EMpowerment of PArents in THe Intensive Care: A multicentre validation study in Japan.

BACKGROUND: The importance of assessing family satisfaction in paediatric intensive care units (PICUs) is becoming increasingly recognised. The survey, EMpowerment of Parents in THe Intensive Care "EMPATHIC-30", was designed to assess family satisfaction and has been translated and implemented in several countries but not yet in Japan. OBJECTIVES: The objective of this study was to translate, culturally adapt, and validate the EMPATHIC-30 questionnaire in Japanese and to identify potential factors for family-centred care satisfaction. METHODS: We translated and adapted for patient-reported outcome measures via a 10-step process outlined by the Principles of Good Practice. Four paediatric PICUs in Japan participated in the validation study, and the parental enrolment criterion was a child with a PICU stay of >24 h. Reliability was measured by Cronbach's α, and congruent validity was tested with overall satisfaction-with-care scales by correlation analysis. Multivariate linear regression modelling was conducted to identify factors related to each domain of the Japanese EMPATHIC-30. RESULTS: A total of 163 parents (mean age: 31.9 ± 5.4 years; 81% were mothers) participated. The five domains of the Japanese EMPATHIC-30 showed high reliability (α = 0.87 to 0.97) and congruent validity, demonstrating high correlations with overall satisfaction in nurses (r = 0.75) and doctors (r = 0.76). Multivariate modelling found that elective admission, mechanical ventilation, and parents who had experience of a family member in an adult intensive care unit had higher satisfaction scores in all five domains (p < 0.05). Moreover, Buddhists assigned higher satisfaction scores in the Care and Treatment domain (p = 0.03). CONCLUSIONS: The Japanese EMPATHIC-30 questionnaire has demonstrated adequate reliability and validity measures. We also identified that elective admission, mechanical ventilation, and having previous adult intensive care unit experience of a family member were factors in assigning higher scores for all satisfaction domains. PICU clinicians need to be cognisant of ethical, cultural, and religious factors relating to the critically ill child and their family.

Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial.

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03-1.36), that of a 10 mmHg SBP increase was 1.14 (1.03-1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00-1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.

Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic Therapy 2 Study.

OBJECTIVE: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. METHODS: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. RESULTS: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0. INTERPRETATION: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.

Safety and Effectiveness of Apixaban Versus Warfarin in Japanese Patients with Nonvalvular Atrial Fibrillation Stratified by Renal Function: A Retrospective Cohort Study.

BACKGROUND: We previously conducted a retrospective cohort study using chart review of oral anticoagulant-naïve Japanese patients with nonvalvular atrial fibrillation (NVAF) that assessed the risk of major bleeding and stroke/systemic embolism (SE) events of apixaban versus warfarin. METHODS: In this subgroup analysis, we compared the risk of major bleeding and stroke/SE events by stratifying patients into four subgroups matched 1:1 using propensity score matching (PSM) according to baseline creatinine clearance (CrCl; mL/min): ≥ 15 to < 30, ≥ 30 to < 50, ≥ 50 to < 80, and ≥ 80. RESULTS: Of the 7074 patients in the apixaban group and 4998 in the warfarin group eligible for inclusion in the analysis, 4385 were included in each group after PSM. Incidence rates of major bleeding and stroke/SE events were generally lower with apixaban versus warfarin across the CrCl subgroups. When all patients with a CrCl change of < 0 mL/min per year during the study period (apixaban, n = 3871; warfarin, n = 2635) were stratified into four subgroups based on the magnitude of CrCl decline (median CrCl change [mL/min] per year: - 1.09, - 3.48, - 7.54, and - 36.92 for apixaban, and - 1.10, - 3.65, - 7.85, and - 40.40 for warfarin), the incidence rates of major bleeding and stroke/SE events generally increased with an increasing CrCl decline per year in both groups. CONCLUSIONS: In Japanese patients with NVAF, the safety and effectiveness of apixaban and warfarin were consistent across different renal subgroups, including those with severe renal impairment. Our results highlight the importance of monitoring renal function variations over time in patients with NVAF. GOV IDENTIFIER: NCT03765242.

