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In open-label trials, the details of the adjudicators are essential to evaluate the risk of detection bias. We aimed to describe how the adjudicators of progression-free survival (PFS) and objective response rate (ORR) have been reported in open-label trials of anticancer drugs.A literature search was conducted using MEDLINE via PubMed. We included open-label, parallel-group superiority randomized trials that investigated the PFS and ORR of anticancer drugs for solid tumors. After screening based on the titles and abstracts, 200 articles were randomly selected from 2017 to 2021. The researchers independently checked the eligibility and collected the adjudicators' information in the protocol, registry, and original article.One hundred fifty five studies reported the PFS and ORR. Approximately half of the studies did not report adjudicators (47.7% in PFS and 47.6% in ORR) in the published articles. The inconsistency between the protocol/registry and the published article was 31.0% for PFS and 33.5% for ORR. The prespecified outcomes were not reported in 5.2% of the studies evaluating PFS and 4.5% evaluating ORR.This methodological review found that adjudicators were poorly and inconsistently reported between the protocol/registry and the final publication in open-label trials of anticancer drugs.

Background The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. Methods The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. Results Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). Conclusions This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

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.

Background: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated in the Japanese population. 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 clinical characteristics and outcomes 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] and was longer in the HHS group (19.5 days) compared to the DKA groups (16 days). The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0% to 100%. The median ICU stay was 3 days for all groups. 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. The most common complication was infection (18%), followed by pulmonary edema (2.7%), stroke (2.1%), ventricular arrhythmia (1.6%), and deep vein thrombosis (1%). 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)

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.This review aimed to evaluate the effectiveness and safety of carnitine supplementation for the treatment of dialysis-related complications in CKD patients requiring dialysis.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.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.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.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).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.

Aim To develop and validate a model for the early prediction of long-term neurological outcome in patients with non-traumatic out-of-hospital cardiac arrest (OHCA). Methods We analysed multicentre OHCA registry data of adult patients with non-traumatic OHCA who experienced return of spontaneous circulation (ROSC) and had been admitted to the intensive care unit between 2013 and 2017. We allocated 1329 (2013–2015) and 1025 patients (2016–2017) to the derivation and validation sets, respectively. The primary outcome was the dichotomized cerebral performance category (CPC) at 90 days, defined as good (CPC 1–2) or poor (CPC 3–5). We developed 2 models: model 1 included variables without laboratory data, and model 2 included variables with laboratory data available immediately after ROSC. Logistic regression with least absolute shrinkage and selection operator regularization was employed for model development. Measures of discrimination, accuracy, and calibration (C-statistics, Brier score, calibration plot, and net benefit) were assessed in the validation set. Results The C-statistic (95% confidence intervals) of models 1 and 2 in the validation set was 0.947 (0.930–0.964) and 0.950 (0.934–0.966), respectively. The Brier score of models 1 and 2 in the validation set was 0.0622 and 0.0606, respectively. The calibration plot showed that both models were well-calibrated to the observed outcome. Decision curve analysis indicated that model 2 was similar to model 1. Conclusion The prediction tool containing detailed in-hospital information showed good performance for predicting neurological outcome at 90 days immediately after ROSC in patients with OHCA.

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

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.

We aimed to investigate the association between blood urea nitrogen to creatinine ratio (BCR) and survival with favourable neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA).This prospective, multicentre, observational study conducted in Osaka, Japan enrolled consecutive OHCA patients transported to 16 participating institutions from 2012 through 2019. We included adult patients with non-traumatic OHCA who achieved a return of spontaneous circulation and whose blood urea nitrogen and creatinine levels on hospital arrival were available. Based on BCR values, they were divided into: 'low BCR' (BCR10), 'normal BCR' (10 ≤ BCR 20), 'high BCR' (20 ≤ BCR 30), and 'very high BCR' (BCR ≥ 30). We evaluated the association between BCR values and neurologically favourable outcomes, defined as cerebral performance category score of 1 or 2 at one month after OHCA.Among 4415 eligible patients, the 'normal BCR' group had the highest favourable neurological outcome [19.4 % (461/2372)], followed by 'high BCR' [12.5 % (141/1127)], 'low BCR' [11.2 % (50/445)], and 'very high BCR' groups [6.6 % (31/471)]. In the multivariable analysis, adjusted odds ratios for 'low BCR', 'high BCR', and 'very high BCR' compared with 'normal BCR' for favourable neurological outcomes were 0.58 [95 % confidence interval (CI 0.37-0.91)], 0.70 (95 % CI 0.49-0.99), and 0.40 (95 % CI 0.21-0.76), respectively. Cubic spline analysis indicated that the association between BCR and favourable neurological outcomes was non-linear (p for non-linearity = 0.003). In subgroup analysis, there was an interaction between the aetiology of arrest and BCR in neurological outcome (p for interaction0.001); favourable neurological outcome of cardiogenic OHCA patients was lower when the BCR was higher or lower, but not in non-cardiogenic OHCA patients.Both higher and lower BCR were associated with poor neurological outcomes compared to normal BCR, especially in cardiogenic OHCA patients.

