神田 直樹

OBJECTIVES: To evaluate how heterogeneous diagnostic definitions of persistent inflammation, immunosuppression, and catabolism syndrome (PICS), identified through a systematic review, influence patient identification and associated clinical outcomes when applied to a nationwide Japanese ICU cohort. DESIGN: Systematic review and retrospective cohort study. SETTING: The multicenter inpatient administrative claims database with laboratory test values in Japan. PATIENTS: Critically ill adult patients admitted to ICUs in Japan between March 2010 and September 2021. A total of 215,474 ICU patients were analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A systematic review identified 23 clinical studies using varying diagnostic criteria for PICS. Definitions differed substantially in laboratory thresholds, assessment timing, and inclusion requirements. PICS definitions extracted from the review were applied to the Medical Data Vision cohort, and overlap among definitions was assessed using an UpSet plot. The number of patients meeting each definition varied widely (211-47,888 patients), demonstrating that even small differences in thresholds or timing markedly influence patient identification. The prevalence of PICS varied widely across definitions (range, 0.1-22.2%). In-hospital mortality also showed marked variability (range, 11.4-64.0%). Functional outcomes were consistently poor, with a high proportion of patients discharged with a Barthel Index less than 90 (range, 46.5-78.9%) and a prolonged hospital stay greater than 28 days (range, 54.9-94.7%). CONCLUSIONS: The present study revealed marked heterogeneity among existing PICS definitions, resulting in wide variations in prevalence and outcomes. Despite this variability, PICS consistently identified patients with prolonged hospitalization and physical impairment. These findings highlight the need for standardized diagnostic criteria to improve comparability across studies and support earlier identification and intervention for at-risk ICU survivors.

BackgroundPersistent inflammation, immunosuppression, and catabolism syndrome (PICS) that develops following critical illness is one of the most challenging issues in critical care medicine. While corticosteroids are widely used in septic shock, their impact on PICS remains unclear. While corticosteroids may reduce inflammation, they potentially increase infection risk and affect muscle function.MethodsThis retrospective cohort study analyzed 3186 patients with septic shock from a Japanese administrative claims database, which was supplied by Medical Data Vision Co., Ltd (Tokyo, Japan). Using propensity score matching, we compared outcomes between patients who received corticosteroids within the first two days of admission (steroid group) and those who did not (control group). The primary outcome was the incidence of PICS on day 28, defined as meeting at least two of the following criteria: C-reactive protein >2.0 mg/dL, albumin <3.0 g/dL, and lymphocyte count <800/μL.ResultsA total of 4054 patients were enrolled in this retrospective cohort study. After the exclusion of 868 patients, 3186 eligible patients (906 in the steroid group and 2280 in the control group) were included in the propensity score analysis. After matching, there was no significant difference in the incidence of PICS on day 28 between the steroid and control groups (16.7% vs 13.6%; risk difference, 2.22%; 95% CI, -1.89% to 6.34%; P = 0.095). Additionally, no significant differences were observed in 28-day mortality (15.2% vs 15.2%), in-hospital mortality, PICS on day 14, the Barthel Index at discharge or the percentage of patients meeting PICS criteria for each component on day 14 and day 28.ConclusionsThe administration of corticosteroids in patients with septic shock was not associated with the incidence of PICS.

OBJECTIVES: To describe trends in the incidences of chronic hepatitis C, hepatocellular carcinoma (HCC), and related healthcare burden after the introduction of interferon-free direct-acting antivirals (DAAs). METHODS: This repeated cross-sectional study (time trend analysis) examined chronic hepatitis C and related healthcare, including HCC, using national claims data covering >98% of healthcare services in Japan between fiscal years 2013 and 2022. RESULTS: During the study period, 357,877 patients were treated with DAAs. The prevalence of individuals receiving care for chronic hepatitis C decreased by 40% (95% confidence interval [CI]: 40-40%), from 0.54% in 2013 to 0.33% in 2022. Among individuals with HIV, the reduction was smaller, at 16% (95% CI: 10-20%), with a prevalence of 3.82% in 2022. The annual incidence of newly diagnosed HCC decreased by 69% (95% CI: 68-70%), accompanied by a reduction in HCC treatments. Annual healthcare costs for individuals with chronic hepatitis C peaked in 2015 and decreased to 65% of 2013 levels by 2022. CONCLUSION: During the 10-y DAA era, the healthcare burden of hepatitis C declined substantially in Japan. Enhanced efforts in prevention, screening, and treatment are critical for the eradication of hepatitis C, particularly among high-risk populations, such as individuals with HIV.

