Systematic review and meta-analysis for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA). METHODS: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, 2 independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. RESULTS: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to csDMARD. Rituximab with and without concomitant csDMARDs showed similar efficacy to other bDMARDs in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. CONCLUSION: This systematic review provides latest evidence for the 2024 update of the JCR CPG for RA management.

Comparing outcomes of out-of-hospital cardiac arrest patients with initial shockable rhythm in Singapore and Osaka using population-based databases.

BACKGROUND: Previous research indicated outcomes among refractory out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm were different in Singapore and Osaka, Japan, possibly due to the differences in access to extracorporeal cardiopulmonary resuscitation. However, this previous study had a risk of selection bias. To address this concern, this study aimed to evaluate the outcomes between Singapore and Osaka for OHCA patients with initial shockable rhythm using only population-based databases. METHODS: This was a secondary analysis of two OHCA population-based databases in Osaka and Singapore, including adult OHCA patients with initial shockable rhythm. A machine-learning-based prediction model was derived from the Osaka data (n = 3088) and applied to the PAROS-SG data (n = 2905). We calculated the observed-expected ratio (OE ratio) for good neurological outcomes observed in Singapore and the expected derived from the data in Osaka by dividing subgroups with or without prehospital ROSC. RESULTS: The one-month good neurological outcomes in Osaka and Singapore among patients with prehospital ROSC were 70% (791/1,125) and 57% (440/773), and among patients without prehospital ROSC were 10% (196/1963) and 2.8% (60/2,132). After adjusting patient characteristics, the outcome in Singapore was slightly better than expected from Osaka in patients with ROSC (OE ratio, 1.067 [95%CI 1.012 to 1.125]), conversely, it was worse than expected in patients without prehospital ROSC (OE ratio, 0.238 [95%CI 0.173 to 0.294]). CONCLUSION: This study showed the outcomes of OHCA patients without prehospital ROSC in Singapore were worse than expected derived from Osaka data even using population-based databases. (249/250 words).

Outcome assessment for out-of-hospital cardiac arrest patients in Singapore and Japan with initial shockable rhythm.

BACKGROUND: Singapore and Osaka in Japan have comparable population sizes and prehospital management; however, the frequency of ECPR differs greatly for out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm. Given this disparity, we hypothesized that the outcomes among the OHCA patients with initial shockable rhythm in Singapore were different from those in Osaka. The aim of this study was to evaluate the outcomes of OHCA patients with initial shockable rhythm in Singapore compared to the expected outcomes derived from Osaka data using machine learning-based prediction models. METHODS: This was a secondary analysis of two OHCA databases: the Singapore PAROS database (SG-PAROS) and the Osaka-CRITICAL database from Osaka, Japan. This study included adult (18-74 years) OHCA patients with initial shockable rhythm. A machine learning-based prediction model was derived and validated using data from the Osaka-CRITICAL database (derivation data 2012-2017, validation data 2018-2019), and applied to the SG-PAROS database (2010-2016 data), to predict the risk-adjusted probability of favorable neurological outcomes. The observed and expected outcomes were compared using the observed-expected ratio (OE ratio) with 95% confidence intervals (CI). RESULTS: From the SG-PAROS database, 1,789 patients were included in the analysis. For OHCA patients who achieved return of spontaneous circulation (ROSC) on hospital arrival, the observed favorable neurological outcome was at the same level as expected (OE ratio: 0.905 [95%CI: 0.784-1.036]). On the other hand, for those who had continued cardiac arrest on hospital arrival, the outcomes were lower than expected (shockable rhythm on hospital arrival, OE ratio: 0.369 [95%CI: 0.258-0.499], and nonshockable rhythm, OE ratio: 0.137 [95%CI: 0.065-0.235]). CONCLUSION: This observational study found that the outcomes for patients with initial shockable rhythm but who did not obtain ROSC on hospital arrival in Singapore were lower than expected from Osaka. We hypothesize this is mainly due to differences in the use of ECPR.

In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score. METHODS: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model. RESULTS: Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls. CONCLUSION: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.

Systematic review and meta-analysis for 2023 clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis.

OBJECTIVES: The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis. METHODS: PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach. RESULTS: For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively. CONCLUSIONS: This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.

Clinical Phenotyping of Out-of-Hospital Cardiac Arrest Patients With Shockable Rhythm　- Machine Learning-Based Unsupervised Cluster Analysis.