Extracorporeal cardiopulmonary resuscitation (ECPR) is performed in refractory out-of-hospital cardiac arrest (OHCA) patients, and the eligibility has been conventionally determined based on three criteria (initial cardiac rhythm, time to hospital arrival within 45 minutes, and age75 years) in Japan. Owing to limited information, this study descriptively determined neurological outcomes after applying the three criteria among OHCA patients who underwent ECPR.This study conducted a post-hoc analysis of data from the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study. This was a multi-institutional prospective observational study of OHCA patients in Osaka Prefecture, Japan. All adult (aged ≥18 years) OHCA patients with internal medical causes treated with ECPR between 1 July 2012 and 31 December 2019 were evaluated. We described one-month neurological favourable outcomes based on the three criteria (initial shockable, time to hospital arrival within 45 minutes, and age75 years), and we compared them using the chi-square test.Among 18,379 patients screened from the CRITICAL study database, we included 517 OHCA patients treated by ECPR; 311 (60.2%) patients met all three criteria. Favourable neurological outcomes were as follows: patients meeting no or one criterion: 2.3% (1/43), those meeting two criteria: 8% (13/163), and those meeting all criteria: 16.1% (50/311) (P-value = 0.004).In this study, approximately 60% of patients treated by ECPR met the three criteria (initial shockable, time to hospital arrival within 45 minutes, and age75 years), and the greater the number of criteria met, the better were the neurological outcomes achieved.

Background: Tranexamic acid is frequently reported to reduce bleeding-related complications in major surgery and trauma. We aimed to investigate whether tranexamic acid reduced hematoma size after percutaneous kidney biopsy. Methods: We conducted a double-blind, parallel three-group, randomized placebo-controlled trial at a teaching hospital in Japan between January 2016 and July 2018. Adult patients with clinical indication for ultrasound-guided percutaneous biopsy of a native kidney were included. Participants were randomly assigned into three groups: high-dose tranexamic acid (1,000 mg in total), low-dose tranexamic acid (500 mg in total), or placebo (counterpart saline). Intervention drugs were intravenously administered twice, as a bolus just before the biopsy and as a continuous infusion initiated just after the biopsy. Primary outcome was post-biopsy perirenal hematoma size as measured by ultrasound on the morning after the biopsy. Results: We assessed 90 adult patients for study eligibility, of whom 56 were randomly allocated into the three groups: 20 for high-dose tranexamic acid, 19 for low-dose tranexamic acid, and 17 for placebo. The median size of perirenal hematoma was 200 mm2 (interquartile range, 21–650) in the high-dose tranexamic acid group, 52 mm2 (0–139) in the low-dose tranexamic acid group, and 0 mm2 (0–339) in the placebo group (p = 0.048 for high-dose tranexamic acid vs. placebo). Conclusion: In this trial, the median size of post-kidney biopsy hematoma was unexpectedly larger in the high-dose tranexamic acid group than in the placebo group. Although our results do not support the routine use of tranexamic acid in percutaneous kidney biopsy at present, further studies are needed to confirm the results.

