyo, DT Axis, Kyoto University Original, Shionogi, SONY and UpToDate, and a grant from DT Axis and Shionogi, outside the submitted work; In addition, TAF has patents 2020–548,587 and 2022–082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. YH and HY report personal fees from Otsuka Pharmaceutical and Cure App Inc. outside the submitted work. SM has received a research grant from Asahi Quality & Innovations, Ltd. and has received speaker's honoraria from EA Pharma, Otsuka Pharmaceutical, Yoshitomi Yakuhin, Eisai, Nippon Shinyaku, Otsuka Pharmaceutical and MSD, and personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work within the past three years. YT reports personal fees from Otsuka Pharmaceutical Co., MSD K.K. TY reports personal fees from Otsuka Pharmaceutical, Cure App Inc., and Nippon Shinyaku Co., Ltd. outside the submitted work. KN received personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work. Other authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To compare the outcomes of therapy using recombinant human fibroblast growth factor (rhFGF)-2 combined with autologous bone grafting (ABG) therapy with those of rhFGF-2 alone and ABG alone in the treatment of periodontal intraosseous defects., Methods: Periodontal intraosseous defects were randomized to receive rhFGF-2 therapy + ABG, rhFGF-2 therapy alone, or ABG alone. Periodontal examination and periapical radiography were performed preoperatively and at 3, 6, and 12 months postoperatively., Results: At the 12 months follow-up, all three groups showed significant improvement in the clinical attachment level (CAL): 5.6 ± 1.6, 5.8 ± 1.7, and 5.2 ± 1.6 mm in the rhFGF-2 + ABG, rhFGF-2 alone, and ABG alone groups, respectively, with no significant inter-group differences (p < .05). rhFGF-2 therapy (alone or in combination) resulted in greater bone defect filling (BDF) (2.3 ± 1.2 mm and 2.6 ± 1.9 mm, respectively) than ABG therapy alone (1.2 ± 1.2 mm). Gingival recession was lesser in the ABG alone (1.2 ± 1.1 mm) and rhFGF-2 + ABG groups (1.4 ± 0.8 mm) than in the rhFGF-2 alone group (2.2 ± 1.2 mm)., Conclusion: The results of this study showed that at 12 months postoperatively, all treatments resulted in statistically significant clinical improvements compared to the baseline. From these results, it can be concluded that rhFGF-2 promotes hard tissue regeneration in intraosseous defects., (© 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Objectives: Patients with malignant wounds suffer from physical and psychological symptom burden. Despite psychological support being required, the impact of malignant wounds on patients' psychological distress is poorly investigated. We evaluated psychological distress associated with malignant wounds for patients at their end of life., Methods: This study used the secondary analysis of the results of a large prospective cohort study, which investigated the dying process among patients with advanced cancer in 23 palliative care units in Japan. The primary outcome of this study was the prevalence of moderate to severe psychological symptom burden, evaluated by the Integrated Palliative Care Outcome Scale (IPOS)-feeling at peace scores of 2-4. In addition, the factors affecting psychological symptoms were investigated. The quality of death was also evaluated upon death using the Good Death Scale score., Results: Out of the total 1896 patients, 156 had malignant wounds (8.2%). Malignant wounds were more common in female and young people. The breast, head, and neck were the most prevalent primary sites. More patients with malignant wounds had IPOS-feeling at peace scores of 2-4 than patients without malignant wounds (41.0% vs. 31.3%, p  = 0.024). Furthermore, psychological distress was associated with moderate to severe IPOS-pain and the frequency of dressing changes. The presence of malignant wounds did not affect the quality of death., Significance of Results: This study showed increased psychological distress due to malignant wounds. Patients with malignant wounds require psychological support in addition to the treatment of physical symptoms for maintaining their quality of life.