BACKGROUND: The hypothesis of this study is that latent class analysis could identify the subphenotypes of out-of-hospital cardiac arrest (OHCA) patients associated with the outcomes and allow us to explore heterogeneity in the effects of extracorporeal cardiopulmonary resuscitation (ECPR).Methods and Results:This study was a retrospective analysis of a multicenter prospective observational study (CRITICAL study) of OHCA patients. It included adult OHCA patients with initial shockable rhythm. Patients from 2012 to 2016 (development dataset) were included in the latent class analysis, and those from 2017 (validation dataset) were included for evaluation. The association between subphenotypes and outcomes was investigated. Further, the heterogeneity of the association between ECPR implementation and outcomes was explored. In the study results, a total of 920 patients were included for latent class analysis. Three subphenotypes (Groups 1, 2, and 3) were identified, mainly characterized by the distribution of partial pressure of O2(PO2), partial pressure of CO2(PCO2) value of blood gas assessment, cardiac rhythm on hospital arrival, and estimated glomerular filtration rate. The 30-day survival outcomes were varied across the groups: 15.7% in Group 1; 30.7% in Group 2; and 85.9% in Group 3. Further, the association between ECPR and 30-day survival outcomes by subphenotype groups in the development dataset was as varied. These results were validated using the validation dataset. CONCLUSIONS: The latent class analysis identified 3 subphenotypes with different survival outcomes and potential heterogeneity in the effects of ECPR.

Carnitine supplements for people with chronic kidney disease requiring dialysis.

BACKGROUND: Carnitine deficiency is common in patients with chronic kidney disease (CKD) who require dialysis. Several clinical studies have suggested that carnitine supplementation is beneficial for dialysis-related symptoms. However, the clinical effectiveness and potential adverse effects of carnitine supplementation in dialysis patients have not been determined. OBJECTIVES: This review aimed to evaluate the effectiveness and safety of carnitine supplementation for the treatment of dialysis-related complications in CKD patients requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 August 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth, or other predictable methods) that compared carnitine supplements with placebo or standard care in people with CKD requiring dialysis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted study data and assessed study quality. We used a random-effects model to perform a quantitative synthesis of the data.  We used the I² statistic to measure heterogeneity amongst the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with 95% confidence intervals (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. MAIN RESULTS: We included 52 studies (47 parallel RCTs and five cross-over RCTs) (3398 randomised participants). All studies compared L-carnitine with a placebo, other treatment, or no treatment. Standard care was continued as co-interventions in each group. Most studies were judged to have an unclear or high risk of bias. L-carnitine may have little or no effect on the quality of life (QoL) SF-36 physical component score (PCS) (4 studies, 134 participants: SMD 0.57, 95% CI -0.15 to 1.28; I² = 73%; low certainty of evidence), and the total QoL score (Kidney Disease Quality of Life (KDQOL), VAS (general well-being), or PedsQL) (3 studies, 230 participants: SMD -0.02, 95% CI -0.29 to 0.25; I² = 0%; low certainty of evidence). L-carnitine may improve SF-36 mental component score (MCS) (4 studies, 134 participants: SMD 0.70, 95% CI 0.22 to 1.18; I² = 42%; low certainty of evidence). L-carnitine may have little or no effect on fatigue score (2 studies, 353 participants: SMD 0.01, 95% CI -0.20 to 0.23; I² = 0%; low certainty of evidence), adverse events (12 studies, 1041 participants: RR, 1.14, 95% CI 0.86 to 1.51; I² = 0%; low certainty of evidence), muscle cramps (2 studies, 102 participants: RR, 0.44, 95% CI 0.18 to 1.09; I² = 23%; low certainty of evidence), and intradialytic hypotension (3 studies, 128 participants: RR, 0.76, 95% CI 0.34 to 1.69; I² = 0%; low certainty of evidence). L-carnitine may improve haemoglobin levels (26 studies, 1795 participants: MD 0.46 g/dL, 95% CI 0.18 to 0.74; I² = 86%; low certainty of evidence) and haematocrit values (14 studies, 950 participants: MD 1.78%, 95% CI 0.38 to 3.18; I² = 84%; low certainty of evidence). AUTHORS' CONCLUSIONS: The available evidence does not currently support the use of carnitine supplementation in the treatment of dialysis-related carnitine deficiency. Although carnitine supplementation may slightly improve anaemia-related markers, carnitine supplementation makes little or no difference to adverse events. However, these conclusions are based on limited data and, therefore, should be interpreted with caution.