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 (CRITI-CAL) 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

Estimating prognosis of patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) is essential for selecting candidates. The TiPS65 score can predict neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) treated with ECPR. We aimed to perform an external validation of this score.Data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a multicentred, nationwide, prospectively registered database, were analysed. All adult patients with OHCA and shockable rhythm and treated with ECPR between January 2018 to December 2019 were included. In the TiPS65 score, age, call-to-hospital arrival time, initial cardiac rhythm at hospital arrival, and initial pH value were used as predictors. The primary outcome was 30-day survival with favourable neurological outcomes (Cerebral Performance Category 1 or 2). Discrimination, using the C-statistic, and predictive performances of each score, such as sensitivity and specificity, were investigated.Of 590 included patients (517 [81.6%] men; median [interquartile range] age, 60 [50-69] years), 64 (10.8%) reported favourable neurological outcomes. The C-statistic of the TiPS65 score was 0.729 (95% confidence interval (CI): 0.672-0.786). When the cut-off of TiPS65 score was set to1, the sensitivity and specificity were 0.906 (95%CI: 0.807-0.965) and 0.430 (95%CI: 0.387-0.473), respectively; conversely, when the cut-off was set to3, they were 0.172 (95%CI: 0.089-0.287) and 0.971 (95%CI: 0.953-0.984), respectively.The TiPS65 score shows reasonable discrimination and predictive performances. This score can be supportive in the decision-making process for the selection of eligible patients for ECPR in clinical settings.

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.

Background Pelvic fractures are common among blunt trauma patients, and timely and accurate diagnosis can improve patient outcomes. However, it remains unclear whether physical examinations are sufficient in this context. This study aims to perform a systematic review and meta-analysis of studies on the diagnostic accuracy and clinical utility of physical examination for pelvic fracture among blunt trauma patients. Methods Studies were identified using the MEDLINE, EMBASE, and CENTRAL databases starting from the creation of the database to January 2020. A total of 20 studies (49,043 patients with 8300 cases [16.9%] of pelvic fracture) were included in the quality assessment and meta-analysis. Two investigators extracted the data and evaluated the risk of bias in each study. The meta-analysis involved a hierarchical summary receiver operating curve (ROC) model to calculate the diagnostic accuracy of the physical exam. Subgroup analysis assessed the extent of between-study heterogeneity. Clinical utility was assessed using decision curve analysis. Results The median prevalence of pelvic fracture was 10.5% (interquartile range, 5.1–16.5). The pooled sensitivity (and corresponding 95% confidence interval) of the hierarchical summary ROC parameters was 0.859 (0.761–0.952) at a given specificity of 0.920, which was the median value among the included studies. Subgroup analysis revealed that the pooled sensitivity among patients with a Glasgow Coma Scale score ≥ 13 was 0.933 (0.847–0.998) at a given specificity of 0.920. The corresponding value for patients with scores ≤ 13 was 0.761 (0.560–0.932). For threshold probability Conclusion Imaging tests should be performed in all trauma patients regardless of findings from physical examination or patients’ levels of consciousness. However, the clinical role of physical examination should be considered given the prevalence and threshold probability in each setting.

Background: Serum lactate reflects hypoxic insult in many conditions, but its role as prognostic markers after cardiac arrest is still controversial. This study aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA).Methods:We analyzed the data of the Osaka Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study, a prospective multicenter observational study of 14 participating institutions in Osaka Prefecture, Japan that enrolled consecutive OHCA patients. We included adult nontraumatic OHCA patients transported to the hospital with ongoing CPR from 2013 to 2017. Based on the serum lactate levels during CPR, the patients were divided into four quartiles: Q1 (lactate ≤ 10.6 mEq/L), Q2 (10.6 < lactate ≤ 14.1 mEq/L), Q3 (14.1 < lactate ≤ 18.0 mEq/L), and Q4 (lactate > 18.0 mEq/L). The primary outcome of this study was 1-month survival. Results:A total of 11,960 patients were registered and 4,978 of them were eligible for our analyses. The Q1 group had the highest 1-month survival (4.3% [53/1,245]), followed by Q2 (2.5% [31/1,245]), Q3 (1.1% [14/1,328]), and Q4 (0.5% [6/1,160]) groups. In the multivariable logistic regression analysis, the proportion of 1-month survival in the Q4 group was significantly lower than that in the Q1 group (adjusted odds ratio 0.21; 95% confidence interval 0.086 to 0.50). One-month survival decreased in a stepwise manner as the quartiles increased (p for trend CONCLUSION:High serum lactate level during CPR was associated with poor 1-month survival in OHCA patients. Serum lactate may be one of the effective prognostic indications for OHCA during CPR, especially in patients with non-shockable rhythm.

