Efficacy of StepAdd, a Personalized mHealth Intervention Based on Social Cognitive Theory to Increase Physical Activity Among Patients With Type 2 Diabetes Mellitus: Protocol for a Randomized Controlled Trial.

BACKGROUND: Increasing physical activity improves glycemic control in patients with type 2 diabetes (T2D). Mobile health (mHealth) interventions have been proven to increase exercise, but engagement often fades with time. As the use of health behavior theory in mHealth design can increase effectiveness, we developed StepAdd, an mHealth intervention based on the constructs of social cognitive theory (SCT). StepAdd improves exercise behavior self-efficacy and self-regulation through the use of goal-setting, barrier-identifying, and barrier-coping strategies, as well as automatic feedback functions. A single-arm pilot study of StepAdd among 33 patients with T2D showed a large increase in step count (mean change of 4714, SD 3638 daily steps or +86.7%), along with strong improvements in BMI (mean change of -0.3 kg/m2) and hemoglobin A1c level (mean change of -0.79 percentage points). OBJECTIVE: In this study, we aim to investigate the efficacy and safety of StepAdd, an mHealth exercise support system for patients with T2D, via a large, long, and controlled follow-up to the pilot study. METHODS: This is a randomized, open-label, multicenter study targeting 160 patients with T2D from 5 institutions in Japan with a 24-week intervention. The intervention group will record daily step counts, body weight, and blood pressure using the SCT-based mobile app, StepAdd, and receive feedback about these measurements. In addition, they will set weekly step count goals, identify personal barriers to walking, and define strategies to overcome these barriers. The control group will record daily step counts, body weight, and blood pressure using a non-SCT-based placebo app. Both groups will receive monthly consultations with a physician who will advise patients regarding lifestyle modifications and use of the app. The 24-week intervention period will be followed by a 12-week observational period to investigate the sustainability of the intervention's effects. The primary outcome is between-group difference in the change in hemoglobin A1c values at 24 weeks. The secondary outcomes include other health measures, measurements of steps, measurements of other behavior changes, and assessments of app use. The trial began in January 2023 and is intended to be completed in December 2025. RESULTS: As of September 5, 2023, we had recruited 44 patients. We expect the trial to be completed by October 8, 2025, with the follow-up observation period being completed by December 31, 2025. CONCLUSIONS: This trial will provide important evidence about the efficacy of an SCT-based mHealth intervention in improving physical activities and glycemic control in patients with T2D. If this study proves the intervention to be effective and safe, it could be a key step toward the integration of mHealth as part of the standard treatment received by patients with T2D in Japan. TRIAL REGISTRATION: Japan Registry of Clinical Trials (JRCT) jRCT2032220603; https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2032220603. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53514.

Feasibility, Tolerability, and Effectiveness of Transbronchial Interventions in Elderly Patients With Malignant Central Airway Obstruction: A Retrospective Single-institution Study.

BACKGROUND: In elderly patients with malignant central airway obstruction (MCAO), the treating physicians often hesitate to undertake transbronchial interventions (TBIs) as a palliative procedure in view of the advanced age of the patients. METHODS: We conducted this retrospective study to evaluate the differences in the feasibility, tolerability, and effectiveness of TBIs between elderly (aged 75 years old or above; elderly group; n=27) and nonelderly (aged below 75 years old; nonelderly group; n=50) patients with MCAO. The primary endpoint was the incidence of complications during (within 24 hours) and after (>24 hours) TBIs. RESULTS: The mean age of the patients was 81 years in the elderly group and 61 years in the nonelderly group. The complications encountered during/after TBI included endobronchial bleeding or hypoxemia requiring intubation occurring during the TBIs, and bacterial pneumonia, airway reocclusion, and stent migration occurring after the TBIs, although there was no difference in the frequency of complications during/after the TBIs between the elderly group and nonelderly group (26% vs. 30%, P =0.706). There was no difference in the percentage of patients in whom successful airway recanalization was achieved by TBI (93% vs. 80%, P =0.197), the percentage of patients who showed symptomatic improvement after the TBIs (67% vs. 76%, P =0.380) and the OS after the TBIs (6.1 vs. 7.3 months, P =0.704) between the 2 groups. CONCLUSION: TBIs can be undertaken without hesitation as a palliative procedure in elderly patients with MCAO.