Purpose: This study aimed to determine factors associated with multimodal care practices for cancer cachexia among registered dietitians (RDs) working in cancer care., Methods: A secondary analysis was performed using RDs' data. Data on knowledge, skills, and confidence in multimodal care were obtained. Nine items regarding multimodal care practices were evaluated. Subjects were divided into two groups based on their answers associated with the nine items. Comparisons were obtained using the Mann-Whitney U test or chi-squared test. Multiple regression analysis was performed to identify the critical factors involved in practicing multimodal care by determining the variables with significant differences between the two groups., Results: Two hundred thirty-two RDs were included in this study. Significant differences were observed in their primary area of practice (p = 0.023), the number of clinical guidelines used (p < 0.001), the number of items used in cancer cachexia assessment (p = 0.002), the number of symptoms used in cancer cachexia assessment (p = 0.039), training for cancer cachexia (p < 0.001), knowledge of cancer cachexia (p < 0.001), and confidence in cancer cachexia management (p < 0.001). The number of symptoms used in cancer cachexia assessment (B = 0.42, p = 0.019), knowledge of cancer cachexia (B = 6.60, p < 0.001), and confidence in cancer cachexia management (B = 4.31, p = 0.010) were identified as critical factors according to the multiple regression analysis., Conclusion: The RDs' knowledge and confidence in cancer cachexia management were associated with their multimodal care practices., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: In opioid therapy for cancer pain, opioid-induced nausea and vomiting (OINV) occur in 20%-40% of patients during initial opioid treatment or increasing opioid doses. OINV result in failure to achieve pain relief due to poor opioid adherence. Therefore, antiemetics are used to prevent OINV, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for the prophylaxis of chemotherapy-induced nausea and vomiting., Methods and Analysis: This single-arm, single-centre exploratory study will evaluate the prophylactic antiemetic efficacy and safety of 5 mg olanzapine in patients with cancer pain who are withholding initial regular opioid therapy. Thirty-five patients will be enrolled. The primary endpoint is the proportion of patients achieving complete control (CC) of OINV during 5 days of opioid treatment. CC was defined as the absence of emetic episodes, no need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the complete response, defined as no emetic episodes and no use of rescue medication during the overall assessment period, the time from opioid initiation to first emetic episode, the time from opioid initiation to first rescue antiemetic administration, and adverse events graded by Patient-Reported Outcome (PRO) Common Terminology Criteria for Adverse Events (CTCAE) version 1.0 and CTCAE version 5.0., Ethics and Dissemination: This study protocol was approved by National Cancer Center Hospital Certified Review Board. The results will be used as preliminary data to conduct a validation study., Trial Registration Number: Japan Registry of Clinical Trials (jRCT) jRCTs031220008., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although cancer patients' activities of daily living (ADL) are reported to decline before death, ADL trajectories have not been sufficiently clarified due to limitations in the assessment and analysis methods., Objectives: To clarify the multiple trajectories of ADL in patients with terminal cancer using a comprehensive assessment measure., Design: This was a retrospective observational study., Setting/study Subjects: Cancer patients aged ≥18 years discharged at death from a single-center palliative care unit., Measurements: Functional Independence Measure (FIM) total scores for eight weeks retrospectively., Results: In total, 306 patients were analyzed. Group-based trajectory modeling analysis estimated four groups as the best model for the FIM trajectory over eight weeks using the following trajectories: (1) a No Decline group, in which ADL did not decline until just before death; (2) a Rapid Decline group, in which ADL declined rapidly two weeks before death from a trajectory similar to the No Decline group; (3) a Moderate Disability and Slow Decline group, in which the patient slowly declined from requiring mild-to-severe assistance; and (4) a Severe Disability group, in which the patient continuously required severe assistance., Conclusions: Multiple ADL trajectories were identified in the last eight weeks of life of patients with terminal cancer. These findings suggest that palliative care needs to be tailored to the characteristics of each patient., Competing Interests: No competing financial interests exist., (© Ryo Soeda et al., 2024; Published by Mary Ann Liebert, Inc.)

