Akira Kawauchi

Objectives: To investigate the prevalence of long-term mental disorders in caregivers of ICU sepsis survivors and examine associations with post-intensive care syndrome (PICS) in patients. Design: Prospective observational study. Setting: Twenty-one mixed ICUs. Patients: Caregivers (the next of kin) of the patients diagnosed with sepsis between November 2020 and April 2022. Interventions: None. Measurements and Main Results: Caregivers and patients were assessed at 3, 6, and 12 months after hospital discharge by telephone and mail. The primary outcome was caregiver mental disorders (mental post-intensive care syndrome-family [PICS-F]). Mixed-effects logistic regression analyses were performed to evaluate the association between caregiver PICS-F and patient PICS. Ninety-four caregiver-patient dyads were analyzed. Caregivers were a median of 67 years old (55–79 yr old), 31 (33.0%) were male, and 41 (43.6%) were spouses. Patients were a median of 74 years old (69–82 yr old), and 54 (57.4%) were male. The prevalence of mental PICS-F did not decrease from 3 to 12 months (43% vs. 42%, respectively), whereas the presence of PICS symptoms in patients decreased from 82% to 62%. In mixed-effects logistic regression, the presence of PICS symptoms in patients was significantly associated with PICS-F (adjusted odds ratio, 3.00; 95% CI, 1.54–5.88; p < 0.01). Among the individual patient PICS domains, only mental PICS was significantly associated with PICS-F (3.71; 2.03–6.77; p < 0.01), whereas physical and cognitive impairments in patients were not. Conclusions: The prevalence of mental PICS-F in caregivers of ICU sepsis survivors was frequent and long-lasting over the first year after hospital discharge. Since it was most strongly associated with patients’ mental disorders rather than physical or cognitive impairments, the mental PICS domain in patients may be an important indicator of PICS-F and should be considered in future studies.

OBJECTIVE: Return-to-work varies among previously employed patients after critical illness. Social determinants of health (SDH) may play a role in this variation. We compared patient characteristics and explored the association between SDH and long-term joblessness among patients who experienced severe COVID-19. DESIGN: A secondary analysis of a prospective nationwide database. SETTINGS: The COVID-19 Recovery Study II (CORES II) study, a nationwide prospective observational study in Japan that examined long-term symptoms and social status over two years following hospitalization. PATIENTS: We included adults hospitalized with severe COVID-19 between April 1 and September 30, 2021, who were employed before hospitalization. SDH included education history and pre-hospitalization employment status. MEASUREMENTS AND MAIN RESULTS: The primary outcome was joblessness at the first- and second-year follow-ups. We used generalized estimating equations for the main analysis to examine longitudinal associations between SDH and joblessness, with the SDH variables entered into the model as separate categorical variables. Of 3297 hospitalized patients, 337 met inclusion criteria. At the first-year follow-up, 275 had returned to work, whereas 62 (18.4%) remained jobless. At the second-year follow-up, 242 (82.3 %) had returned to work, and 52 (17.7%) remained jobless. Patients who were jobless at the first-year follow-up showed more persistent symptoms and greater physical and mental impairment compared with those who returned to work. Among SDH factors, non-permanent employment was associated with joblessness over the 2-year follow-up period (odds ratio 2.35; 95% CI [1.26–4.40]) compared with permanent employment. Education history was not associated with joblessness at the first- or second-year follow-ups. CONCLUSIONS: Non-permanent employment was associated with joblessness during the pandemic after hospitalization for severe COVID-19. Pre-hospitalization employment status may be relevant to long-term social recovery after critical illness.