Association of Cancer and Its Interaction with Conventional Risk Factors on Cardiovascular Disease Risk.

Introduction We sought to examine the association of cancer history with the incidence of individual cardiovascular disease events and to clarify whether the history of cancer modifies the relationship between conventional cardiovascular risk factors and incident cardiovascular disease. Methods This retrospective cohort study used the JMDC Claims Database, including 3,531,683 individuals. The primary endpoint was the composite cardiovascular disease outcome, which included myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Results During a follow-up, 144,162 composite endpoints were recorded. Individuals with a history of cancer had a higher risk of developing composite cardiovascular disease events (HR 1.26, 95% CI 1.22-1.29). The HRs for myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation were 1.11 (95% CI 0.98-1.27), 1.15 (95% CI 1.10-1.20), 1.11 (95% CI 1.05-1.18), 1.39 (95% CI 1.34-1.44), and 1.22 (95% CI 1.13-1.32), respectively. Individuals who required chemotherapy for cancer had a higher risk of developing cardiovascular disease. Although conventional risk factors (e.g., overweight/obesity, hypertension, and diabetes) were associated with incident composite cardiovascular disease even in individuals with a history of cancer, the total population-attributable fractions of conventional risk factors were less in individuals with a history of cancer. Conclusion Individuals with a history of cancer (particularly those requiring chemotherapy) have a higher risk of cardiovascular disease. Traditional risk factors are important in the development of cardiovascular disease in individuals with and without a history of cancer. In individuals with a history of cancer, however, the total population-attributable fractions of conventional risk factors decreased.

Effect of Smoke Evacuator on Reduction of Volatile Organic Compounds and Particles in Surgical Smoke: A Randomized Controlled Trial.

BACKGROUND: Surgical smoke is an occupational health problem and is increasingly recognized as a potential source of virus transmission. Dedicated smoke evacuators are used to protect against surgical smoke exposure. We tested the hypothesis that using smoke evacuators would reduce volatile organic compounds and the number of particles in surgical smoke during the laparotomy procedure. STUDY DESIGN: A randomized, double-blind clinical trial was conducted in patients undergoing laparotomy from June 11, 2021, to March 30, 2022, to compare the effectiveness of smoke evacuators with a control (registration, UMIN000044250). The primary outcome was a change in the acetaldehyde level. Secondary outcomes were changes in the formaldehyde level and particle count assessed by the particle size of 0.3, 0.5, 1.0, and 5.0 nm. RESULTS: A total of 42 patients were randomized and assessed (smoke evacuator group, n = 22 vs control group, n = 20). The acetaldehyde level was significantly lower in the smoke evacuator group than in the control group: mean (95% CI), 10.6 (3.7 to 17.5) vs 47.2 (19.9 to 74.5) µg/m 3 , p < 0.001. Similarly, the formaldehyde level was 72.2% lower in the smoke evacuator group than in the control group. Particle counts by each particle size category were 80% to 95% lower in the smoke evacuator group than in the control group (all, p < 0.001). CONCLUSIONS: Dedicated smoke evacuators reduced the level of acetaldehyde and formaldehyde, and the number of particles in surgical smoke, minimizing the potential exposure to volatile organic compounds and particle matters during surgery.

Long-term care facilities' response to the COVID-19 pandemic: An international, cross-sectional survey.