Aims: To describe nursing practices for financial toxicity management based on nurses' perceptions. Materials & methods: A survey was conducted with 615 oncology nurses in Japan, focusing on nurses' perspectives on the importance of financial toxicity, nursing practices to manage financial toxicity and factors inhibiting its management. Results: A total of 521 participated, of whom 266 respondents (51.1%) considered nurses' role important, and they engaged in a significantly higher proportion of nursing practices. Participants with greater perceptions of their role included certified or specialized nurses and nurses responsible for outpatient care. Conclusion: Interventions leveraging the expertise of certified or specialized nurses and nurses involved in outpatient care could help to spread proactive nurse practices addressing financial toxicity.

Background/aims: The precise incidence of symptomatic uncomplicated diverticular disease (SUDD) and its effects on the quality of life (QOL) remain unclear, particularly in Asian patients with right-sided SUDD. We assess the prevalence of SUDD and its impact on QOL in a real-world population., Methods: Five institutional cohorts of patients who received outpatient treatment for unexplained abdominal symptoms from January 15, 2020 to March 31, 2022, were included. All patients underwent colonoscopy. SUDD was defined as the presence of recurrent abdominal symptoms, particularly pain in the lower right or left quadrant lasting > 24 hours in patients with diverticulosis at the site of pain. The 36-item short-form health survey was used to assess QOL., Results: Diverticula were identified in 108 of 361 patients. Among these 108 patients, 31% had SUDD, which was right-sided in 39% of cases. Of the 50 patients with right-sided diverticula, 36% had SUDD, as did 15 of 35 patients with left-sided diverticula (43%). Among the 33 patients with SUDD, diverticula were right-sided, left-sided, and bilateral in 39%, 45%, and 15% of patients, respectively. Diarrhea was more frequent in the SUDD group than in the non-SUDD group. Patients with SUDD had significantly lower physical, mental, and role/social component scores than those without SUDD., Conclusions: It is important to recognize that patients with SUDD account for as high as 31% of outpatients with unexplained abdominal symptoms; these patients have diarrhea and a low QOL. The presence of right-sided SUDD was characteristic of Asian patients.

Objectives: Dyspnoea is a common and distressing symptom in patients with cancer. We aimed to analyse the association between dyspnoea and related factors and to estimate their causal relationship., Methods: A cross-sectional study was conducted. Patients with cancer with dyspnoea and a mean Numerical Rating Scale (NRS) of ≥3 over 24 hours were enrolled at 10 institutions in Japan from December 2019 to February 2021. The outcomes included dyspnoea, cough and pain NRS over 24 hours, Eastern Cooperative Oncology Group Performance Status, Hospital Anxiety and Depression Scale, Somatosensory Amplification Scale, opioids for dyspnoea and respiratory failure. Path analyses were conducted to estimate the direct and indirect paths with reference to dyspnoea and related factors., Results: A total of 209 patients were enrolled and 208 patients were included in the analysis. Cough worsened dyspnoea (β=0.136), dyspnoea increased emotional distress (β=1.104), emotional distress increased somatosensory amplification (β=0.249) and somatosensory amplification worsened cough (β=0.053) according to path analysis., Conclusion: There may be a vicious circle among dyspnoea and related factors: cough worsened dyspnoea, dyspnoea increased emotional distress, emotional distress increased somatosensory amplification and somatosensory amplification worsened cough. When treating dyspnoea in patients with cancer, managing these factors aimed at interrupting this vicious circle may be useful., Trial Registration Number: UMIN Clinical Trials Registry (UMIN000038820)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Osteoblastic bone reaction (OBR) refers to an increase in bone density at the site of bone metastasis or the appearance of new sclerotic bone lesions after anticancer treatment. OBR can be misunderstood as disease progression. In this study, we aimed to investigate the prevalence and details of OBR and its association with clinical outcomes