Emergency resuscitative thoracotomy in severe trauma: Analysis of the nation-wide registry data in Japan.

Aim: Emergency resuscitative thoracotomy is a potentially lifesaving procedure for patients with cardiac pulmonary arrest and profound circulatory failure resulting from a severe injury. However, survival rate post-emergency resuscitative thoracotomy shows considerable variation, with many studies constrained by limited sample sizes and ambiguous criteria for inclusion. Herein, we assessed the outcomes of emergency resuscitative thoracotomy and identified predictors of futility using Japan Trauma Data Bank data. Methods: Data of patients aged ≥18 years between 2004 and 2019 were analyzed. The primary outcome measure was survival at discharge. Descriptive statistics were used to compare the survivor and nonsurvivor groups. A multivariable logistic regression analysis was conducted to identify predictors of survival in patients undergoing emergency resuscitative thoracotomy while adjusting for confounding factors. Results: Among patients who underwent emergency resuscitative thoracotomy, 684/5062 (13.5%) survived. Age <65 years (adjusted odds ratio, 1.351; 95% confidence interval, 1.130-1.615; p < 0.001), absence of cardiac pulmonary arrest on emergency department arrival (adjusted odds ratio, 1.694; 95% confidence interval, 1.280-2.243; p < 0.01), Injury Severity Score <16 (adjusted odds ratio, 2.195; 95% confidence interval, 1.611-2.992; p < 0.01), and penetrating injury (adjusted odds ratio, 1.834; 95% confidence interval, 1.384-2.431; p < 0.01) were identified as factors associated with survival at discharge. Conclusion: The survival rate for emergency resuscitative thoracotomy in Japan stands at approximately 13.5%. Factors contributing to survival include younger age, absence of cardiopulmonary arrest at emergency department arrival, lack of severe trauma, and sustaining penetrating injuries.

Role of Small Dense Low-density Lipoprotein Cholesterol in Cardiovascular Events in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Receiving Statin Treatment.

AIM: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. METHODS: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. RESULTS: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL. CONCLUSIONS: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL.

The Association between Sleep and Bone Mineral Density: Cross-Sectional Study Using Health Check-up Data in a Local Hospital in Japan.

This study aimed to investigate the association between daily sleep duration of <7 hours and lower bone mineral density (BMD) using data from annual health check-ups conducted in Japan between 2020 and 2022. Multivariate regression models were used, where BMD was the objective variable and daily sleep duration (<5 hours, 5 to <7 hours, 7 to <9 hours [reference], ≥9 hours) was the exposure variable adjusted for age, body mass index, physical activity, smoking status, and alcohol intake for men and women and further adjusted for menopausal status for women. The association between insomnia and BMD was also investigated. BMD was determined using calcaneal quantitative ultrasound and expressed as a percentage of the young adult mean (%YAM). In total, 896 men and 821 women were included. Median age was 54 years (interquartile range [IQR]: 46 to 64) for men and 55 years (IQR: 46 to 64) for women). Median BMD for men and women was 79%YAM (IQR: 71 to 89) and 75%YAM (IQR: 68 to 84), respectively. Approximately 80% of men and women slept <7 hours daily. Multivariate regression showed no association between sleep duration and BMD in men. However, women who slept 5 to <7 hours daily had significantly higher BMD by 3.9% compared with those who slept 7 to<9 hours (p = 0.004). No association between insomnia and BMD was found. Overall, a daily sleep duration of <7 hours was not independently associated with lower BMD compared to those who slept 7 to <9 hours in men and women. However, as there is evidence of both shorter and longer sleep durations being associated with an increased risk of adverse events, including cardiovascular events, our result needs to be interpreted with caution. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Prognostication of Patients with Pulmonary Thromboembolism with and without Residual Deep Vein Thrombosis: A Subanalysis of the J'xactly Study.