Soluble C-type lectin-like receptor 2 in stroke (CLECSTRO) study: protocol of a multicentre, prospective cohort of a novel platelet activation marker in acute ischaemic stroke and transient ischaemic attack.

INTRODUCTION: Soluble C-type lectin-like receptor 2 (sCLEC-2) is a new biomarker for platelet activation, which can be easily measured by usual blood collection. We conducted the CLECSTRO, a prospective, observational cohort study, to evaluate the clinical implications of sCLEC-2 in patients with acute ischaemic stroke (AIS) and transient ischaemic attack (TIA). METHODS AND ANALYSIS: The participants are patients with AIS/TIA and control patients required for differentiation from AIS/TIA. The target population is 600, including the patients and controls, who would be recruited from eight stroke centres across Japan. The inclusion criteria are AIS within 24 hours of onset and a modified Rankin Scale (mRS) score of 0-2, TIA within 7 days of onset, and contemporary patients required for differentiation from AIS/TIA. Plasma sCLEC-2 will be measured by high-sensitive chemiluminescent enzyme immunoassay using residual blood samples from routine laboratory examinations at the first visit in all patients and 7 days later or at discharge in patients with AIS/TIA. The outcomes include plasma levels of sCLEC-2 in patients with AIS/TIA and controls, sCLEC-2/D-dimer ratio in non-cardioembolic and cardioembolic AIS/TIA, correlation of sCLEC-2 with recurrence or worsening of stroke, severity of stroke, infarct size, ABCD2 score in TIA and outcome (mRS) at 7 days and 3 months. ETHICS AND DISSEMINATION: This study was approved by the Ethical Committee of the University of Yamanashi as the central ethical committee in agreement with the ethical committees of all collaborative stroke centres. Informed consent will be obtained by an opt-out form from the patients at each stroke centre according to the Ethical Guidelines for Medical and Biological Research Involving Human Subjects by the Japanese Ministry of Health, Labour and Welfare. TRIAL REGISTRATION NUMBERS: NCT05579405, UMIN000048954.

National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study.

OBJECTIVES: To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan. DESIGN: Retrospective study. SETTING: Six hundred and thirty-one primary care institutions in Japan. PARTICIPANTS: Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3-6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1-25 points). RESULTS: In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality. CONCLUSIONS: The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Verifying the Japanese version of the Healthy Aging Brain Care Monitor self-report tool for evaluating post-intensive care syndrome.

BACKGROUND: Post-intensive care syndrome (PICS) requires the use of multiple assessment tools because it affects multiple domains: Cognitive, Functional, and Behavioural/Psychological. Therefore, this study translated the self-report (SR) version of the Healthy Aging Brain Care Monitor (HABC-M), spanning multiple domains, into Japanese and analysed its reliability and validity in a post-intensive care setting. METHODS: Patients aged 20 years or older and admitted to the adult intensive care unit from August 2019 to January 2021 were included and surveyed by questionnaire. The 21-item Dementia Assessment Sheet for the Regional Comprehensive Care System was used to validate cognitive and physical aspects, and the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, and the Post Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders 5th edition were used to validate emotional aspects. Reliability was assessed by Cronbach's alpha, and congruent validity by correlation analysis. Multivariate linear regression models were used to identify potential factors for PICS. RESULTS: A total of 104 patients (mean age: 64 ± 14 years) with 3 median mechanical ventilation days (interquartile range: 2-5) were enrolled. The Cognitive domain of the HABC-M SR was highly correlated with memory and disorientation (r = 0.77 for each), while the Functional domain was highly correlated with Instrumental Activities of Daily Living Scale (r = 0.75-0.79). The Behavioural/Psychological domain highly correlated with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Post Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders 5th edition (r = 0.75-0.76). Multivariate analysis revealed longer ICU stays associated with lower Cognitive and Functional (p = 0.03 for each) domains and longer mechanical ventilation days with a lower Behavioural/Psychological domain (p < 0.01). CONCLUSION: The translated Japanese HABC-M SR showed high validity for assessment of the Cognitive, Functional, and Behavioural/Psychological domains of PICS. Therefore, we recommend that the Japanese version of the HABC-M SR be routinely used in the assessment of PICS.

Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

Dual antiplatelet therapy with cilostazol in stroke patients with extracranial arterial stenosis or without arterial stenosis: A subgroup analysis of the CSPS.com trial.

BACKGROUND: We previously reported that dual antiplatelet therapy (DAPT) with cilostazol was superior to aspirin or clopidogrel for the prevention of recurrent stroke and vascular events in a subgroup analysis of intracranial arterial stenosis in the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com), a randomized controlled trial. AIMS: We conducted another subgroup analysis to investigate the benefit of DAPT with cilostazol in patients with extracranial arterial stenosis (ECAS) and those without arterial stenosis. METHODS: We compared the risk of recurrent ischemic stroke, vascular events, and major bleeding between DAPT with cilostazol plus aspirin or clopidogrel and aspirin or clopidogrel alone in patients with ischemic stroke between 8 and 180 days before starting trial treatment and ECAS or without arterial stenosis. RESULTS: The median follow-up period was 1.4 years. The risk of recurrent ischemic stroke (hazard ratio (HR): 1.04, 95% confidence interval (CI): 0.42-2.57) and vascular events (HR: 0.97, 95% CI: 0.42-2.24) did not differ between the two groups for the 253 patients with ECAS, whereas they were lower (HR: 0.36, 95% CI: 0.18-0.74 and HR: 0.47, 95% CI: 0.26-0.85, respectively) in the DAPT group for the 944 patients without arterial stenosis. The risk of major bleeding did not differ between the groups in patients with ECAS (HR: 0.58, 95% CI: 0.05-6.39) or without arterial stenosis (HR: 0.79, 95% CI: 0.27-2.26). CONCLUSION: DAPT with cilostazol might be beneficial for prevention of recurrent stroke and vascular events in patients without arterial stenosis but not in those with ECAS. DATA ACCESS STATEMENT: We will make the deidentified participant data from this research available to the scientific community with as few restrictions as feasible, while retaining exclusive use until the publication of major output.

Sex Difference in the Impact of Dual Antiplatelet Therapy using Cilostazol for Secondary Stroke Prevention: A Sub-Analysis of CSPS.com.

AIM: Although some sex differences in stroke have been reported, differences in the effects of antiplatelet therapy for secondary stroke prevention have not been clarified. METHODS: In the Cilostazol Stroke Prevention Study combination trial, patients with high-risk, non-cardioembolic ischemic stroke between 8 and 180 days after onset treated with aspirin or clopidogrel alone were recruited and randomly assigned to receive either monotherapy or dual antiplatelet therapy (DAPT) using cilostazol and followed up for 0.5-3.5 years. The primary efficacy outcome was recurrence of ischemic stroke. The safety outcome was severe or life-threatening hemorrhage. Outcomes were analyzed by sex. RESULTS: A total of 1,320 male patients and 558 female patients were included. The male patients had more risk factors than the female patients. In male patients, the primary endpoint occurred at a rate of 2.0 per 100 patient-years in the DAPT group and 5.1 per 100 patient-years in the monotherapy group (hazard ratio (HR), 0.40; 95% confidence interval (CI), 0.23-0.68). In male patients, DAPT prolonged the time to recurrent stroke by 4.02-fold (95% CI, 1.63-9.96) compared with monotherapy. In female patients, the average annual event rates were 2.7 per 100 patient-years in the DAPT group and 3.3 per 100 patient-years in the monotherapy group (HR, 0.82; 95% CI, 0.37-1.84). Safety outcomes did not differ significantly in both male and female patients. CONCLUSIONS: Long-term DAPT using cilostazol reduced the recurrence of ischemic stroke and prolonged the recurrence-free time in male patients, but not in female patients.

Pediatric delirium is associated with increased brain injury marker levels in cardiac surgery patients.