Early prognostic impact of serum sodium level among out-of-hospital cardiac arrest patients: a nationwide multicentre observational study in Japan (the JAAM-OHCA registry).

Dysnatremia is an electrolytic disorder commonly associated with mortality in various diseases. However, little is known about dysnatremia in out-of-hospital cardiac arrest (OHCA) cases. Here, we investigated the association between serum sodium level on hospital arrival and neurological outcomes after OHCA. This nationwide hospital-based observational study (The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry) enrolled patients with OHCA between 2014 and 2017. We included adult patients aged ≥ 18 years with non-traumatic OHCA who achieved return of spontaneous circulation (ROSC) and whose serum sodium level on hospital arrival was available. Based on the serum sodium level, patients were divided into three levels: hyponatremia (Na < 135 mEq/L), normal sodium level (Na ≥ 135 or ≤ 145 mEq/L), and hypernatremia (Na > 145 mEq/L). The primary outcome was 1-month survival with favourable neurological outcomes. Altogether, 34 754 patients with OHCA were documented, and 5160 patients with non-traumatic OHCA and who achieved ROSC were eligible for our analyses. The proportion of favourable neurological outcomes was highest in patients with normal sodium levels at 17.6% (677/3854), followed by patients with hyponatremia at 8.2% (57/696) and patients with hypernatremia at 5.7% (35/610). Moreover, hyponatremia and hypernatremia were associated with a decreased probability of favourable neurological outcomes compared with normal sodium level (vs. hyponatremia, adjusted odds ratio [AOR] 0.97, 95% confidence interval [CI] 0.95-0.99; vs. hypernatremia, AOR 0.96, 95% CI 0.94-0.98). Hypo- and hypernatremia on hospital arrival were associated with a decreased probability of favourable neurological outcomes in patients with non-traumatic OHCA who achieved ROSC.

Association between initial body temperature on hospital arrival and neurological outcome among patients with out-of-hospital cardiac arrest: a multicenter cohort study (the CRITICAL study in Osaka, Japan).

BACKGROUND: The association between spontaneous initial body temperature on hospital arrival and neurological outcomes has not been sufficiently studied in patients after out-of-hospital cardiac arrest (OHCA). METHODS: From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all patients with OHCA of medical origin aged > 18 years for whom resuscitation was attempted and who were transported to participating hospitals between 2012 and 2019. We excluded patients who were not witnessed by bystanders and treated by a doctor car or helicopter, which is a car/helicopter with a physician. The patients were categorized into three groups according to their temperature on hospital arrival: ≤35.9 °C, 36.0-36.9 °C (normothermia), and ≥ 37.0 °C. The primary outcome was 1-month survival, with a cerebral performance category of 1 or 2. Multivariable logistic regression analyses were performed to evaluate the association between temperature and outcomes (normothermia was used as the reference). We also assessed this association using cubic spline regression analysis. RESULTS: Of the 18,379 patients in our database, 5014 witnessed adult OHCA patients of medical origin from 16 hospitals were included. When analyzing 3318 patients, OHCA patients with an initial body temperature of ≥37.0 °C upon hospital arrival were associated with decreased favorable neurological outcomes (6.6% [19/286] odds ratio, 0.51; 95% confidence interval, 0.27-0.95) compared to patients with normothermia (16.4% [180/1100]), whereas those with an initial body temperature of ≤35.9 °C were not associated with decreased favorable neurological outcomes (11.1% [214/1932]; odds ratio, 0.78; 95% confidence interval, 0.56-1.07). The cubic regression splines demonstrated that a higher body temperature on arrival was associated with decreased favorable neurological outcomes, and a lower body temperature was not associated with decreased favorable neurological outcomes. CONCLUSIONS: In adult patients with OHCA of medical origin, a higher body temperature on arrival was associated with decreased favorable neurologic outcomes.

Trends in In-Hospital Advanced Management and Survival of Out-of-Hospital Cardiac Arrest Among Adults From 2013 to 2017　- A Multicenter, Prospective Registry in Osaka, Japan.