OBJECTIVES: Establishing an effective “chain of survival” for out-of-hospital cardiac arrest (OHCA) requires addressing gender disparities, which have been reported in both prehospital and in-hospital treatments. However, evidence of gender disparity in extracorporeal cardiopulmonary resuscitation (ECPR), which might contribute to differences in outcomes between sexes, remains limited. We aimed to investigate gender disparities in the administration of ECPR for OHCA. DESIGN: A secondary analysis of a prospective nationwide database. SETTING: The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest (JAAM-OHCA) Registry, a multicenter database from 164 hospitals with emergency departments in Japan, collected data between June 2014 and December 2022. PATIENTS: Adult patients (≥ 18 yr) with OHCA from nonexternal causes who did not achieve return of spontaneous circulation before or upon hospital arrival and were transported to facilities with 24-hour ECPR availability within 60 minutes of emergency call. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was receiving ECPR, defined as emergent venoarterial extracorporeal membrane oxygenation implementation before return of spontaneous circulation within 60 minutes after hospital arrival. Multilevel logistic regression analysis was used to estimate the probability of receiving ECPR, adjusting for center-level and patient-level variables. Among 47,965 eligible patients, 28,754 (60.0%) were male and 19,211 (40.0%) were female. The median age was 78.0 years. ECPR was performed in 1713 male patients (6.0%) compared with 344 female patients (1.8%). After adjusting for potential confounders, male sex was associated with significantly higher odds of receiving ECPR (odds ratio, 1.68; 95% CI, 1.46–1.93). This male predominance was consistent across most subgroups but was not observed in patients with unequivocally eligible or ineligible for ECPR. CONCLUSIONS: ECPR was significantly more frequently performed in male patients with OHCA. Subgroup analyses suggest that gender disparity is particularly evident in cases where indications for ECPR are not clearly defined. Further research is needed to explore the underlying causes of this disparity.

Background: Selecting appropriate patients for extracorporeal cardiopulmonary resuscitation (ECPR) in cases of out‐of‐hospital cardiac arrest remains challenging, particularly for those with initial nonshockable rhythms. Our aim is to develop a prediction score to identify suitable ECPR candidates in patients with initial nonshockable rhythm. Methods: The data were sourced from the SAVE‐J II (Study of Advanced Life Support for Ventricular Fibrillation With Extracorporeal Circulation in Japan II) study, a retrospective multicenter observational study in Japan. Included were adult patients with out‐of‐hospital cardiac arrest who underwent ECPR with initial pulseless electrical activity or asystole. The primary outcome was survival to hospital discharge. We developed a prediction score, employing logistic regression analysis and internally validating it with 1000 bootstrap samples. The performance of the score in predicting a favorable neurological outcome at discharge was also evaluated. Results: Among 648 eligible patients, 86 (13.3%) survived to hospital discharge. The median age was 60.5 years, 75.9% (492) were male, and 74.4% (482) had pulseless electrical activity as the initial rhythm. Three clinical predictors for the START‐ECPR Score (Signs of Life, Transient ROSC, Not Asystole Rhythm to ECPR Score) were identified: shockable rhythm or pulseless electrical activity at hospital arrival, transient return of spontaneous circulation before hospital arrival, and signs of life at hospital arrival. Survival rates were 4.4% (7/159) for a score of 0, 10.7% (38/356) for a score of 1, and 30.8% (39/130) for scores of 2 to –3. The bias‐corrected C‐index for the score was 0.696. For predicting favorable neurologic outcomes at discharge, the C‐index was 0.761. Conclusions: We developed a straightforward 3‐factor prediction score for predicting survival to hospital discharge and favorable neurologic outcomes in patients with out‐of‐hospital cardiac arrest with initial nonshockable rhythms receiving ECPR.

Objective: To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment.Methods: An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors.Results: The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006).Conclusion: Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS.

Background/Objectives: This study investigated the prevalence of functional impairments and the effects of long COVID on long-term functional impairments in patients with severe COVID-19. Methods: We conducted a nationwide multicenter cohort study in collaboration with nine hospitals, collecting data using self-administered questionnaires from participants aged 20 years or older who were diagnosed with COVID-19, admitted to the intensive care unit (ICU) between April 2021 and September 2021, and discharged alive. Questionnaires regarding daily life, sequela, and functional impairments were mailed to patients in August 2022. The effects of long COVID on functional impairments were examined using a multivariate logistic regression analysis. Results: The survey was completed by 220 patients, with a mean of 416 days after discharge. Among respondents, 20.5% had physical impairments (n = 45), 35.0% had mental disorders (n = 77), and 42.7% had either (n = 94). Furthermore, 77.7% had long COVID (171/220), and the most common symptom was dyspnea (40.0%). The multivariate analysis showed that fatigue/malaise, upper respiratory tract symptoms, myalgia, muscle weakness, decreased concentration, sleep disorder, brain fog, and dizziness were risk factors for functional impairments at one year. Conclusions: Many patients with severe COVID-19 admitted to the ICU still suffered from post-intensive care syndrome even after one year, which manifested in combination with direct symptoms of the original disease, such as long COVID.