in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with osimertinib., Methods: This was a single-center, retrospective cohort study. We reviewed patients who were diagnosed with EGFR-mutant NSCLC with bone metastasis and received osimertinib as a first-line treatment between February 2018 and October 2022. The OBR was evaluated by comparing baseline computed tomography (CT) scans with the first CT scan after treatment initiation., Results: A total of 45 patients were included in this study. Thirty-seven patients (82%) developed OBR. OBR developed in 94% (n = 16) of patients with sclerotic bone lesions (n = 17) at baseline. Similarly, OBR developed in lytic and mixed bone lesions in 76% and 82% of patients with lytic and mixed lesions, respectively. Progression-free survival (PFS) did not differ significantly between patients with (OBR group) and without OBR (non-OBR group) (median PFS, 24 months vs. 17 months; hazard ratio (HR), 0.62; 95% CI, 0.24-1.6; p = 0.31). In univariate analysis, the OBR group showed a trend toward longer skeletal-related events-free survival (SRE-FS) than the non-OBR group (median SRE-FS, 26 months vs. 12 months; HR, 0.53; 95% CI, 0.21-1.33; p = 0.16). Multivariate analysis showed OBR was a significant independent predictor of SRE-FS (HR, 0.35; 95% CI, 0.13-0.92; p = 0.034)., Conclusions: OBR developed in most patients with NSCLC and bone metastasis who received osimertinib treatment. The increased incidence of OBR in patients with EGFR-mutant NSCLC with bone metastasis treated with osimertinib should not be confused with disease progression, and treatment decisions should be made carefully., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Postoperative delirium is an important issue in cancer patients, affecting surgical outcomes and the quality of life. Ramelteon is a melatonin receptor agonist with high affinity for MT1 and MT2 receptors. Clinical trials and observational studies in Japan, including in surgical cancer patients, have shown efficacy of ramelteon in delirium prevention, with no serious safety concerns. However, clinical trials from the USA have reported conflicting results. A Japanese phase II study investigated the efficacy and safety of ramelteon for delirium prevention following gastrectomy in patients aged ≥75 years, with findings suggesting the feasibility of a phase III trial. The aim of this multi-centre, double-blind, randomized placebo-controlled phase III trial is to evaluate the effectiveness and safety of oral ramelteon for postoperative delirium prevention in cancer patients aged ≥65 years as advanced medical care. The trial protocol is described here., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Multimodal care for cancer cachexia is needed. This study examined factors associated with practicing multimodal cachexia care among physicians and nurses engaging in cancer care., Methods: This was a preplanned secondary analysis of a survey investigating clinicians' perspectives on cancer cachexia. Data of physicians and nurses were used. Data on knowledge, skills, and confidence in multimodal cachexia care were obtained. Nine items on practicing multimodal cachexia care were evaluated. Participants were divided into two groups as practicing multimodal cachexia care (above median value for the nine items) or not. Comparisons were made using the Mann-Whitney U test or chi-square test. Multiple regression analysis was performed to identify the factors of practicing the multimodal care., Results: Total of 233 physicians and 245 nurses were included. Significant differences were observed between the groups: female sex ( P = .025), palliative care versus oncology specialization ( P < .001), the number of clinical guidelines used ( P < .001), the number of symptoms used ( P = .005), training for cancer cachexia ( P = .008), knowledge on cancer cachexia ( P < .001), and confidence in cancer cachexia management ( P < .001). Palliative care specialization (partial regression coefficient [ B ] = 0.85; P < .001), the number of clinical guidelines used ( B = 0.44; P < .001), knowledge on cancer cachexia ( B , 0.94; P < .001), and confidence in cancer cachexia management ( B = 1.59; P < .001) were statistically significant in multiple regression analysis., Conclusion: Specialization in palliative care, specific knowledge, and confidence were associated with the practice of multimodal care for cancer cachexia.