Despite global consensus on the importance of screening pediatric delirium, correlations between pediatric delirium during acute brain injury and adult delirium are unclear. Therefore, we hypothesized that similar pediatric biomarkers reflect acute brain injury as in adult delirium. We observed pediatric cardiac surgery patients from neonatal age to 18 years, who were admitted to our pediatric intensive care unit after cardiovascular operations between October 2019 to June 2020, up to post-operative day 3 (4 days total). We recorded age, sex, risk score (Risk Adjustment in Congenital Heart Surgery [RACHS-1]), midazolam/dexmedetomidine/fentanyl dosage, and pediatric Sequential Organ Failure Assessment (pSOFA). Richmond Agitation-Sedation Scale (RASS), Cornell Assessment of Pediatric Delirium (CAPD), Face, Leg, Activity, Consolability (FLACC) behavioral scale, and Withdrawal Assessment Tool (WAT-1) scales were used and serum sampling for neuron specific enolase (NSE) was conducted. Consciousness status was considered hierarchical (coma > delirium > normal) and associations between conscious status and NSE were conducted by hierarchical Bayesian modeling. We analyzed 134 data points from 40 patients (median age 12 months). In the multi-regression model, NSE was positively associated with coma [posterior odds ratio (OR) = 1.1, 95% credible interval (CrI) 1.01-1.19] while pSOFA [posterior OR = 1.63, 95% CrI 1.17-2.5], midazolam [posterior OR = 1.02, 95% CrI 1.01-1.04], and dexmedetomidine [posterior OR = 9.52, 95% CrI 1.02-108.85] were also associated. We also evaluated consciousness state probability at each NSE concentration and confirmed both that consciousness was hierarchically sorted and CAPD scores were also associated with NSE [posterior OR = 1.32, 95% CrI 1.09-1.58]. "Eye contact" (r = 0.55) was the most correlated component with NSE within the pain, withdrawal syndrome, and PD items. PD within the hierarchy of consciousness (coma, delirium, normal) and CAPD scores are associated with brain injury marker levels. Using pediatric delirium assessment tools for monitoring brain injury, especially eye contact, is a reliable method for observing PD.

Effect of Simultaneous Dual-Task Training on Regional Cerebral Blood Flow in Older Adults with Amnestic Mild Cognitive Impairment.

BACKGROUND: No previous study has examined the effect of dual-task training using changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) as an outcome. OBJECTIVE: This study aimed to examine the effects of simultaneous dual-task training of exercise and cognitive tasks on rCBF using SPECT in older adults with amnestic mild cognitive impairment (aMCI). METHODS: In this non-randomized control trial, 40 older adults with aMCI participated from May 2016 to April 2018. Outpatients in the intervention group (n = 22) underwent 24 sessions (12 months) of dualtask training twice a month for 60 mins per session. Participants in the control group (n = 18) continued to have regular outpatient visits. The primary outcome was rCBF at baseline and after 12 months, which was compared in each group using the two-sample t-test. The secondary outcomes were the rate of reversion and conversion from aMCI after 12 months. RESULTS: Of the 22 participants in the intervention group, six dropped out; therefore, 16 were included in the analysis. The intervention group showed more significant increases in rCBF in multiple regions, including the bilateral frontal lobes, compared with the control group. However, the rates of reversion or conversion from mild cognitive impairment (MCI) were not significantly different. CONCLUSION: Dual-task training for older adults with aMCI increased rCBF in the frontal gyrus but did not promote reversion from MCI to normal cognition. Future intervention studies, such as follow-up examinations after the intervention, are warranted to consider long-term prognosis.

PERSonality, Ehical, and PROfessional quality of life in Pediatric/Adult Intensive Nurses study: PERSEPRO PAIN study.