IntroductionThe aim of this trial was to investigate whether a digital device that provides real-time visualized brushing instructions would contribute to the removal of dental plaque over usual brushing instructions.MethodsWe conducted a single-center, parallel-group, stratified permuted block randomized control trial with 1:1 allocation ratio. Eligibility criteria included people aged ≥ 18 years, and exclude people who met the following criteria: severely crowded teeth; using interdental cleaning implement; having external injury in the oral cavity, or stomatitis; having less than 20 teeth; using orthodontic apparatus; visited to a dental clinic; having the possibility of consulting a dental clinic; having a dental license; not owning a smartphone or tablet device; smoker; taken antibiotics; pregnant; an allergy to the staining fluid; and employee of Sunstar Inc. All participants received tooth brushing instructions using video materials and were randomly assigned to one of two groups for four weeks: (1) an intervention group who used the digital device, providing real-time visualized instructions by connection with a mobile application; and (2) a control group that used a digital device which only collected their brushing logs. The primary outcome was the change in 6-point method plaque control record (PCR) score of all teeth between baseline and week 4. The t-test was used to compare the two groups in accordance with intention-to-treat principles.ResultsAmong 118 enrolled individuals, 112 participants were eligible for our analyses. The mean of PCR score at week 4 was 45.05% in the intervention group and 49.65% in the control group, and the change of PCR score from baseline was -20.46% in the intervention group and -15.77% in the control group (p = 0.088, 95% confidence interval -0.70-10.07).ConclusionsA digital device providing real-time visualized brushing instructions may be effective for the removal of dental plaque.

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 aged18 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 aged1 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.

Background We aimed to identify the association of pH value in blood gas assessment with neurological outcome among out-of-hospital cardiac arrest (OHCA) patients treated by extracorporeal cardiopulmonary resuscitation (ECPR). Methods We retrospectively analysed the database of a multicentre prospective observational study to collect pre-hospital and in-hospital data among OHCA patients in Osaka prefecture, Japan (CRITICAL study), from 1 July 2012 to 31 December 2016. We included the adult OHCA patients treated by ECPR with blood gas assessment before starting ECPR. Patients with OHCA of external causes, such as trauma, were excluded. The patients were divided into three approximately equal groups based on the pH values. We conducted logistic regression analysis to identify the odds ratio (OR) and 95% confidence interval (CI) of the groups for the 1-month neurological favourable outcome adjusted by the potential confounders of sex, age, witnessed by bystander, CPR by bystander, pre-hospital initial cardiac rhythm, and cardiac rhythm on hospital arrival. Results Among the 9,822 patients in the database, 260 patients were finally included in the analysis. The three groups were Tertile 1: pH ≥7.030, Tertile 2: pH 6.875-7.029, and Tertile 3: pH

BackgroundThe study aims to perform systematic review and meta-analysis to identify the diagnostic accuracy of physical examination for pelvic fracture among the blunt trauma patients.MethodWe will perform a systematic review and meta-analysis for diagnostic test accuracy (DTA). We will include all reports on the diagnostic accuracy of physical examinations for detecting pelvic fractures. We will include the studies designed as prospective or retrospective observational (cohort or cross-sectional) studies or secondary analysis of randomized controlled trials. The target participants are blunt trauma patients with potential pelvic injury. The target condition is pelvic fracture. The index test being investigated is physical examination for pelvic fracture. The reference standard is X-ray or computed tomography to confirm the target condition. We will search MEDLINE, EMBASE and The Cochrane Library inclusive of Cochrane Controlled Trials Register. Two authors will independently screen the study eligibility and extract data. Screening will be a two-step process with initial title/abstract screening followed by full-text screening. We will evaluate the risk of bias independently by two investigators and reported according to the QUADAS-2 tool. In the meta-analysis, we will use a bivariate random-effects model to report the summary receiver operating characteristic (SROC) point (summary values for sensitivity and specificity) and the 95% confidence region around the summary ROC point.Trial registrationThis review is submitted with University hospital medical information network clinical trial registry (UMIN-CTR) [UMIN000038785].