Background: Tobacco control should be a higher public health priority in Japan. Some workplaces provide smoking cessation support and connect employees to effective smoking cessation treatments such as outpatient clinics. However, tobacco control measures have not been sufficiently implemented in Japan, especially in small- and medium-sized enterprises (SMEs), where resources are limited. Organizational commitment and consistent leadership are crucial to facilitate implementation, but research on whether supporting organizational leaders leads to health behavior changes among employees is limited., Methods: This hybrid type II cluster randomized effectiveness implementation trial (eSMART-TC) aims to examine the effects of interactive assistance for SME management on health and implementation outcomes. We will provide interactive assistance to employers and health managers for 6 months, aiming to promote the utilization of reimbursed smoking cessation treatments by public health insurance and to implement smoke-free workplaces. The intervention will consist of three strategies: supporting employees through campaigns, tailored ongoing facilitation, and ensuring executive engagement and support. The primary health and implementation outcomes will be salivary cotinine-validated 7-day point-prevalence abstinence rate, and the adoption of two recommended measures (promoting utilization of smoking cessation treatment and implementing smoke-free workplaces) 6 months after the initial session, respectively. Other outcomes for implementation (e.g., penetration of smoking cessation clinic visits), health (e.g., salivary cotinine-validated 7-day point-prevalence abstinence rate at 12 months), and process (e.g., adherence and potential moderating factors) will be collected via questionnaires, interviews, logbooks, and interventionists' notes at 6 and 12 months. An economic analysis will be undertaken to assess the cost-effectiveness of the implementation interventions at 12 months., Discussion: This will be the first cluster randomized controlled trial to evaluate the effectiveness of an implementation intervention with interactive assistance for employers and health managers in SMEs on smoking cessation and implementation of evidence-based tobacco control measures in SMEs. The findings of this trial targeting management in SMEs have the potential to accelerate the implementation of evidence-based smoking cessation methods as well as abstinence rates among employees in SMEs across Japan., Trial Registration: The study protocol has been registered in the UMIN Clinical Trials Registry (UMIN-CTR; ID: UMIN000044526). Registered on 06/14/2021., (© 2023. The Author(s).)

Background: Regorafenib, a multikinase inhibitor, causes a high frequency of hand-foot skin reactions (HFSRs). The present study evaluated the efficacy of topical aluminum chloride, a perspiration suppressant, in reducing the severity of hand-foot skin reactions (HFSRs) caused by regorafenib., Methods: The present single-arm study included patients with metastatic colorectal cancer receiving regorafenib. Aluminum chloride ointment was applied topically one week prior to the start of regorafenib treatment, and the observation period was 12 weeks. The primary endpoint was the incidence of regorafenib-related grade 3 HFSR. Secondary endpoints were the incidence of all grades of HFSR, time to any grade of HFSR, time to improvement from grade 2 or higher to grade 1 or lower, treatment discontinuation rate, treatment interruption rate or dosage reduction due to HFSR, and incidence of adverse effects of aluminum chloride., Results: In total 28 patients were enrolled, and 27 patients were analyzed. The incidence of grade 3 HFSR was 7.4%, meeting the primary endpoint. The incidence of all grades of HFSR was 66.7%, and the median time to the occurrence of any grade of HFSR was 15 days. No patients discontinued or reduced the regorafenib dosage because of HFSR. The most common reason for the interruption of regorafenib therapy was liver dysfunction in nine patients (33%) and HFSR in three patients (11%). No serious adverse events related to aluminum chloride were observed., Conclusions: Aluminum chloride ointment, a drug commonly used in routine practice to treat hyperhidrosis, is safe to use, has no serious side effects, and may be effective in reducing the occurrence of severe, regorafenib-related HFSR., Trail Registration: ClinicalTrials.gov. identifier: jRCTs031180096, Registered on 25/01/2019., (© 2023. The Author(s).)