AIMS: To (i) assess the adherence of long-term care (LTC) facilities to the COVID-19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. DESIGN: Cross-sectional survey. METHODS: Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID-19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. RESULTS: The adherence was significantly higher among facilities with more pre-pandemic in-service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work-life imbalance. CONCLUSIONS: Pre-pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. IMPACT: This is the first study to comprehensively examine the adherence of LTC facilities to COVID-19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre-pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

The effectiveness of a thermography-driven preventive foot care protocol on the recurrence of diabetic foot ulcers in low-medical resource settings: An open-labeled randomized controlled trial.

BACKGROUND: Plantar temperature monitoring, along with a comprehensive preventive foot care approach, is utilized to prevent recurrence of diabetic foot ulcers. However, there is a lack of standardized protocols for individuals with diabetic foot ulcer history in low-medical resource countries. OBJECTIVE: This study investigated the efficacy of nurse-led, thermographic-evaluation-guided foot care in preventing diabetic foot ulcer recurrence in a low-medical resource country. DESIGN: Single-blind, 1:1 allocation randomized controlled trial. SETTINGS: Two wound care facilities with wound care nurse specialists in Indonesia. PARTICIPANTS: 120 patients with a diabetic foot ulcer history. INTERVENTION: In the intervention group, baseline risk assessment including smartphone thermography evaluation was performed. Personalized foot care and education were conducted monthly for participants whose thermographs showed increased foot lesion temperature at baseline risk assessment. The control group received usual care and education using a booklet at baseline. The follow-up period was six months. MAIN OUTCOME: Time to recurrence was evaluated using Kaplan-Meier survival analysis, and between-group comparisons were performed using the log-rank test. Potential risk factors were incorporated into the multivariate Cox regression model. Secondary outcomes included quality of life (European Quality of Life 5 Dimensions 3 Level Version) and foot care behavior, were analyzed using Mixed Models for Repeated Measures at baseline, third, and sixth follow-up (3 and 6 months from baseline). RESULTS: 120 participants (intervention 60, control 60) were randomized. The intervention group had a significantly lower recurrence rate than the control group (15% vs. 35%, p = 0.011) and a significant difference in time to ulceration (log-rank test, p = 0.009) after a 6-month follow-up period. Intervention care reduced the risk of diabetic foot ulcer recurrence by 59% (Hazard ratio 0.41, 95% confidence interval 0.18, 0.96, p = 0.039) in multivariate Cox regression analysis. On the third follow-up, total diabetic foot care behavior score (p < 0.001) was significantly improved by the intervention. On the sixth follow-up, mobility (p = 0.020), self-care (p = 0.023), pain/discomfort (p < 0.001), anxiety/depression (p = 0.016), EuroQol Visual Analogue Scale score (p = 0.002), and total diabetic foot care behavior score (p < 0.001) showed significant improvements in the intervention group. CONCLUSIONS: Foot care and personalized education delivered at a frequency based on the risk level assessed by thermography effectively reduced diabetic foot ulcer recurrence, and improved quality of life and foot care behaviors. REGISTRATION NUMBER: UMIN000039012. TWEETABLE ABSTRACT: Nurse-led diabetic foot care and education reduced diabetic foot ulcer recurrence in Indonesia.

Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicentre randomized controlled clinical trial.

OBJECTIVES: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 (COVID-19). METHODS: In this exploratory multicentre randomized controlled trial, patients were assigned to three groups within 5 days of symptom onset, with 10 participants in each group: nafamostat at either 0.2 mg/kg/h or 0.1 mg/kg/h or a standard-of-care group. The primary endpoint was area under the curve for decrease in SARS-CoV-2 viral load in nasopharyngeal samples from baseline to day 6. RESULTS: Of the 30 randomized patients, 19 received nafamostat. Overall, 10 patients received low-dose nafamostat, 9 patients received high-dose nafamostat, and 10 received standard-of-care. The detected viruses were Omicron strains. The regression coefficient for area under the curve for decrease in viral load as the response variable and nafamostat dose per body weight as the explanatory variable showed a significant relationship of -40.1 (95% confidence interval, -74.1 to -6.2; P = 0.022). Serious adverse events were not observed in either group. Phlebitis occurred in ca. 50% of patients treated with nafamostat. CONCLUSIONS: Nafamostat exerts virus load-reducing effects in patients with early-onset COVID-19.

Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.

BACKGROUND: The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. METHODS: We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. RESULTS: Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166

Differential prediction of high-sensitivity cardiac troponin-I, but not N-terminal pro-brain natriuretic peptide, in different pitavastatin doses on cardiovascular events in stable coronary artery disease.

BACKGROUND: This study aimed to examine whether high-sensitivity cardiac troponin-I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) could predict future major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients with high- or low-dose of pitavastatin. METHODS: This was a case-cohort analysis of the REAL-CAD study, a randomized trial of high- or low-dose (4 or 1 mg/day) pitavastatin therapy in patients with stable CAD. We examined the MACE risk according to the quartile of hsTnI and NT-proBNP at baseline. RESULTS: A total of 1336 and 1396 patients including 582 MACE cases were randomly examined into the hsTnI and NT-proBNP cohort, respectively. Both higher levels of hsTnI and NT-proBNP at baseline were significantly associated with increased risk of MACE (p < 0.001, respectively). When separately analyzed in statin dose, the higher marker levels were significantly associated with higher MACE risk in all cohorts (p < 0.001 in all cohorts). After multivariable adjustment, hsTnI levels were significantly associated with MACE risk in low-dose statin group (HR 2.54, p = 0.0001); however, in high-dose pitavastatin therapy, a significant association was diminished in MACE risk among the quartiles of baseline hsTnI levels (p = 0.154). Conversely in the NT-proBNP cohort, the association between NT-proBNP levels and MACE risk was constantly observed regardless of pitavastatin dose even after multivariable adjustment (both p < 0.0001). CONCLUSIONS: Patients with high hsTnI levels had high risk of MACE in low-dose statin group, but not in high-dose, suggesting that high-dose statin treatment might decrease MACE risk in stable CAD patients with high hsTnI levels.

Feasibility and Safety of Adjuvant Chemotherapy for Resected Colorectal Cancer in Patients With Renal Insufficiency: A Pooled Analysis of Individual Patient Data from Five Japanese Large-scale Clinical Trials.

BACKGROUND/AIM: The incidence of chemotherapy-related adverse events in colorectal cancer patients with renal insufficiency has been compared to patients with normal renal function in only a few studies. The purpose of this analysis was to verify the feasibility and safety of adjuvant chemotherapy for postoperative colorectal cancer patients with renal insufficiency. PATIENTS AND METHODS: Adverse events and discontinuation of adjuvant chemotherapy for patients with curatively resected locally advanced colorectal cancer were examined using a combined database of individual patient data obtained from five large-scale clinical trials (n=4,106). The renal function of patients was classified into Level (L) 1-2: ≥60 ml/min and L3-4: <60 ml/min. RESULTS: As Grade 3 adverse events, hematological toxicities, such as neutropenia and anemia, and gastrointestinal disorders, such as diarrhea and vomiting, were significantly more frequent in the L3-4 group. Moreover, the time-to-treatment discontinuation in the L3-4 group was higher (hazard ratio=1.21, p=0.0012). T factor, N factor, and creatinine clearance level were found to be independent risk factors for the discontinuation of adjuvant chemotherapy. In the subgroup analysis of FOLFOX, neutropenia and diarrhea were significantly common in the L3-4 group, but neurotoxicities were not different. There was no significant difference in the discontinuation of adjuvant FOLFOX. CONCLUSION: Adverse events of adjuvant chemotherapy in patients with resected colorectal cancer were associated with renal insufficiencies. Since adverse events have the potential to shorten the duration of treatment, especially when using chemotherapy without oxaliplatin, careful management, including dose reduction, may be important in patients with renal insufficiency.