BACKGROUND: The World Health Organization included burnout syndrome criteria that reduce both professional quality of life and work satisfaction in its 11th Revision of the International Classification of Diseases in 2019 while nursing bodies have issued action calls to prevent burnout syndrome. Despite this, the effect of social factors, personality traits and cross-interaction on professional quality of life is still unclear. AIM: To reveal the association between ethical climate, personal trait and professional quality of life. METHOD: An online survey of registered nurses working in adult, pediatric or both ICUs. We used the ten-item personality measure based on The Big Five theory and Type-D personality Scale-14 then measured the ethical climate with the Hospital Ethical Climate Survey and the professional domains of burnout syndrome, secondary traumatic stress and compassion satisfaction by the Professional Quality of Life Scale Version 5 simultaneously. Multivariate analysis confirmed the triangular association of hospital ethical climate, personality traits and professional quality of life. RESULT: We enrolled 310 participants from September 2019 to February 2020. Mean age was 33.1 years (± 5.9) and about 70% were female. In the multivariate analysis, neuroticism (p = 0.03, p = 0.01) and Type D personality (both of p<0.01) were associated with burnout syndrome and secondary traumatic stress while agreeableness (p<0.01) was associated with secondary traumatic stress. Conversely, extraversion (p = 0.01), agreeableness (p<0.01) and openness (p<0.01) were associated with compassion satisfaction. We also observed interactions between hospital ethical climate and conscientiousness (p = 0.01) for burnout syndrome and secondary traumatic stress. Neuroticism was related to (p<0.01) BOS and compassion satisfaction while Type D personality (p<0.01) correlated with burnout syndrome and secondary traumatic stress. CONCLUSION: Hospital ethical climate strongly affects professional quality of life in nurses with specific personality traits. Therefore, it is important to maintain an ethical hospital climate, considering individual personalities to prevent burnout syndrome.

Association of Timing for Starting Dual Antiplatelet Treatment With Cilostazol and Recurrent Stroke: A CSPS.com Trial Post Hoc Analysis.

BACKGROUND AND OBJECTIVES: Long-term treatment with the combination of cilostazol with aspirin or clopidogrel showed a lower risk of stroke recurrence compared to aspirin or clopidogrel alone after high-risk noncardioembolic ischemic stroke in a randomized trial. We aimed to determine whether the effect of the dual medication compared to monotherapy on risk of recurrent ischemic stroke differs according to timing of starting medication after stroke onset. METHODS: In a subanalysis of the randomized controlled trial, patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone or a combination of cilostazol with aspirin or clopidogrel. They were divided into 3 groups according to the timing of starting trial treatment: between 8 and 14 days after stroke onset (8-14 days group), between 15 and 28 days after stroke onset (15-28 days group), and between 29 and 180 days after stroke onset (29-180 days group). The primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding. RESULTS: Of 1,879 patients, 498 belonged to the 8-14 days group, 467 to the 15-28 days group, and 914 to the 29-180 days group. There was a significant treatment-by-subgroup interaction for the recurrence of ischemic stroke between trial treatment and trichotomized groups. The recurrence of ischemic stroke was less common with dual therapy than with monotherapy in the 15-28 days group (annualized rate 1.5% vs 4.9%, respectively; adjusted hazard ratio 0.34 [95% CI 0.12-0.95]) and the 29-180 days group (1.9% vs 4.4%, respectively; 0.27 [0.12-0.63]) and similarly common in the 8-14 days group (4.5% for both; 1.02 [0.51-2.04]). Severe or life-threatening bleeding occurred similarly between patients on dual therapy and those on monotherapy in any of the trichotomized groups (crude hazard ratio 0.22 [95% CI 0.03-1.88] in the 8-14 days group, 1.07 [0.15-7.60] in the 15-28 days group, and 0.76 [0.24-2.39] in the 29-180 days group). DISCUSSION: Long-term dual antiplatelet therapy using cilostazol starting 15-180 days after stroke onset, compared to therapy started 8-14 days after onset, was more effective for secondary stroke prevention than monotherapy without increasing hemorrhage risk. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT01995370; UMIN Clinical Trials Registry 000012180. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute noncardioembolic stroke taking either aspirin or clopidogrel, the addition of cilostazol 15-180 days after stroke onset decreases the risk of recurrent ischemic stroke.

COVID-19 vaccine induced interstitial lung disease.

A 60-year-old man presented with dyspnea four days after the second dose of the coronavirus disease (COVID-19) vaccine. Imaging revealed extensive ground-glass opacification. Blood tests were notable for elevated KL-6 levels. Bronchoalveolar lavage fluid analysis showed increased lymphocyte-dominant inflammatory cells and decreased CD4/CD8 ratio. These findings were consistent with the diagnosis of drug-induced interstitial lung disease (DIILD). To the best of our knowledge, this has never been reported in previous literature. Treatment with glucocorticoids relieved his symptoms. This paper highlights that although extremely rare, COVID-19 vaccine could cause DIILD, and early diagnosis and treatment are crucial to improve patient outcomes.