Objectives: It is unclear whether patients with acute pulmonary thromboembolism (PE) with and without residual deep vein thrombosis (DVT) have different prognoses, and there is debate over whether inferior vena cava filters (IVCFs) should be used in conjunction with oral anticoagulants in patients with venous thromboembolism (VTE). Materials and Methods: The J'xactly involved 1,016 patients and was a multicenter, prospective, observational research. In this subanalysis, 419 patients with PE with or without residual DVT who received rivaroxaban with or without IVCFs between February 2016 and April 2018 in Japan were examined. Results: Of 419 patients with PE, 320 had residual DVT. There was no difference between the groups with and without DVT in terms of the percentage of patients who experienced symptomatic PE recurrence (2.8% [9/320] vs. 3.0% [3/99]) or who died from VTE-related complications (0.9% [3/320] vs. 1.0% [1/99]). The percentages of patients with symptomatic PE recurrence were 0% and 3.2%, and the percentages of patients who died from VTE-related causes were 0% and 1.1%, respectively, in the groups with (n=39) and without (n=281) IVCF, albeit not being statistically different. Conclusion: Patients with PE with and without residual DVT did not have a different incidence of symptomatic PE recurrence. These results require additional study to be confirmed.

Rivaroxaban treatment for asymptomatic venous thromboembolism: insights from the J'xactly study.

BACKGROUND: An established treatment strategy for asymptomatic pulmonary embolism (PE) or deep vein thrombosis (DVT) remains uncertain in Japan; therefore, in this study, we clarify the characteristics and outcomes of symptomatic compared to asymptomatic patients with PE or DVT. METHODS: This prospective, multicenter sub-analysis of the J'xactly study in Japan included 1,016 patients (mean age, 68; 41% male) with venous thromboembolism (VTE) treated with rivaroxaban. RESULTS: Asymptomatic PE patients (47% of PE patients) were more likely to have active cancer and asymptomatic proximal DVT at lower severity than symptomatic PE patients, despite no differences in age, sex, or the proportion receiving intensive 30 mg/day-rivaroxaban. Patients with asymptomatic DVT (34% of DVT patients) were older, had higher rates of female sex, active cancer, and distal DVT, and received shorter, less intense rivaroxaban treatment. Incidences did not differ between asymptomatic and symptomatic PE patients for recurrent symptomatic VTE (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.22-1.62; P = 0.31) or major bleeding (HR, 0.68; 95% CI, 0.20-2.33; P = 0.58), nor between asymptomatic and symptomatic DVT patients for recurrent symptomatic VTE (HR, 0.56; 95% CI, 0.23-1.40; P = 0.21) and major bleeding (HR, 1.47; 95% CI, 0.54-3.97; P = 0.45). CONCLUSIONS: The real-world composite adverse event rate for treatment with rivaroxaban, as physician-adjusted for dose and duration, was similar for asymptomatic and symptomatic patients regardless of the presence of PE or DVT, suggesting a favorable safety profile for potential rivaroxaban treatment for asymptomatic VTE.

Gut microbial carbohydrate metabolism contributes to insulin resistance.

Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes1,2. Previous metagenomic studies have described the characteristics of gut microbiota and their roles in metabolizing major nutrients in insulin resistance3-9. In particular, carbohydrate metabolism of commensals has been proposed to contribute up to 10% of the host's overall energy extraction10, thereby playing a role in the pathogenesis of obesity and prediabetes3,4,6. Nevertheless, the underlying mechanism remains unclear. Here we investigate this relationship using a comprehensive multi-omics strategy in humans. We combine unbiased faecal metabolomics with metagenomics, host metabolomics and transcriptomics data to profile the involvement of the microbiome in insulin resistance. These data reveal that faecal carbohydrates, particularly host-accessible monosaccharides, are increased in individuals with insulin resistance and are associated with microbial carbohydrate metabolisms and host inflammatory cytokines. We identify gut bacteria associated with insulin resistance and insulin sensitivity that show a distinct pattern of carbohydrate metabolism, and demonstrate that insulin-sensitivity-associated bacteria ameliorate host phenotypes of insulin resistance in a mouse model. Our study, which provides a comprehensive view of the host-microorganism relationships in insulin resistance, reveals the impact of carbohydrate metabolism by microbiota, suggesting a potential therapeutic target for ameliorating insulin resistance.

Reduced reactive hyperemia of the brachial artery in diabetic patients assessed by repeated measurements: The FMD-J B study.

Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia.

Genotyping of Mycoplasma pneumoniae strains isolated in Japan during 2019 and 2020: spread of p1 gene type 2c and 2j variant strains.