Intraperitoneal paclitaxel combined with FOLFOX/CAPOX plus bevacizumab for colorectal cancer with peritoneal carcinomatosis (the iPac-02 trial): study protocol of a single arm, multicenter, phase 2 study.

BACKGROUND: The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial. METHODS: This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m2 is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110). RESULTS: We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies. CONCLUSION: Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.

Distribution of the follicular and luteal phase lengths and their age-dependent changes in Japanese women: A large population study.

Purpose: The current definition of menstrual cycle length in a Japanese woman is different from those of WHO definition, and the original data are outdated. We aimed to calculate the distribution of follicular and luteal phases length in modern Japanese women with various menstrual cycles. Methods: This study determined the lengths of the follicular and luteal phases of Japanese women using basal body temperature data collected via a smartphone application from 2015 to 2019, and the data were analyzed using the Sensiplan method. Over 9 million temperature readings from more than 80 000 participants were analyzed. Results: The mean duration of the low-temperature (follicular) phase averaged 17.1 days and was shorter among participants aged 40-49 years. The mean duration of the high-temperature (luteal) phase was 11.8 days. The variance and maximum-minimum difference of the length of the low temperature period were significant in women under 35 years old than women aged more than 35 years. Conclusions: The shortening of the follicular phase in women aged 40-49 years implied a relationship with the rapid decline of ovarian reserve in these women, and the age 35 years old was turning point of ovulatory function.

The clinical impacts of postoperative complications after colon cancer surgery for the clinical course of adjuvant treatment and survival.

AIM: We investigated whether or not postoperative complications (POCs) themselves have a negative survival impact or indirectly worsen the survival due to insufficient adjuvant chemotherapy in a pooled analysis of two large phase III studies performed in Japan PATIENTS AND METHODS: The study examined the patients who enrolled in 1304, phase III study comparing the efficacy of 6 and 12 months of capecitabine as adjuvant chemotherapy for stage III colon cancer patients and in 882, a phase III study to confirm the tolerability of oxaliplatin, fluorouracil, and l-leucovorin in Japanese stage II/III colon cancer patients. In our study, POCs were defined as the following major surgical complications: anastomotic leakage, pneumonia, bowel obstruction/ileus, surgical site infection, postoperative bleeding, urinary tract infection, and fistula. Patients were classified as those with POCs (C group) and those without POCs (NC group). RESULTS: A total of 2095 patients were examined in the present study. POCs were observed in 169 patients (8.1%). The overall survival (OS) rates at 5 years after surgery were 75.3% in the C group and 86.5% in the NC group (p = 0.0017). The hazard ratio of POCs for the OS in multivariate analysis was 1.70 (95% confidence interval, 1.19 to 2.45; p = 0.0040). The time to adjuvant treatment failure (TTF) of adjuvant chemotherapy was similar between the groups, being 68.6% in the C group and 67.1% in the NC group for the 6-month continuation rate of adjuvant chemotherapy. The dose reduction rate of adjuvant chemotherapy and adjuvant treatment suspension rate were also similar between the groups (C vs. NC groups: 45.0% vs. 48.7%, p = 0.3520; and 52.7% vs. 55.0%, p = 0.5522, respectively). CONCLUSION: POCs were associated with a poor prognosis but did not affect the intensity of adjuvant chemotherapy. These results suggested that POCs themselves negatively influence the survival.

Verification study on the catheterization of an upper arm vein using the new long peripheral intravenous catheter to reduce catheter failure incidence: A randomized controlled trial.

