Older phase 2 cardiac rehabilitation patients engaged in gardening maintained physical function during the COVID-19 pandemic.

This study aimed to clarify the effects of gardening on hemodynamic response, rating of perceived exertion (RPE) during exercise, and body weight in patients in whom phase 2 cardiac rehabilitation (CR) was interrupted due to the Coronavirus disease 2019 (COVID-19) pandemic. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. Patients under the age of 65 were excluded. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the gardener group and the non-gardener group. Forty-one patients were enrolled in the final analysis. After CR interruption, the gardener group did not show any significant difference in all items, whereas the non-gardener group experienced significant increase in HR (Peak) (p = 0.004) and worsening of the Borg scale scores for both dyspnea and lower extremity fatigue (p = 0.039 and p = 0.009, respectively). Older phase 2 CR patients engaged in gardening did not show any deterioration in hemodynamic response or RPE during exercise, despite CR interruption and refraining from going outside. Gardening may be recommended as one of the activities that can maintain or improve physical function in older phase 2 CR patients during the COVID-19 pandemic.

A single-center analysis of the survival benefits of adjuvant gemcitabine chemotherapy for biliary tract cancer.

BACKGROUND: Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC. METHODS: We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m(2). Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m(2) in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders. RESULTS: Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28-0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07-0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02-0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01-0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03-0.85; interaction, P = 0.13). CONCLUSIONS: Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.

Cultural engagement and prevalence of pain in socially isolated older people: a longitudinal modified treatment policy approach.

Background: It remains uncertain whether cultural engagement positively influences the reduction of pain risk, particularly depending on the social isolation status. The aim of this study was to examine the impact of cultural engagement on the reduction of pain prevalence over a 6-year follow-up period among older people, particularly those experiencing different dimensions of social isolation. Methods: This study was a prospective longitudinal study. We analysed the English Longitudinal Study of Ageing cohort, consisting of 6468 community-dwelling adults aged ≥50 years old who provided data in waves 6 (2012-2013), 7 (2014-2015), 8 (2016-2017), and 9 (2018-2019). Self-reported cultural engagement (going to museums, art galleries, exhibitions, the theatre, concerts, or the opera) measured in waves 6-8 was used as the exposure variable. Meanwhile self-reported moderate-to-severe pain in wave 9 was used as the outcome variable. Social isolation was considered in waves 6-8, and the possibility of effect modification was captured by assessing each component of the social isolation index: not married or cohabiting with a partner, fewer than monthly contact with children/other immediate family/friends, and not engaging in any organisations, religious groups, or committees. Findings: The estimated pain prevalence was 29.2% (95% confidence interval, 28.1-30.3; reference) after adjusting for time-variant, time-invariant, and loss to follow-up factors. Cultural engagement led to a reduction in pain prevalence to 24.1% for all individuals, representing a decrease of 5.1% (95% confidence interval, 0.6-9.6; P-value, 0.03). In older people who were not married or cohabiting, cultural engagement resulted in a decrease in pain prevalence to 25.8%, a reduction of 3.4% (95% confidence interval, 0.4-6.4; P-value, 0.01). For those with less frequent contact with close family members, the pain prevalence decreased to 25.3%, a reduction of 3.9% (95% confidence interval, 0.2-7.6; P-value, 0.03). Meanwhile, other dimensions of social isolation did not show a significant reduction in pain prevalence. Interpretation: Cultural engagement may help to reduce the risk of pain in socially isolated older adults. Those who were single or living alone and had less frequent contact with immediate family were particularly vulnerable. While cultural engagement might help certain socially isolated older people feel better, its effectiveness varies, highlighting the need for targeted interventions. Funding: The Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number (22K17648, Ikeda).

Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA).

BACKGROUND: Gemcitabine/cisplatin (GC) combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). No randomized clinical trials have been able to demonstrate the survival benefit over GC during the past decade. In our previous phase II trial, adding S-1 to GC (GCS) showed promising efficacy and we aimed to determine whether GCS could improve overall survival compared with GC for patients with advanced BTC. METHODS: We performed a mulitcenter, randomized phase III trial across 39 centers. Enrolled patients were randomly allocated (1:1) to either the GCS or GC arm. The GCS regimen comprised gemcitabine (1000 mg/m2 ) and cisplatin (25 mg/m2 ) infusion on day 1 and 80 mg/m2 of S-1 on days 1-7 every 2 weeks. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response rate (RR), and adverse events (AEs). This study is registered with Clinical trial identification: NCT02182778. RESULTS: Between July 2014 and February 2016, 246 patients were enrolled. The median OS and 1-year OS rate were 13.5 months and 59.4% in the GCS arm and 12.6 months and 53.7% in the GC arm, respectively (hazard ratio [HR] 0.79, 90% confidence interval [CI]: 0.628-0.996; P = .046 [stratified log-rank test]). Median PFS was 7.4 months in the GCS arm and 5.5 months in the GC arm (HR 0.75, 95% CI: 0.577-0.970; P = .015). RR was 41.5% in the GCS arm and 15.0% in the GC arm. Grade 3 or worse AEs did not show significant differences between the two arms. CONCLUSIONS: GCS is the first regimen which demonstrated survival benefits as well as higher RR over GC in a randomized phase III trial and could be the new first-line standard chemotherapy for advanced BTC. To exploit the advantage of its high RR, GCS is now tested in the neoadjuvant setting in a randomized phase III trial for potentially resectable BTC.

A Mobile Health-Based Disease Management Program Improves Blood Pressure in People With Multiple Lifestyle-Related Diseases at Risk of Developing Vascular Disease　- A Retrospective Observational Study.