We characterized 118 Mycoplasma pneumoniae strains isolated from three areas of Japan (Saitama, Kanagawa, and Osaka) during the period of 2019 and 2020. Genotyping of the p1 gene in these strains revealed that 29 of them were type 1 lineage (29/118, 24.6%), while 89 were type 2 lineage (89/118, 75.4%), thereby indicating that type 2 lineage was dominant in this period. The most prevalent variant of type 2 lineage was type 2c (57/89, 64%), while the second-most was type 2j, a novel variant identified in this study (30/89, 33.7%). Type 2j p1 is similar to type 2 g p1, but cannot be distinguished from reference type 2 (classical type 2) using the standard polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) with HaeIII digestion. Thus, we used MboI digestion in the PCR-RFLP analysis and re-examined the data from previous genotyping studies as well. This revealed that most strains reported as classical type 2 after 2010 in our studies were actually type 2j. The revised genotyping data showed that the type 2c and 2j strains have been spreading in recent years and were the most prevalent variants in Japan during the time-period of 2019 and 2020. We also analyzed the macrolide-resistance (MR) mutations in the 118 strains. MR mutations in the 23S rRNA gene were detected in 29 of these strains (29/118, 24.6%). The MR rate of type 1 lineage (14/29, 48.3%) was still higher than that of type 2 lineage (15/89, 16.9%); however, the MR rate of type 1 lineage was lower than that found in previous reports published in the 2010s, while that of type 2 lineage strains was slightly higher. Thus, there is a need for continuous surveillance of the p1 genotype and MR rate of M. pneumoniae clinical strains, to better understand the epidemiology and variant evolution of this pathogen, although M. pneumoniae pneumonia cases have decreased significantly since the COVID-19 pandemic.

Efficacy for diagnoses of scirrhous gastric cancer and safety of endoscopic ultrasound-guided fine-needle aspiration: A systematic review and meta-analysis.

Scirrhous gastric cancer (SGC) is diagnosed using endoscopy and/or biopsy; however, SGC diagnosis remains challenging owing to its special growth form and morphologic features. Hence, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is minimally invasive and has a high proportion of diagnostic tissue, may be an alternative investigative modality for patients with suspected SGC. This systematic review and meta-analysis aimed to identify and evaluate the evidence for the efficacy and safety of EUS-FNA in patients with suspected SGC. We conducted a systematic review using the PubMed (MEDLINE) and Ichushi-Web (NPO Japan Medical Abstracts Society) databases and included all entries in which SGC was evaluated using EUS-FNA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the databases' inception to October 10, 2022. The primary outcome was the proportion of SGC diagnosed using EUS-FNA. In addition, we analyzed the proportion of adverse events associated with EUS-FNA. The electronic search identified 1890 studies; overall, four studies met the selection criteria and reported data on EUS-FNA performed on 114 patients with suspected SGC. The overall diagnostic yield of EUS-FNA for SGC was 82.6% (95% confidence interval, 74.6-90.6%) and the statistical heterogeneity was 0% (I 2 = 0%), indicating a low heterogeneity. Furthermore, the EUS-FNA diagnostic proportion for SGC lymph node metastasis was 75-100%, indicating a high diagnostic performance. The adverse event rate of EUS-FNA was 0%. EUS-FNA may be an alternative investigation mode for SGC patients with negative esophagogastroduodenoscopy-biopsy results.

Duration of Initial Intensive Rivaroxaban Therapy for Patients With Venous Thromboembolism　- Subanalysis of the J'xactly Study.

Background: Rivaroxaban, a direct oral anticoagulant, is used as a first-line treatment to prevent venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). However, whether 21 days is optimal for the initial treatment duration has not been investigated. Methods and Results: In this subanalysis of the prospective multicenter observational J'xactly study, which included 1,039 Japanese patients with acute symptomatic/asymptomatic DVT/PE who were prescribed rivaroxaban, the VTE recurrence rate and incidence of bleeding complications were assessed in 667 patients who underwent intensive rivaroxaban treatment (15 mg, twice daily) for a short (1-8 days), intermediate (9-16), or standard (17-24) duration. The short treatment duration group showed a tendency for increased VTE recurrence/aggravation compared with the standard treatment duration group (6.10% vs. 2.60% per patient-year). The intermediate treatment duration group showed a higher incidence of bleeding events than the standard treatment duration group (9.34% vs. 2.16% per patient-year), without major differences in patient characteristics between the groups. Conclusions: In this subanalysis of the real-world observational J'xactly study of VTE treatment and prevention in Japanese patients with acute symptomatic/asymptomatic DVT/PE, the standard initial intensive rivaroxaban treatment duration (17-24 days) appeared to be safe and effective, providing important insights into the clinical outcomes of the initial rivaroxaban treatment duration in this population.