Intravenous infusion using a peripheral intravenous catheter (PIVC) is often complicated by catheter failure (CF). We hypothesized that catheterization of an upper arm vein instead of a forearm vein may help prevent CF. This study was designed to compare the incidence of CF in patients receiving hyper-stimulant drugs when catheters are placed in the forearm using short PIVCs (SPCs) with that when catheters are placed in the upper arm using the new long PIVCs. Patients admitted to a university hospital in Tokyo, Japan were enrolled in this study and were assigned to the SPC or the new long PIVC group. The primary outcome was the incidence of CF until 7 days. The secondary outcomes were the number of CFs per 1,000 days, the duration of the indwelling catheter, and the presence of thrombi and subcutaneous edema. Forty-seven patients were analyzed (median age, 67.0 years). The incidence of CF was 0% in the new long PIVCs and 32.0% (8 catheters) in the SPCs (p = 0.007), and the number of CF per 1,000 days was 0/1,000 and 81.7/1,000 days, respectively (p = 0.001). A significant difference in the duration of the indwelling catheter until CF occurrence was observed between the two groups (p = 0.004). Thrombi and subcutaneous edema were observed more frequently in the SPC group (p < 0.001). Catheterization of an upper arm vein using the new long PIVC to administer a hyper-stimulant drug might reduce CF compared with catheterization of a forearm vein using SPC.

Long-term Outcomes of Non-vascularized Multilayer Fascial Closure Technique for Dural Repair in Endoscopic Transnasal Surgery: Efficacy, Durability, and Limitations.

OBJECTIVE: Non-vascularized multilayer fascial closure technique (NMFCT) can be used instead of nasoseptal flap reconstruction for dural repair in endoscopic transnasal surgery (ETS); however, due to the lack of blood supply, its long-term durability and possible limitations need to be clarified. METHODS: This was a retrospective study on patients who underwent ETS with intraoperative cerebrospinal fluid (CSF) leakage. We assessed the postoperative and delayed CSF leakage rates and the associated risk factors. RESULTS: Among 200 ETSs with intraoperative CSF leakage, 148 (74.0%) ETSs were performed for skull base pathologies other than pituitary neuroendocrine tumor. The mean follow-up period was 34.4 months. Esposito grade 3 leakage was confirmed in 148 (74.0%) cases. NMFCT was used either with (67 [33.5%]) or without (133 [66.5%]) lumbar drainage. There were 10 cases (5.0%) of postoperative CSF leakage that necessitated reoperation. In 4 other cases (2.0%), CSF leakage was suspected but lumbar drainage alone successfully restored the condition. Multivariate logistic regression analyses revealed that posterior skull base location (P < 0.01, odds ratio 11.5, 95% CI 1.99-2.17 × 102) and craniopharyngioma pathology (P = 0.03, odds ratio 9.4, 95% CI 1.25-1.92 × 102) were significantly associated with postoperative CSF leakage. No delayed leakage occurred during the observation period except for 2 patients who underwent multiple radiotherapies. CONCLUSIONS: NMFCT is a reasonable alternative with long-term durability, though vascularized flap may be a better choice for cases in which vascularity of the surrounding tissues is significantly impaired due to interventions including multiple radiotherapies.

Age-Dependent Hemorrhage Risk and Obliteration Benefit After Radiosurgery for Brain Arteriovenous Malformation.