Context: Although Systemic opioids are recommended as a pharmacological treatment for cancer-related dyspnea, their effectiveness and safety needs to be investigated in a real-world context OBJECTIVES: To evaluate the effectiveness and safety of systemic regular opioids for dyspnea in cancer patients, in the real-world palliative care practice., Methods: This was a multicenter prospective observational study. We consecutively enrolled adult cancer patients starting regular opioids (morphine, oxycodone, hydromorphone, or fentanyl) for dyspnea from 12 palliative care services across Japan. We evaluated dyspnea intensity using the Numerical Rating Scale (NRS) and Integrated Palliative Outcome Scale (IPOS) every 24 hours until 72 hours after starting opioids (T1-T3). We also evaluated common opioid-related adverse events (AEs) and other severe AEs., Results: We enrolled 402 cancer patients. The proportion of responders was 68.8% (95%confidence intervals (CI): 0.63-0.74) at T1, 75.7% (95%CI: 0.70-0.81) at T2, and 82.1% (95%CI: 0.76-0.87) at T3. The mean differences in dyspnea NRS from baseline were 1.73 (95%CI: 1.46-1.99) at T1, 1.99 (95%CI: 1.71-2.28) at T2, and 2.47 (95%CI:2.13-2.82) at T3. The most common treatment-emergent AE was somnolence with an incidence of the severe form of approximately 10% throughout the study period. In the multivariate analysis, baseline dyspnea NRS ≥6 had a positive correlation with dyspnea relief by systemic regular opioids, while liver metastasis, clinician-predicted survival days, and opioid tolerance had a negative correlation., Conclusion: Regular systemic opioids were effective for dyspnea in real-world cancer patients., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Cochlear implantation (CI) for the treatment of single-sided deafness (SSD) is a relatively new treatment modality. Although comparing the effectiveness of CI and contralateral routing of signal (CROS) hearing aids (HAs) is important, very few reports on this topic exist. In this study, objective assessments and subjective assessments were conducted to determine which SSD individuals would prefer CI or CROS HAs., Materials and Methods: Objective assessments (speech perception and sound localization) and subjective assessments (Hearing Handicap Inventory for Adults (HHIA), Abbreviated Profile of Hearing Aid Benefit (APHAB), MOS Short-Form 36-Item Health Survey version 2 (SF-36v2)) were performed on 87 SSD patients. Of the 87 SSD patients, 33 patients hoped for CROS HAs, and 17 patients hoped for CI. The CI group underwent subjective and objective assessments at 6 and 12 months postoperatively. The CROS HAs group underwent objective assessments at 1 month after wearing CROS HAs., Results: After the intervention, the localization ability was significantly improved in the CI group (p < 0.05) with no significant improvement in that of the CROS HAs group (p = 0.48). No significant improvement in speech perception in noise was observed in the CROS (Signal-to-Noise ratio + 10, p = 0.08; SN + 0, p = 0.17); however, a significant improvement in the CI group was observed at 12 months postoperatively. The APHAB subscale "background noise" and SF-36v2 health concepts of role-physical, general health, vitality, role-emotional, and mental health were significantly higher in the CI group., Conclusion: CI was superior to CROS HAs in speech perception in terms of noise and sound localization. Patients with postlingual acute-onset hearing loss and more handicaps and a more positive view of their hearing loss possibly tend to choose CI., Competing Interests: The authors disclose no financial relationships or conflict of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Objective: Recent studies have suggested that speech perception outcomes after cochlear implantation (CI) in prelingually deafened adults have improved with advances in CI technology and speech processing strategies. However, the outcomes vary from case to case. Communication mode has been reported in many studies as the factor that related to the post CI outcomes. This study aimed at investigating the post CI outcomes and the progress during 2 years for each communication mode., Material and Methods: The subjects were 17 prelingually deafened adults undergoing CI at our hospital between April 2013 and March 2019. We investigated preoperative factors affecting post CI outcomes. Also we analyzed post CI outcomes for each communication mode and compared preoperative factors for each communication mode., Results: Communication mode and preoperative discrimination score were the factor affecting on postoperative discrimination score. The speech perception score after CI improved significantly in the oral and