Steroid Pulse Therapy as a Treatment for Patients With COVID-19 Pneumonia at an Intensive Care Unit: A Single-Center Retrospective Observational Study.

BACKGROUND: Evidence supporting the use of steroid pulse therapy in severely ill patients with coronavirus disease 2019 (COVID-19) pneumonia is lacking. Few studies have evaluated the efficacy of high-dose (1000 mg/day) methylprednisolone (mPSL), which is commonly used in Japan. AIM: This study aimed to compare the clinical outcomes with and without steroid pulse therapy (mPSL 1000 or 500 mg/day for three days) in patients with COVID-19 pneumonia, admitted to an intensive care unit (ICU). METHODS: Study design was retrospective observational study. The inclusion criterion was severe to critically ill adult patients with COVID-19 pneumonia requiring ICU admission. The exclusion criteria were as follows: patients (1) with a "Do not attempt to resuscitate" order; (2) with a "Do not intubate" order; or (3) admitted to the ICU owing to other infectious diseases were excluded. Treatment strategy was as follows: Patients were divided into two groups: steroid pulse therapy (Group P) and steroids without pulse therapy (Group NP). Group P received mPSL 1000 or 500 mg/day on ICU days 1-3, and Group NP received dexamethasone 6.6 mg or mPSL 1 or 2 mg/kg/day. The primary outcome was 28-day mortality. RESULTS: We enrolled 82 patients. Out of 70 who met the inclusion criteria, 48 and 22 were included in Groups P and NP, respectively. No difference in 28-day survival was observed between the Groups P and NP (log-rank P=0.11). After adjusting for covariates (age, sex, interleukin-6 level, and acute physiology and chronic health evaluation II score on ICU admission) using a multivariate Cox proportional hazard model, treatment with steroid pulse therapy significantly improved 28-day mortality (hazard ratio, 0.14; 95% confidence interval, 0.02-0.86; P=0.03). CONCLUSION: Steroid pulse therapy may improve the 28-day mortality in patients with COVID-19 pneumonia in the ICU.

Relationship between baseline D-dimer and prognosis in Japanese patients with venous thromboembolism: Insights from the J'xactly study.

Background: D-dimer is a biomarker of fibrin production and degradation, and changes in D-dimer concentration suggest fibrin clot formation, which is associated with thromboembolism and hypercoagulable states. Thus, an elevated D-dimer concentration could be a useful prognostic predictor for patients with venous thromboembolism (VTE). Methods and results: In this subanalysis of the J'xactly study, a prospective multicenter study conducted in Japan, we examined the clinical outcomes of 949 patients with VTE stratified by baseline D-dimer concentration. The median D-dimer concentration was 7.6 µg/ml (low D-dimer group: <7.6 µg/ml [n = 473, 49.8%]; high D-dimer group: ≥7.6 µg/ml [n = 476, 50.2%]). The mean age of the patients was 68 years, and 386 patients (40.7%) were male. Compared with the low D-dimer group, the high D-dimer group had more frequent pulmonary embolism with or without deep vein thrombosis (DVT), proximal DVT, atrial fibrillation, or diabetes mellitus, and underwent intensive treatment with 30 mg/day rivaroxaban. The incidence of composite clinically relevant events (recurrence or exacerbation of symptomatic VTE, acute coronary syndrome [ACS], ischemic stroke, death from any cause, or major bleeding) was higher in the high D-dimer group than in the low D-dimer group (11.1% vs. 7.5% per patient-year; hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; p = 0.025). There was no significant difference between the high and low D-dimer groups in the incidence of VTE (2.8% vs. 2.5% per patient-year, respectively; p = 0.788), ACS (0.4% per patient-year vs. not observed, respectively; p = 0.078), or major bleeding (4.0% vs. 2.1% per patient-year, respectively; p = 0.087), but there was a significant difference in the incidence of ischemic stroke (1.0% per patient-year vs. not observed, respectively; p = 0.004). Conclusion: Elevated D-dimer concentration may be an important prognostic predictor in Japanese patients with VTE.Clinical Trial Registration: UMIN CTR, UMIN000025072 (https://www.umin.ac.jp/ctr/index.htm).