BACKGROUND: The aim of our study was to investigate in detail the temporal trends in in-hospital characteristics, actual management, and survival, including neurological status, among adult out-of-hospital cardiac arrest (OHCA) patients in recent years.Methods and Results:From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all OHCA patients aged ≥18 years for whom resuscitation was attempted, and who were transported to participating hospitals between the years 2013 and 2017. The primary outcome measure was 1-month survival with favorable neurological outcome after OHCA. Temporal trends in in-hospital management and favorable neurological outcome among adult OHCA patients were assessed. Of the 11,924 patients in the database, we included a total of 10,228 adult patients from 16 hospitals. As for in-hospital advanced treatments, extracorporeal cardiopulmonary resuscitation (ECPR) use increased from 2.4% in 2013 to 4.3% in 2017 (P for trend <0.001). However, the proportion of adult OHCA patients with favorable neurological outcome did not change during the study period (from 5.7% in 2013 to 4.4% in 2017, adjusted odds ratio (OR) for 1-year increment: 0.98 (95% confidence interval: 0.94-1.23)). CONCLUSIONS: In this target population, in-hospital management such as ECPR increased slightly between 2013 and 2017, but 1-month survival with favorable neurological outcome after adult OHCA did not improve significantly.

Poor Long-Term Survival of Out-of-Hospital Cardiac Arrest in Children.

The effect of post-cardiac arrest care in children with out-of-hospital cardiac arrest (OHCA) has not been adequately established, and the long-term outcome after pediatric OHCA has not been sufficiently investigated. We describe here detailed in-hospital characteristics, actual management, and survival, including neurological status, 90 days after OHCA occurrence in children with OHCA transported to critical care medical centers (CCMCs).We analyzed the database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study, which is a multicenter, prospective observational data registry designed to accumulate both pre- and in-hospital data on OHCA treatments. We enrolled all consecutive pediatric patients aged <18 years who had an OHCA and for whom resuscitation was attempted and who were transported to CCMCs between 2012 and 2016.A total of 263 pediatric patients with OHCA were enrolled. The average age of the patients was 6.3 years, 38.0% were aged < 1 year, and 60.8% were male. After hospital arrival, 4.9% of these pediatric patients received defibrillation; 1.9%, extracorporeal life support; 6.5%, target temperature management; and 88.2% adrenaline administration. The proportions of patients with 90-day survival and a pediatric cerebral performance category (PCPC) score of 1 or 2 were 6.1% and 1.9%, respectively. The proportion of patients with a PCPC score of 1 or 2 at 90 days after OHCA occurrence did not significantly improve during the study period.The proportion of pediatric patients with a 90-day PCPC score of 1 or 2 transported to CCMCs was extremely low, and no significant improvements were observed during the study period.

Association of pre-hospital tracheal intubation with outcomes after out-of-hospital cardiac arrest by drowning comparing to supraglottic airway device: A nationwide propensity score-matched cohort study.

AIM OF THE STUDY: This study aimed to compare the survival outcomes of adult patients with out-of-hospital cardiac arrest (OHCA) by drowning who were treated with either endotracheal intubation (ETI) or a supraglottic airway (SGA) device. METHODS: We compared the outcomes of patients with OHCA by drowning according to airway management using a Japanese nationwide population-based registry (All-Japan Utstein Registry). Adult patients with OHCA treated in 2014-2020 with advanced airway management (ETI or SGA) were included. Patients who received ETI during cardiopulmonary resuscitation were matched with those treated with SGA based on propensity scores in a 1:1 ratio with a 0.2 calliper width. The outcome measures were the return of spontaneous circulation (ROSC), survival at one month, and favourable neurological outcomes defined as a Cerebral Performance Category Scale score of 1 or 2. RESULTS: Of the 11,703 eligible patients, 4,467 (38.2%) and 7,236 (61.8%) underwent ETI and SGA, respectively. A total of 3,566 patients in each cohort were matched. The ROSC rate was higher in those treated with ETI versus SGA (207/3,566 [5.8%] versus 167/3,566 [4.7%], respectively; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.02-1.55). There was no intergroup difference in one-month survival or favourable neurological outcome (32/3566 [0.90%] versus 34/3566 [0.95%]; odds ratio, 0.94; 95% CI, 0.58-1.53; and 9/3566 [0.25%] versus 8/3566 [0.22%]; odds ratio, 1.13; 95% CI, 0.43-2.92), respectively. CONCLUSIONS: In this propensity score-matched study of adult OHCA by drowning, ETI compared to SGA was associated with ROSC but not associated with survival and favourable neurological outcomes at one month.