BACKGROUND: Tocilizumab, an IL-6 receptor antagonist, may prevent functional impairments in critically ill patients by attenuating the cytokine storm. This study investigated a potential effect of tocilizumab on preventing functional impairments in patients with severe coronavirus infection 2019 (COVID-19). METHODS: In a multicenter prospective observational study, patients with COVID-19 ≥ 20 years requiring mechanical ventilation admitted to the intensive care unit between April 2021 and September 2021 and discharged alive were followed for one year. A self-administered questionnaire on sequelae and functional impairments was mailed in August 2022, and data were collected. A multivariate logistic regression was used to assess the impact of tocilizumab on physical function, mental health, and Long COVID. RESULTS: Of 157 analyzed patients, 41 received tocilizumab. The tocilizumab group had more severe illness, but a lower prevalence of physical impairment (17.1 % vs. 23.3 %, p = 0.41) and mental disorders (19.5 % vs. 39.7 %, p = 0.009) than the non-tocilizumab group. The prevalence of Long COVID was higher in the tocilizumab group (92.7 % vs. 80.2 %, p = 0.06), whereas fatigue/malaise was significantly lower (19.5 % vs. 37.1 %, p = 0.039). Adjusted odds ratios (95 % confidence interval) for physical impairment, mental disorders, and Long COVID with tocilizumab were 0.70 (0.2-2.1), 0.40 (0.16-1.01), and 2.94 (0.7-12.3), respectively, with no significant difference. CONCLUSIONS: Tocilizumab was associated with a lower prevalence of physical impairment and mental disorders at 1 year in patients with severe COVID-19. Furthermore, Long COVID had a weaker impact on physical and cognitive functions.

BACKGROUND: Research on the effectiveness of Japan's national action plan on antimicrobial resistance, including among individuals with HIV, remains scarce. OBJECTIVES: To evaluate the impact of policies on antibiotic prescription practices. METHODS: Outpatient oral antibiotic prescription data from 2012 to 2020 were extracted from a national claims database comprising >98% of the Japanese population. Prescription rates were stratified according to antibiotic class, diagnosis and HIV status. An interrupted time-series analysis was performed to assess the impact of the national action plan. RESULTS: An average of 129,989,400 prescriptions were issued annually (1024 per 1000 population-years). Between 2012 and 2020, the oral antibiotic prescription rate decreased by 54%. The prescription rate showed a significant downward trend post-intervention (additional annual reduction in incidence rate ratio, 0.889; 95% confidence interval, 0.889-0.990). However, broad-spectrum antibiotics (third-generation cephalosporins, macrolides and fluoroquinolones) remained prevalent, comprising 84.7% and 71.4% of prescriptions in 2012 and 2020, respectively. Antibiotic prescriptions during outpatient visits for pharyngitis, sinusitis, bronchitis and viral upper respiratory infections decreased significantly (rate ratios = 0.66, 0.76, 0.51 and 0.49, respectively). The antibiotic prescription rate was ∼2.5-fold higher in individuals with HIV than in those without. CONCLUSIONS: Antibiotic prescription rates significantly decreased following the implementation of the national action plan. However, a sharp decline in 2020, likely due to the coronavirus disease pandemic, requires continued rebound monitoring. Reducing broad-spectrum oral antibiotic overuse remains a critical focus.