Effectiveness and safety of the direct oral anticoagulant in acute distal deep vein thrombosis: From the prospective multicenter observational study, J'xactly, in Japan.

OBJECTIVES: We assessed the effectiveness and safety of rivaroxaban in patients with isolated distal deep vein thrombosis (IDDVT). METHODS: Symptomatic venous thromboembolism (VTE) and major bleeding were assessed. RESULTS: Of 1016 patients with acute symptomatic/asymptomatic DVT and/or pulmonary embolism treated with rivaroxaban, 288 had IDDVT and 294 had proximal DVT (pDVT). The IDDVT group had fewer patients on the higher rivaroxaban dose (30 mg/day) (42.7% vs. 66.0%) and a shorter treatment duration (135.5 vs 369.5 days) than the pDVT group. VTE recurrence occurred in 14 and 11 patients with IDDVT and pDVT, respectively (2.89% vs. 2.29% per patient-year; p = 0.534). Major bleeding was less frequent in the IDDVT group (1.55% vs. 4.53% per patient-year; p = 0.044). Comparable effectiveness and safety were observed with 15 and 30 mg/day rivaroxaban in the IDDVT group. CONCLUSIONS: Short-term, low-dose rivaroxaban seems safe and effective for IDDVT treatment.

Effectiveness and safety of rivaroxaban in patients with venous thromboembolism and active cancer: A subanalysis of the J'xactly study.

BACKGROUND: Data on the effectiveness and safety of rivaroxaban for the treatment of patients with venous thromboembolism (VTE) and active cancer are limited in the Japanese real-world setting. METHODS: In this subanalysis of the J'xactly study, which was a multicenter, prospective, observational study, we evaluated the effectiveness and safety of rivaroxaban in patients with acute VTE and active cancer (n = 193) versus those without active cancer (n = 823). RESULTS: Compared with patients without active cancer, those with active cancer demonstrated a significantly different age distribution, with fewer aged <65 and ≥75 years; a lower proportion of women; a lower mean body mass index; and a lower proportion of physical inactivity, injury, thrombophilia, and heart failure. There was no difference in the initial dose distribution of rivaroxaban between patients with and without active cancer. The incidences of recurrence or aggravation of symptomatic VTE and major bleeding were not significantly different [VTE: 1.44 % vs. 2.80 % per patient-year, hazard ratio (HR) 0.50, 95 % confidence interval (CI) 0.18-1.39, p = 0.172; major bleeding: 4.49 % vs. 2.55 % per patient-year, HR 1.80, 95 % CI 0.82-3.95, p = 0.137]. Approximately 10 % of patients with active cancer died at 6 months, with a significantly higher cumulative all-cause mortality rate than those without active cancer (23.29 % vs. 2.03 % per patient-year, HR 11.31, 95 % CI 7.30-17.53, p < 0.001). CONCLUSIONS: In patients with VTE and active cancer, rivaroxaban showed acceptable effectiveness, although clinically significant bleeding remains a concern. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000025072.

A first-in-human study of the anti-inflammatory profibrinolytic TMS-007, an SMTP family triprenyl phenol.

AIMS: TMS-007, an SMTP family member, modulates plasminogen conformation and enhances plasminogen-fibrin binding, leading to promotion of endogenous fibrinolysis. Its anti-inflammatory action, mediated by soluble epoxide hydrolase inhibition, may contribute to its efficacy. Evidence suggests that TMS-007 can effectively treat experimental thrombotic and embolic strokes with a wide time window, while reducing haemorrhagic transformation. We aim to evaluate the safety, pharmacokinetics and pharmacodynamics of TMS-007 in healthy volunteers. METHODS: This was a randomized, placebo-controlled, double blind, dose-escalation study, administered as a single intravenous infusion of TMS-007 in cohorts of healthy male Japanese subjects. Six cohorts were planned, but only five were completed. In each cohort (n = 8), individuals were randomized to receive one of five doses of TMS-007 (3, 15, 60, 180 or 360 mg; n = 6) or placebo (n = 2). RESULTS: TMS-007 was generally well tolerated, and no serious adverse events were attributed to the drug. A linear dose-dependency was observed for plasma TMS-007 levels. No symptoms of bleeding were observed on brain MRI analysis, and no bleeding-related responses were found on laboratory testing. The plasma levels of the coagulation factor fibrinogen and the anti-fibrinolysis factor α2 -antiplasmin levels were unchanged after TMS-007 dosing. A slight increase in the plasma level of plasmin-α2 -antiplasmin complex, an index of plasmin formation, was observed in the TMS-007 group in cohort 2. CONCLUSIONS: TMS-007 is generally well tolerated and exhibits favourable pharmacokinetic profiles that warrant further clinical development.