PURPOSE: Because patients with untreated brain arteriovenous malformations (BAVMs) are at variable risks of cerebral hemorrhage and associated mortality and morbidity, it is essential to identify patient populations who benefit most from prophylactic interventions. This study aimed to examine age-dependent differences in the therapeutic effect of stereotactic radiosurgery (SRS) on BAVMs. METHODS AND MATERIALS: This retrospective observational study enrolled patients with BAVMs who underwent SRS at our institution between 1990 and 2017. The primary outcome was post-SRS hemorrhage, and the secondary outcomes included nidus obliteration, post-SRS early signal changes, and mortality. To investigate age-related differences in outcomes after SRS, we performed age-stratified analyses using the Kaplan-Meier analysis and weighted logistic regression with the inverse probability of censoring weighting (IPCW). To address significant differences in patient baseline characteristics, we also performed inverse probability of treatment weighting (IPTW) adjusted for possible confounders to investigate age-related differences in outcomes after SRS. RESULTS: A total of 735 patients with 738 BAVMs were stratified by age. Age-stratified analysis using a weighted logistic regression model with IPCW showed a direct correlation between patient age and post-SRS hemorrhage (odds ratio [OR], 95% confidence interval [CI], and P value: 2.20, 1.34-3.63, and .002 at 18 months; 1.86, 1.17-2.93, and .008 at 36 months; and 1.61, 1.05-2.48, and .030 at 54 months, respectively). The age-stratified analysis also showed an inverse relationship between age and obliteration over the first 42 months after SRS (OR, 95% CI, and P value: 0.05, 0.02-0.12, and <.001 at 6 months; 0.55, 0.44-0.70, and <.001 at 24 months; and 0.76, 0.63-0.91, and .002 at 42 months, respectively). These results were also confirmed with the IPTW analyses. CONCLUSIONS: Our analysis demonstrated that patients' age at SRS is significantly associated with hemorrhage and the nidus obliteration rate after treatment. In particular, younger patients are more likely to exhibit reduced cerebral hemorrhages and achieve earlier nidus obliteration compared with older patients.

Blood levels of nicotinic acid negatively correlate with hearing ability in healthy older men.

BACKGROUND: Age-related hearing loss (ARHL) is a common phenomenon observed during aging. On the other hand, the decrease in Nicotinamide adenine dinucleotide (NAD +) levels is reported to be closely related to the age-related declines in physiological functions such as ARHL in animal studies. Moreover, preclinical studies confirmed NAD + replenishment effectively prevents the onset of age-related diseases. However, there is a paucity of studies on the relationship between NAD+ metabolism and ARHL in humans. METHODS: This study was analyzed the baseline results of our previous clinical trial, in which nicotinamide mononucleotide or placebo was administered to 42 older men (Igarashi et al., NPJ Aging 8:5, 2022). The correlations between blood levels of NAD+-related metabolites at baseline and pure-tone hearing thresholds at different frequencies (125, 250, 500, 1000, 2000, 4000, and 8000 Hz) in 42 healthy Japanese men aged > 65 years were analyzed using Spearman's rank correlation. Multiple linear regression analysis was performed with hearing thresholds as the dependent variable and age and NAD+-related metabolite levels as independent variables. RESULTS: Positive associations were observed between levels of nicotinic acid (NA, a NAD+ precursor in the Preiss-Handler pathway) and right- or left-ear hearing thresholds at frequencies of 1000 Hz (right: r = 0.480, p = 0.001; left: r = 0.422, p = 0.003), 2000 Hz (right: r = 0.507, p < 0.001, left: r = 0.629, p < 0.001), and 4000 Hz (left: r = 0.366, p = 0.029). Age-adjusted multiple linear regression analysis revealed that NA was an independent predictor of elevated hearing thresholds (1000 Hz (right): p = 0.050, regression coefficient (ß) = 1610; 1000 Hz (left): p = 0.026, ß = 2179; 2000 Hz (right): p = 0.022, ß = 2317; 2000 Hz (left): p = 0.002, ß = 3257). Weak associations of nicotinic acid riboside (NAR) and nicotinamide (NAM) with hearing ability were observed. CONCLUSIONS: We identified negative correlations between blood concentrations of NA and hearing ability at 1000 and 2000 Hz. NAD+ metabolic pathway might be associated with ARHL onset or progression. Further studies are warranted. TRIAL REGISTRATION: The study was registered at UMIN-CTR (UMIN000036321) on 1st June 2019.

Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan.

Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA-RNA panel as well as a paired tumor-normal matched test. Two hundred patients underwent TOP as part of Advanced Medical Care B with approval from the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were carried out in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty-two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those 30 transcripts, 6 had treatment implications and 4 had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647).

Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia.

OBJECTIVES: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19. METHODS: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO2). RESULTS: There was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group. CONCLUSION: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group.