Trousseau's Syndrome Presenting as Multiple Cerebral Infarctions Caused by Mucin-producing Bladder Micropapillary Urothelial Cancer.

We herein report a 70-year-old man with recurrent multiple cerebral infarctions under warfarin therapy who was finally diagnosed with Trousseau's syndrome resulting from advanced bladder cancer. A histological examination of the mesenteric lymph nodes revealed metastasis of micropapillary urothelial cancer with positive mucin markers CA125 and MUC1. Blood examinations also indicated elevated tumor markers, such as CA19-9 and CA125. To our knowledge, this is the first report of Trousseau's syndrome in a patient with bladder micropapillary urothelial cancer in which mucin involvement was clearly proven by histological and serological examinations.

Comparative Safety and Effectiveness of Apixaban vs. Warfarin in Oral Anticoagulant-Naïve Japanese Patients With Non-Valvular Atrial Fibrillation　- A Retrospective Chart Review Study.

BACKGROUND: The risk of bleeding and stroke/systemic embolism (SE) events associated with apixaban vs. warfarin among oral anticoagulant-naïve Japanese patients with non-valvular atrial fibrillation (NVAF) has not been well studied in daily clinical practice.Methods and Results:Clinical data for 12,090 patients were retrospectively extracted from the medical records of patients with NVAF (aged ≥20 years, creatinine clearance [CrCl] ≥15 mL/min) newly initiated to apixaban or warfarin treatment between January 1, 2010, and December 31, 2017, at 315 general practitioner clinics and 87 hospitals across Japan. After applying propensity score matching, patient characteristics were well-balanced between the apixaban and warfarin groups (4,523 patients each). The incidence rate (per 100 person-years) of major bleeding was lower in the apixaban vs. warfarin group (1.17 vs. 1.64; hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.54-0.93; P=0.01), as was that of stroke/SE (1.14 vs. 1.73; HR, 0.65; 95% CI, 0.50-0.85; P<0.01). When patients were stratified by CrCl (≥50 mL/min and <50 mL/min), the P value for interaction was not statistically significant between subgroups (P=0.31 for major bleeding and P=0.32 for stroke/SE). CONCLUSIONS: The benefit of apixaban over warfarin for the reduction in risk of major bleeding and stroke/SE could be generalizable to daily clinical practice and to patients with reduced renal function.

Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis.

Background Long-term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high-risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23-0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26-0.91) were lower in DAPT than SAPT, whereas the risk of severe or life-threatening bleeding (HR, 0.72; 95% CI, 0.12-4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370.

Severity and prevalence of burnout syndrome in paediatric intensive care nurses: A systematic review.

OBJECTIVES: The aim of this study is to identify burnout syndrome severity and prevalence in paediatric intensive care unit nurses. DESIGN: Systematic review. SETTING: Paediatric intensive care unit. MAIN OUTCOME MEASURES: A librarian was consulted on methodology before the search process. MEDLINE (via PubMed), EMBASE, the Cochrane Library, CINAHL, and PsycINFO were searched for full-text studies published before September 2019 in any language. Only those observational studies exploring burnout syndrome, including paediatric intensive care unit nurses, were included. Two authors independently screened studies. We assessed the risk of bias within each study based on the Office of Health Assessment and Translation tool. RESULT: After screening 1238 articles, we identified six studies which met the systematic review criteria. All studies included were published after 2012 and participant sample sizes were between 35 and 195 nurses. Three studies were conducted in the United States of America while the others were from the United Kingdom, Turkey and Taiwan. Prevalence of burnout syndrome in pediatric intensive care unit nurses was reported in these studies as between 42% and 77%. The assessment tools used in these studies were the (abbreviated) Maslach Burnout Inventory, Abbreviated Maslach Burnout Inventory, Occupational Burnout Inventory, and Professional Quality of Life Scale Version 5. We could not conduct a meta-analysis due to the lack of studies. CONCLUSION: Our systematic review identifies that a low number (6 total) of relevant studies focused on burnout syndrome for pediatric intensive care unit nurses with a prevalence of burnout syndrome in paediatric intensive care unit nurses of between 42% and 77%.