Background: Serum lactate reflects hypoxic insult in many conditions, but its role as prognostic markers after cardiac arrest is still controversial. This study aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA). Methods: This study analyzed the data of the Osaka Comprehensive Registry of Intensive Care for OHCA Survival, a prospective multicenter observational study of 14 participating institutions in Osaka Prefecture, Japan. We enrolled consecutive patients aged ≥18 years who were transported to the hospital with ongoing CPR from 2013 to 2016. Based on the serum lactate levels, OHCA patients were divided into 4 quartiles: Q1 (lactate ≤10.6 mEq/L), Q2 (10.6< lactate ≤14.1 mEq/L), Q3 (14.1< lactate ≤18.0 mEq/L) and Q4 (lactate >18.0 mEq/L). The relationships between serum lactate level before return of spontaneous circulation (ROSC) and 1-month survival were assessed. Results: A total of 3,674 OHCA patients were included in the analysis. Overall 1-month survival was 2.3% (88/3,674). The Q1 group had the highest 1-month survival (4.6% [42/921]), followed by Q2 (2.7% [25/920]), Q3 (1.1% [11/966]) and Q4 (0.6% [5/867]), respectively (p for trend < 0.001). In the multivariable logistic regression analysis, the proportion of 1-month survival in the Q4 group was significantly lower, compared with that in the Q1 group (adjusted odds ratio 0.23; 95% confidence interval 0.09 to 0.60). The adjusted proportion of 1-month survival decreased in a stepwise manner across increasing quartiles (p for trend Conclusions: The high serum lactate level before ROSC significantly associated with the worse 1-month survival after OHCA. Serum lactate may be one of the effective prognostic indications for OHCA during CPR, especially with non-shockable initial rhythm.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines., other authors: Satoru Hashimoto,Daisuke Hasegawa,Junji Hatakeyama,Naoki Hara,Naoki Higashibeppu,Nana Furushima,Hirotaka Furusono,Yujiro Matsuishi,Tasuku Matsuyama,Yusuke Minematsu,Ryoichi Miyashita,Yuji Miyatake,Megumi Moriyasu,Toru Yamada,Hiroyuki Yamada,Ryo Yamamoto,Takeshi Yoshida,Yuhei Yoshida,Jumpei Yoshimura,Ryuichi Yotsumoto,Hiroshi Yonekura,Takeshi Wada,Eizo Watanabe,Makoto Aoki,Hideki Asai,Takakuni Abe,Yutaka Igarashi,Naoya Iguchi,Masami Ishikawa,Go Ishimaru,Shutaro Isokawa,Ryuta Itakura,Hisashi Imahase,Haruki Imura,Takashi Irinoda,Kenji Uehara,Noritaka Ushio,Takeshi Umegaki,Yuko Egawa,Yuki Enomoto,Kohei Ota,Yoshifumi Ohchi,Takanori Ohno,Hiroyuki Ohbe,Kazuyuki Oka,Nobunaga Okada,Yohei Okada,Hiromu Okano,Jun Okamoto,Hiroshi Okuda,Takayuki Ogura,Yu Onodera,Yuhta Oyama,Motoshi Kainuma,Eisuke Kako,Masahiro Kashiura,Hiromi Kato,Akihiro Kanaya,Tadashi Kaneko,Keita Kanehata,Ken-ichi Kano,Hiroyuki Kawano,Kazuya Kikutani,Hitoshi Kikuchi,Takahiro Kido,Sho Kimura,Hiroyuki Koami,Daisuke Kobashi,Iwao Saiki,Masahito Sakai,Ayaka Sakamoto,Tetsuya Sato,Yasuhiro Shiga,Manabu Shimoto,Shinya Shimoyama,Tomohisa Shoko,Yoh Sugawara,Atsunori Sugita,Satoshi Suzuki,Yuji Suzuki,Tomohiro Suhara,Kenji Sonota,Shuhei Takauji,Kohei Takashima,Sho Takahashi,Yoko Takahashi,Jun Takeshita,Yuuki Tanaka,Akihito Tampo,Taichiro Tsunoyama,Kenichi Tetsuhara,Kentaro Tokunaga,Yoshihiro Tomioka,Kentaro Tomita,Naoki Tominaga,Mitsunobu Toyosaki,Yukitoshi Toyoda,Hiromichi Naito,Isao Nagata,Tadashi Nagato,Yoshimi Nakamura,Yuki Nakamori,Isao Nahara,Hiromu Naraba,Chihiro Narita,Norihiro Nishioka,Tomoya Nishimura,Kei Nishiyama,Tomohisa Nomura,Taiki Haga,Yoshihiro Hagiwara,Katsuhiko Hashimoto,Takeshi Hatachi,Toshiaki Hamasaki,Takuya Hayashi,Minoru Hayashi,Atsuki Hayamizu,Go Haraguchi,Yohei Hirano,Ryo Fujii,Motoki Fujita,Naoyuki Fujimura,Hiraku Funakoshi,Masahito Horiguchi,Jun Maki,Naohisa Masunaga,Yosuke Matsumura,Takuya Mayumi,Keisuke Minami,Yuya Miyazaki,Kazuyuki Miyamoto,Teppei Murata,Machi Yanai,Takao Yano,Kohei Yamada,Naoki Yamada,Tomonori Yamamoto,Shodai Yoshihiro,Hiroshi Tanaka,Osamu Nishida, Guidelines