Early prediction for massive fresh frozen plasma transfusion based on fibrinogen/fibrin degradation products and D-dimer in patients with blunt trauma: a single-center, retrospective cohort study.

PURPOSE: This study aimed to examine the association of fibrinogen/fibrin degradation product (FDP) values in comparison with D-dimer and fibrinogen (Fib) values and the need for massive fresh frozen plasma (FFP) transfusion in patients with blunt trauma. METHODS: This retrospective study included patients with blunt trauma aged ≥ 18 years who were transported directly to the tertiary care hospital between April, 2012, and March, 2021. Massive FFP transfusion was defined as a composite outcome of at least 10 units of FFP or death for any cause except for cerebral herniation, within 24 h after hospital arrival. We evaluated the diagnostic accuracy of predicting the need for massive FFP transfusions using FDP, D-dimer, and Fib levels at the time of hospital arrival. RESULTS: A total of 2160 patients were eligible for the analysis, of which 167 fulfilled the criteria for the composite outcome. The area under the curve and 95% confidence interval for FDP, D-dimer, and Fib levels were 0.886 (0.865-0.906), 0.885 (0.865-0.906), and 0.771 (0.731-0.810), respectively. When the cutoff values of FDP and D-dimer were set at 90 µg/mL and 45 µg/mL, the sensitivity values were 77% and 78%, the positive predictive values were 28% and 27%, and the negative predictive values were both 98%, respectively. In contrast, the sensitivity of Fib was low regardless of the cutoff value. CONCLUSION: FDP and D-dimer levels at the time of hospital arrival showed a higher predictive accuracy for the need for massive FFP transfusion than Fib.

Eating behaviors and incidence of type 2 diabetes in Japanese people: The population-based Panasonic cohort study 15.

AIM/INTRODUCTION: This historical cohort study sought to research the relationship between eating behaviors and the incidence of type 2 diabetes in a large, long-term cohort of Japanese subjects. MATERIALS AND METHODS: Panasonic Corporation employees who had no history of diabetes and attended yearly health surveys between 2008 and 2018 were included in this study. The main outcome measure was diabetes onset. RESULTS: This study included 128,594 participants and 6,729 participants who developed type 2 diabetes in the study period. Skipping breakfast, fast eating, snacking after dinner, and eating meals before sleeping were linked with the risk of the incidence of type 2 diabetes. In individuals with a BMI < 25 kg/m2, fast eating (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.37-1.90), and eating meals before sleeping (HR: 1.09, 95% CI: 1.02-1.17) were likewise associated with an increased risk of incident type 2 diabetes. Nevertheless, fast eating (HR: 1.08, 95% CI: 0.89-1.30) and meals before sleeping (HR: 0.94, 95% CI: 0.88-1.01) were not related to the occurrence of type 2 diabetes in individuals with a BMI ≥25 kg/m2 (P value for interaction = 0.0007 [fast eating] and 0.007 [meals before sleeping], respectively). No significant interaction effect between sex and eating behavior was found. CONCLUSIONS: With respect to Japanese people, especially in people with a BMI < 25 kg/m2, eating behaviors may be a risk factor for the occurrence of type 2 diabetes.

The transition of metabolic phenotypes and cardiovascular events: Panasonic cohort study 16.

OBJECTIVE: The study objective was to investigate whether changes in metabolic phenotype affect the risk of cardiovascular events. METHODS: All 117,589 participants were included in this retrospective cohort study. The metabolic phenotypes of the participants were assessed at two points (the second evaluation was set 2 years after the first evaluation), and the incidence rate of cardiovascular events was observed for 11 years. The main outcome was 3-point major adverse cardiac events (MACE), which comprises cardiovascular death, nonfatal coronary artery disease, and nonfatal stroke incidence. RESULTS: Of the participants, 2748 (2.3%) cases of 3-point MACE were identified during follow-up. The stable metabolically healthy obesity group had a higher risk of 3-point MACE than those with stable metabolically healthy nonobesity (MHNO). Additionally, the change from metabolically healthy obesity to MHNO for 2 years decreased the risk of 3-point MACE (hazard ratio [HR], 1.12: 95% CI: 0.84-1.47) to the same level as stable MHNO. However, the change from metabolically abnormal nonobesity and metabolically abnormal obesity to MHNO for 2 years maintained a higher risk of 3-point MACE (HR, 1.66 [95% CI: 1.36-2.01]; HR, 1.91 [95% CI: 1.22-2.81]) than those with stable MHNO. CONCLUSIONS: Change in metabolic phenotype is associated with incident 3-point MACE.