Background: The overlap of multiple lifestyle-related diseases increases the risk of vascular diseases. This study investigated the effects of a mobile health (mHealth)-based disease management program on blood pressure and the safety of this program in people with multiple lifestyle-related diseases at risk of developing vascular disease. Methods and Results: This retrospective observational study was conducted using secondary data collected by PREVENT Inc. People with a full history of hypertension, diabetes, and dyslipidemia and who participated in a 6-month mHealth-based disease management program were included in the study. The primary outcome was blood pressure. Adverse events during the program were investigated to evaluate safety. In total, 125 participants (mean [±SD] age 55.3±6.2 years) were examined. Systolic and diastolic blood pressure were significantly lower after the intervention than at baseline (systolic blood pressure, 128.0±12.3 vs. 131.9±12.7 mmHg [P<0.001]; diastolic blood pressure, 81.2±9.3 vs. 83.6±8.9 mmHg; P=0.003). No serious adverse events occurred during the program. Conclusions: The present results indicate that the mHealth-based disease management program may reduce blood pressure in people with multiple lifestyle-related diseases at risk of developing vascular disease and that the program is safe. These findings will help shape future health instructions using mHealth-based interventions.

Effects of a multidisciplinary intervention to promote physical activity in patients with stroke undergoing rehabilitation: study protocol for the ActivePAS pilot randomised controlled trial.

Introduction: Physical activity after stroke is related to functional recovery and outcomes. To optimise physical activity adapted to a patient's walking ability and characteristics, multidisciplinary support and interventions are required. The Activate Physical Activity for Stroke pilot randomised controlled trial aims to assess the safety and feasibility of a multidisciplinary intervention that promotes physical activity in patients who had a stroke undergoing rehabilitation. Methods and analysis: This single-centre, randomised controlled trial will enrol 32 patients who had a stroke undergoing rehabilitation. Patients who had a stroke with the ability to walk 50 m with at least hand assistance, regardless of the use of braces or walking aids, and aged≥20 years will be randomly allocated to a multidisciplinary intervention group or control group. Patients in the intervention group will receive instructions for the self-monitoring of hospitalised physical activity and support to promote physical activity by multidisciplinary staff. The primary outcome of the present study is the safety (adverse events) and feasibility (retention and completion rates) of the multidisciplinary intervention. We assess physical activity using a triaxial accelerometer (UW-204NFC, A&D Company) as one of the secondary outcomes. Ethics and dissemination: The present study has been approved by the Research Ethics Committee of Konan Women's University and the Ethics Committee of Nishi-Kinen Port Island Rehabilitation Hospital. We will disseminate the results of the present study through a peer-reviewed manuscript and presentations at international conferences. Trial registration number: UMIN000046731.

Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101).

BACKGROUND: Biliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy cannot tolerate the standard gemcitabine regimen (1,000 mg/m2 on days 1, 8, and 15 every 4 weeks) due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy determined that the recommended dose is 1,000 mg/m2 on days 1 and 15 every 4 weeks. Here, we evaluate the pharmacokinetics and pharmacodynamics of gemcitabine in these subjects. METHODS: We evaluated BTC patients scheduled to undergo surgical resection with major hepatectomy followed by gemcitabine therapy. A pharmacokinetic evaluation of gemcitabine and its main metabolite, 2',2'-difluorodeoxyuridine (dFdU), was conducted at the initial administration of gemcitabine, which was given by intravenous infusion over 30 min at a dose of 800-1,000 mg/m2. Physical examination and adverse events were monitored for 12 weeks. RESULTS: Thirteen patients were enrolled from August 2011 to January 2013, with 12 ultimately completing the pharmacokinetic study. Eight patients had hilar cholangiocarcinoma, three had intrahepatic cholangiocarcinoma, and one had superficial spreading type cholangiocarcinoma. The median interval from surgery to first administration of gemcitabine was 65.5 days (range, 43-83 days). We observed the following toxicities: neutropenia (n = 11, 91.7%), leukopenia (n = 10, 83.3%), thrombocytopenia (n = 6, 50.0%), and infection (n = 5, 41.7%). Grade 3 or 4 neutropenia was observed in 25% (n = 3) of patients. There were differences in clearance of gemcitabine and dFdU between our subjects and the subjects who had not undergone hepatectomy. CONCLUSION: Major hepatectomy did not affect the pharmacokinetics of gemcitabine or dFdU. TRIAL REGISTRATION: UMIN-CTR in (JPRN) UMIN000005109.

Therapeutic applications of curcumin for patients with pancreatic cancer.

A number of preclinical studies have demonstrated anticancer effects for curcumin in various types of tumors, including pancreatic cancer. Curcumin has anticancer effects both alone and in combination with other anticancer drugs (e.g., gemcitabine, 5-fluorouracil, and oxaliplatin), and it has been shown to modulate a variety of molecular targets in preclinical models, with more than 30 molecular targets identified to date. Of these various molecules, NF-κB is thought to be one of the primary targets of curcumin activity. Based on these promising preclinical results, several research groups, including our own, have progressed to testing the anticancer effects of curcumin in clinical trials; however, the poor bioavailability of this agent has been the major challenge for its clinical application. Despite the ingestion of gram-level doses of curcumin, plasma curcumin levels remain at low (ng/mL) levels in patients, which is insufficient to yield the anticancer benefits of curcumin. This problem has been solved by the development of highly bioavailable forms of curcumin (THERACURMIN), and higher plasma curcumin levels can now be achieved without increased toxicity in patients with pancreatic cancer. In this article, we review possible therapeutic applications of curcumin in patients with pancreatic cancer.