Key Points Question Can the neurological outcome of patients with out-of-hospital cardiac arrest and shockable rhythm who are treated with extracorporeal cardiopulmonary resuscitation (ECPR) be predicted using accessible information? Findings In this prognostic study of 916 patients, a model using time to hospital arrival, pH in initial blood gas assessment, shockable rhythm on hospital arrival, and being younger than 65 years was developed to predict survival with good neurological outcome. The model had good performance and was well calibrated. Meaning These findings suggest that this model may be useful for predicting the neurological outcomes of patients with out-of-hospital cardiac arrest and shockable rhythm treated with ECPR., This prognostic study develops and validates a prediction model for neurological outcomes of patients with out-of-hospital cardiac arrest with shockable rhythm treated with extracorporeal cardiopulmonary resuscitation., Importance Extracorporeal cardiopulmonary resuscitation (ECPR) is expected to improve the neurological outcomes of patients with refractory cardiac arrest; however, it is invasive, expensive, and requires substantial human resources. The ability to predict neurological outcomes would assist in patient selection for ECPR. Objective To develop and validate a prediction model for neurological outcomes of patients with out-of-hospital cardiac arrest with shockable rhythm treated with ECPR. Design, Setting, and Participants This prognostic study analyzed data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a multi-institutional nationwide cohort study that included 87 emergency departments in Japan. All adult patients with out-of-hospital cardiac arrest and shockable rhythm who were treated with ECPR between June 2014 and December 2017 were included. Patients were randomly assigned to the development and validation cohorts based on the institutions. The analysis was conducted between November 2019 and August 2020. Exposures Age (

A 64-year-old man presented to our hospital because of dyspnoea. Twenty years ago, he had started peritoneal dialysis (PD) for chronic kidney disease. He had been diagnosed with secondary hyperparathyroidism 7 years before his presentation to our hospital, with an intact parathyroid hormone (PTH) 1227 pg/mL (normal range 10–60 pg/mL), calcium level of 10.1 mg/dL (normal range 8.8–10.5 mg/dL), phosphorus level of 5.5 mg/dL (normal range 2.4–4.1 mg/dL) and alkaline phosphatase level of 377 IU/L (normal range 140–338 IU/L). His medications included cinacalcet. Ultrasonography showed a 5-milimetre nodule at the lower pole of the parathyroid, but 99mTc-hexakis2- methoxyisobutylisonitrile (MIBI)scintigraphy revealed no abnormal accumulation. The patient’s intact PTH increased to 2606 pg/mL 6 years prior to presentation. At that time, the patient deferred parathyroidectomy. A year later, he switched from PD to haemodialysis. Intact PTH remained elevated …

The ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type I domain 13) related markers were measured in the plasma of healthy volunteers and thrombotic microangiopathy (TMA) patients including thrombotic thrombocytopenic purpura (TTP) to examine their efficacy in the diagnosis of TTP. The plasma levels of the ADAMTS13 antigen and ADAMTS13-factor XI complex were significantly lower in TMA patients with a significant decreased ADAMTS13 activity (and these patients were considered to have TTP) than in the healthy volunteers. The plasma levels of ADAMTS13 antigens closely correlated with those of ADAMTS13-factor XI complex. Autoantibody for ADAMTS 13 was also positive in almost all TTP patients. In addition, the ratio of von Willebrand factor (VWF)/ADAMTS13 activity was significantly high in TTP suggesting that this ratio might be more useful for the differential diagnosis of TTP than the ADAMTS13 assay alone. These findings suggest that ADAMTS13 related markers are useful for the diagnosis and analysis of TTP.