Overview and future prospects of out-of-hospital cardiac arrest registries in Japan.

Aim: Out-of-hospital cardiac arrest (OHCA) is a life-threatening emergency with high mortality. The "chain of survival" is critical to improving patient outcomes. To develop and enhance this chain of survival, measuring and monitoring the resuscitation processes and outcomes are essential for quality assurance. In Japan, several OHCA registries have successfully been implemented at both local and national levels. We aimed to review and summarise the conception, strengths, and challenges of OHCA registries in Japan. Method and results: The following representing registries in Japan were reviewed: the All-Japan Utstein registry, the Utstein Osaka Project/the Osaka-CRITICAL study, the SOS-KANTO study, the JAAM-OHCA study, and the SAVE-J II study. The All-Japan Utstein registry, operated by the Fire and Disaster Management Agency of Japan and one of the largest nationwide population-based registries in the world, collects data concerning all patients with OHCA in Japan, excluding in-hospital data. Other research- and hospital-based registries collect detailed out-of-hospital and in-hospital data. The Osaka-CRITICAL study and the SOS-KANTO study are organized at regional levels, and hospitals in the Osaka prefecture and in the Kanto area participate in these registries. The JAAM-OHCA study is managed by the Japanese Association of Acute Medicine and includes 107 hospitals throughout Japan. The Save-J II study focuses on patients with OHCA treated with extracorporeal cardiopulmonary resuscitation. Conclusion: Each OHCA registry has its own philosophy, strengths, perspectives, and challenges; however, all have been successful in contributing to the improvement of emergency medical service (EMS) systems through the quality improvement process. These registries are expected to be further utilized to enhance EMS systems and improve outcomes for patients with OHCA, while also contributing to the field of resuscitation science.

Clinical profile of patients with diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome in Japan: a multicenter retrospective cohort study.

INTRODUCTION: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated. METHODS: A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes. RESULTS: A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10-26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups. CONCLUSIONS: The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population. TRIAL REGISTRATION: This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016).

Non-linear association between the time required to reaching temperature targets and the neurological outcome in patients undergoing targeted temperature management after out-of-hospital cardiac arrest: Observational multicentre cohort study.

Purpose: We evaluated associations between outcomes and time to achieving temperature targets during targeted temperature management of out-of-hospital cardiac arrest. Methods: Using Comprehensive Registry of Intensive Care for out-of-hospital cardiac arrest Survival (CRITICAL) study, we enrolled all patients transported to participating hospitals from 1 July 2012 through 31 December 2017 aged ≥ 18 years with out-of-hospital cardiac arrest of cardiac aetiology and who received targeted temperature management in Osaka, Japan. Primary outcome was Cerebral Performance Category scale of 1 or 2 one month after cardiac arrest, designated as "one-month favourable neurological outcome". Non-linear multivariable logistic regression analyses assessed the primary outcome based on time to reaching temperature targets. In patients subdivided into quintiles based on time to achieving temperature targets, multivariable logistic regression calculated adjusted odds ratios and 95% confidence intervals. Results: We analysed 473 patients. In non-linear multivariable logistic regression analysis, p value for non-linearity was < 0.01. In the first quintile (< 26.7 minutes), second quintile (26.8-89.9 minutes), third quintile (90.0-175.1 minutes), fourth quintile (175.2-352.1 minutes), and fifth quintile (≥ 352.2 minutes), one-month favourable neurological outcome was 32.6% (31/95), 40.0% (36/90), 53.5% (53/99), 57.4% (54/94), and 37.9% (36/95), respectively. Adjusted odds ratios with 95% confidence intervals for one-month favourable neurological outcome in the first, second, third, and fifth quintiles compared with the fourth quintile were 0.38 (0.20 to 0.72), 0.43 (0.23 to 0.81), 0.77 (0.41 to 1.44), and 0.46 (0.25 to 0.87), respectively. Conclusion: Non-linear multivariable logistic regression analysis could clearly describe the association between neurological outcome in patients with out-of-hospital cardiac arrest and the time from the introduction of targeted temperature management to reaching the temperature targets.