Background: Post-intensive care syndrome (PICS) affects the quality of life (QOL) of survivors of critical illness. Although PICS persists for a long time, the longitudinal changes in each component and their interrelationships over time both remain unclear. This multicenter prospective study investigated the 2-year trajectory of PICS and its components as well as factors contributing to deterioration or recovery in mechanically ventilated patients with coronavirus disease 2019 (COVID-19), and also attempted to identify possible countermeasures. Methods: Patients who survived COVID-19 requiring mechanical ventilation completed questionnaires on the Barthel index, Short-Memory Questionnaire, Hospital Anxiety and Depression Scale, and EuroQol 5 dimensions 5-level every six months over a two-year period. Scores were weighted to account for dropouts, and the trajectory of each functional impairment was evaluated with alluvial diagrams. The prevalence of PICS and factors impairing or restoring function were examined using generalized estimating equations considering trajectories. Results: Among 334 patients, PICS prevalence rates in the four completed questionnaires were 72.1, 78.5, 77.6, and 82.0%, with cognitive impairment being the most common and lower QOL being noted when multiple impairments coexisted. Physical function and QOL indicated that many patients exhibited consistent trends of either recovery or deterioration. In contrast, cognitive function and mental health revealed considerable variability, with many patients showing fluctuating ratings in the later surveys. Delirium was associated with worse physical and mental health and poor QOL, while prolonged ventilation was associated with poor QOL. Living with family was associated with the recovery of all functions and QOL, while extracorporeal membrane oxygenation (ECMO) was associated with the recovery of cognitive function and mental health. Conclusions: Critically ill patients had PICS for a long period and followed different trajectories for each impairment component. Based on trajectories, known PICS risk factors such as prolonged ventilation and delirium were associated with impaired recovery, while ECMO and the presence of family were associated with recovery from PICS. In critically ill COVID-19 patients, delirium management and family interventions may play an important role in promoting recovery from PICS. Trial registration number: UMIN000041276, August 01, 2020.

Background: Previous studies examining sex differences in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) have indicated that women have favorable outcomes; however, detailed evidence remains lacking. We aimed to investigate sex differences in the backgrounds and outcomes of patients undergoing ECPR for OHCA. Methods: This study was a secondary analysis of the registry from the SAVE-J II study, a retrospective multicenter study conducted in Japan from 2013 to 2018. Adult patients without external causes who underwent ECPR for OHCA were included. The primary outcome was a favorable neurological outcome (Cerebral Performance Status 1 or 2) at hospital discharge. We used multilevel logistic regression to evaluate the association of sex differences, adjusting for center-level (hospital) and individual-level variables (patient background, cardiac arrest situation, and in-hospital intervention factors). For sensitivity analyses, we performed three models of multilevel logistic regression when selecting confounders. Results: Among the 1819 patients, 1523 (83.7%) were men, and 296 (16.3%) were women. The median age (61.0 vs. 58.0 years), presence of a witness (78.8% vs. 79.2%), and occurrence of bystander CPR (57.5% vs. 61.6%) were similar between groups. Women were more likely to present with an initial non-shockable rhythm (31.7% vs. 49.7%), as well as a non-shockable rhythm at hospital arrival (52.1% vs. 61.5%) and at ECMO initiation (48.1% vs. 57.1%). The proportion of favorable neurological outcomes was 12.3% in males and 15.9% in females (p = 0.10). Multilevel logistic regression analysis showed that the female sex was significantly associated with a favorable neurologic outcome at discharge (adjusted odds ratio: 1.60 [95% confidence interval: 1.05–2.43]; p = 0.03). This advantage in women was consistently observed in the sensitivity analyses. Conclusions: The female sex is significantly associated with favorable neurological outcomes at hospital discharge in patients who received ECPR for OHCA.