lip-reading group and total communication group. The speech perception scores in postlingually deafened adults improved significantly during the first six months and became to plateau after CI. On the other hand, the scores of prelingually deafened adults tended to improve gradually after six months postoperatively. Furthermore, the degree of improvement and progress differed by each communication mode., Conclusion: The communication mode is important factors in predicting outcomes in prelingually deafened adults after CI. Long-term auditory training is important for prelingually deafened adults who use visual information as their preoperative method of communication., Competing Interests: Declaration of Competing Interest The authors declare no financial relationships or conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Timely implementation of the discussion process of advance care planning (ACP) is recommended. The communication attitude of healthcare providers is critical in ACP facilitation; thus, improving their communication attitudes may reduce patient distress and unnecessary aggressive treatment while enhancing care satisfaction. Digital mobile devices are being developed for behavioural interventions owing to their low space and time restrictions and ease of information sharing. This study aims to evaluate the effectiveness of an intervention programme using an application intended to facilitate patient questioning behaviour on improving communication related to ACP between patients with advanced cancer and healthcare providers., Methods and Analysis: This study uses a parallel-group, evaluator-blind, randomised controlled trial design. We plan to recruit 264 adult patients with incurable advanced cancer at the National Cancer Centre in Tokyo, Japan. Intervention group participants use a mobile application ACP programme and undergo a 30 min interview with a trained intervention provider for discussions with the oncologist at the next patient visit, while control group participants continue their usual treatment. The primary outcome is the oncologist's communication behaviour score assessed using audiorecordings of the consultation. Secondary outcomes include communication between patients and oncologists and the patients' distress, quality of life, care goals and preferences, and medical care utilisation. We will use a full analysis set including the registered participant population who receive at least a part of the intervention., Ethics and Dissemination: The study protocol was reviewed and approved by the Scientific Advisory Board of the Japan Supportive, Palliative and Psychosocial Oncology Group (Registration No. 2104) and the Institutional Review Board of the National Cancer Centre Hospital (registration No. 2020-500). Written informed consent is obtained from the patients. The results of the trial will be published in peer-reviewed scientific journals and presented at scientific meetings., Trial Registration Numbers: UMIN000045305, NCT05045040., Competing Interests: Competing interests: All authors declare that they have no competing interests directly related to this work. BN reports grants from Ono Pharmaceutical and Takeda Pharmaceutical, and personal fees from Ono Pharmaceutical, Bristol-Myers Squibb, Daiichi Sankyo and Taiho Pharmaceutical. TA reports grants from Daiichi Sankyo, Eisai, Fujifilm RI Pharma, MSD, Otsuka Pharmaceutical, and Shionogi, personal fees from Igaku-Shoin, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Sumitomo Dainippon Pharma, Eisai, Janssen Pharmaceutical, Kyowa Kirin, Eli Lilly, MSD, Meiji Seika Pharma, Mochida Pharmaceutical, NIPRO, Nippon Zoki Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Takeda Pharmaceutical and Viatris, and pending patents (2019-017498 & 2020-135195). TY reports grants or contracts from AC Medical, A2 Healthcare Corporation, EP Croit, ClinChoice., Japan Tobacco, Japan Media Corporation, Medidata Solutions, Ono Pharmaceutical, Asahi Intecc, 3H Clinical Trial, Medrio, Nipro Corporation, Intellim Corporation, Welby, 3H Medi Solution, Nipro Corporation, BaseConnect, Nobori, Puravida Technologies and Hemp Kitchen and grants to the affiliated institutions from Kyowa Kirin, Tsumura & CO., Daiichi Sankyo Company, Otsuka Pharmaceutical and Eisai, and consulting fees from EPS Corporation., Japan Tobacco, Medidata Solutions, Ono Pharmaceutical, Kowa Company, Chugai Pharmaceutical, Tsumura & Co., Daiichi Sankyo Company, Eisai, Asahi Intecc, Asahi Kasei Pharma Corporation, 3H Clinical Trial, Intellim Corporation, Takeda, AstraZeneca, Sonire Therapeutics, Seikagaku Corporation, and Merck & Co, and personal fees from Nipro Corporation., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)