Efficacy of Remifentanil in Patients Undergoing Cardiac Surgery: A Systematic Review and Network Meta-Analysis.

Remifentanil, characterized by its ultra-short action duration and nonorgan-dependent metabolism, is applied in postcardiac surgery settings worldwide. While previous studies have compared its efficacy with that of other opioids, it has never been compared to a single specific opioid. Here, we evaluated whether remifentanil shortens mechanical ventilation (MV) times in patients after cardiac surgery. We identified randomized controlled trials that compared various opioids in adults (≥18 years) admitted to the intensive care unit after cardiac surgery. The primary outcome was the duration of MV, expressed as the mean difference (MD) in minutes, with a 95% confidence interval (CI). A 60-min reduction was considered significant based on prior research. Data were sourced from MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platforms Search Portal, and ClinicalTrials.gov, and a frequentist network meta-analysis was conducted. The eight identified studies indicate no differences in the duration of MV between remifentanil and fentanyl (MD 0.09 min; 95%CI -36.89-37.08), morphine (MD -19 min; 95%CI -55.86-16.21), or sufentanil (MD -2.44 min; 95%CI -67.52-62.55). Our study revealed that remifentanil did not reduce MV times in patients after cardiac surgery. The study protocol was registered with the Open Science Forum (https://osf.io/) (DOI 10.17605/OSF.IO/YAHW2).

Factors Associated With Time to Achieve Physical Functional Recovery in Patients With Severe Stoke After Inpatient Rehabilitation: A Retrospective Nationwide Cohort Study in Japan.

Objective: To describe characteristics of patient with severe stroke (FIM motor score [FIM motor] 20-49 at admission) and examine association between pre-specified factors (age, sex, modified Rankin Scale before stroke onset, body mass index, FIM motor, and FIM cognitive) and time to achieve FIM motor ≥70, that is, self-independent level. Design: Retrospective cohort study using a large database in Japan. Setting: Rehabilitation wards. Participants: Patients with severe stroke (N=1422) who received inpatient rehabilitation were included (median age: 76 years; interquartile range [IQR]: 68.0-84.0). A total of 54.6% were men, and 65.8% were ischemic stroke. Interventions: Not applicable. Main Outcome Measures: Time to achieve FIM motor ≥70. Results: After inpatient rehabilitation, 40.4% (N=575) achieved FIM motor ≥70 (admission FIM motor 20-29, 30-39 and 40-49: 18.6%, 33.6%, and 47.8%, respectively). Patients who achieved FIM motor ≥70 stayed median 81.0 days [IQR, 51.0-120.0]) and received median: 6.94 units per day [IQR, 5.48-7.78], 1 unit=20 minutes). Adjusted Fine-Gray regression revealed that shorter time to achieve FIM motor ≥70 was associated with higher admission FIM motor (hazard ratio [HR] 2.87 [95% confidence interval [CI] 2.27-3.62]: 20-29 vs 40-49), higher admission FIM cognitive (HR 1.81 [95% CI: 1.39-2.35]: 5-14 vs 25-35), and younger (HR 3.20 [95% CI: 2.32-4.42]: ≥85 years vs 20-69 years). Conclusions: Most patients with severe stroke did not achieve FIM motor ≥70 after inpatient rehabilitation. Older patients and patients with lower admission FIM motor require more attention. They should be prioritized for state-of-the-art rehabilitation therapy.

Perspectives on Collaboration between Physicians and Nurse Practitioners in Japan: A Cross-Sectional Study.

BACKGROUND: Nurse practitioners (NPs) are known as effective healthcare providers worldwide. In Japan, nurse practitioner adoption is considered to be in a shaky period. Although nurse practitioners were introduced approximately 10 years ago at the initiative of educational institutions in Japan, the full extent of this trend is not known. Therefore, we have clarified the whole picture of nurse practitioners from two directions: the perception of nurse practitioners in Japan and the perception of physicians who work with nurse practitioners. This will inform discussions regarding the recruitment of nurse practitioners at the national level in Japan. METHODS: From 18 June to 24 July 2021, we administered a nationwide cross-sectional survey of NPs and physicians working in the same clinical settings as NPs in Japan. The domains of the survey included "scope and content of work", "perceptions of NPs' clinical practice", and "individual clinical practice characteristics". The survey was distributed and collected digitally. RESULTS: The total number of respondents to the survey was 281, including 169 NPs and 112 physicians; the percentage of NPs who responded was 50.5%. The number of valid responses was 164 NPs and 111 physicians, for a total of 275 respondents. Approximately 60% of NPs are concentrated in Tokyo, the capital of Japan, and the three prefectures adjacent to Tokyo. They also worked fewer hours per week, cared for fewer patients per day, and earned less money than physicians. More physicians than NPs indicated that "more NPs would improve the quality of care". A total of 90.1% of physicians and 82.3% of NPs agreed that "Nurse practitioners should practice to the full extent of their education and training," and 73.9% of physicians and 81.7% of NPs agreed that "Nurse practitioners' scope of practice should be uniformly defined at a national level". CONCLUSIONS: This study clarified the present working conditions of NPs from NPs' and physicians' perspectives in Japanese contexts. Japanese NPs may be able to work effectively in collaboration with physicians. Therefore, the implementation of NPs in Japanese medical conditions should be discussed further for better healthcare.

Rivaroxaban Treatment for Patients With Unprovoked or Provoked Venous Thromboembolism　- Subanalysis of the J'xactly Study.

Background: The efficacy and safety of direct oral anticoagulants (DOACs) in patients with unprovoked venous thromboembolism (VTE) remain unclear. Methods and Results: In this subanalysis of the J'xactly study, a multicenter prospective observational study, we evaluated the safety and effectiveness of rivaroxaban in patients with acute VTE according to unprovoked (n=388) or provoked (n=557) VTE status. Median follow-up was 21.2 months. Compared with patients in the provoked group, patients in the unprovoked group were younger, less likely to be female, and had higher body weight. The incidence of symptomatic VTE recurrence was significantly higher in the unprovoked than provoked VTE group (3.54% vs. 1.77% per patient-year; P=0.032). There was no significant difference in the incidence of major bleeding events between rivaroxaban-treated patients with unprovoked and provoked VTE (2.31% vs. 3.75% per patient-year; P=0.289). Although the proportion of patients with a body mass index (BMI) ≥25 kg/m2 who were non-users of antiplatelet agents was higher in the unprovoked VTE group, there was no interaction effect (BMI: 4.58% vs. 1.55% per patient-year [P=0.040; P for interaction=0.361]; concomitant antiplatelet agent non-users: 3.65% vs. 1.72% per patient-year [P=0.028; P for interaction=0.627]). Conclusions: This subanalysis suggests the safety and effectiveness of rivaroxaban in patients with unprovoked VTE. In such patients, DOAC discontinuation should be considered carefully, particularly in those not using antiplatelet agents and those with a high BMI.

Clinical Outcome After Discontinuation of Anticoagulation Therapy in Japanese Patients With Venous Thromboembolism　- Insights From the J'xactly Study.

Background: Rivaroxaban, a direct oral anticoagulant, is used as first-line treatment to prevent venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). However, the frequency of rivaroxaban discontinuation and the subsequent clinical outcomes remain unclear. Methods and Results: The study was a subanalysis of the prospective, multicenter, observational J'xactly study, conducted in Japan, and included patients who underwent anticoagulant discontinuation without major bleeding and recurrent VTE. The modified intention-to-treat population (n=1,016) included 579 patients (57%) who underwent anticoagulant discontinuation during a mean follow-up period of 20.2 months (mean [±SD] anticoagulation period 6.9±6.2 months). Patients were divided into 3 groups: those with active cancer, those without active cancer and a transient risk factor for VTE, and those without active cancer or a transient risk factor and/or with previous VTE (unprovoked group). After discontinuation, VTE recurrence occurred in 4.1% of patients, with an annual incidence of 4.6%/year and an increased tendency in the unprovoked group; major bleeding occurred in 8 patients (1.4%; annual incidence 1.1%/year), of whom half were in the cancer group. Conclusions: This analysis of a real-world observational study provides data on VTE recurrence after rivaroxaban discontinuation, which will facilitate anticoagulant discontinuation according to individual risk-benefit considerations.