Electronic health record nested pragmatic randomized controlled trial of a reminder system for serum lithium level monitoring in patients with mood disorder: KONOTORI study protocol

Background: The weaknesses of classical explanatory randomized controlled trials (RCTs) include limited generalizability, high cost, and time burden. Pragmatic RCTs nested within electronic health records (EHRs) can be useful to overcome such limitations. Serum lithium monitoring has often been underutilized in real-world practice in Japan. This trial aims to evaluate the effectiveness of the EHR-nested reminder system for serum lithium level monitoring in the maintenance of therapeutic lithium concentration and in the improvement of the quality of care for patients on lithium maintenance therapy. Methods: The Kyoto Toyooka nested controlled trial of reminders (KONOTORI trial) is an EHR-nested, parallel-group, superiority, stratified, permuted block-randomized controlled trial. Screening, random allocation, reminder output, and outcome collection will be conducted automatically by the EHR-nested trial program. Patients with a mood disorder taking lithium carbonate for maintenance therapy will be randomly allocated to the two-step reminder system for serum lithium monitoring or to usual care. The primary outcome is the achievement of therapeutic serum lithium concentration between 0.4 and 1.0 mEq/L at 18 months after informed consent. Discussion: The KONOTORI trial uses EHRs to enable the efficient conduct of a pragmatic trial of the reminder system for lithium monitoring. This may contribute to improved quality of care for patients on lithium maintenance therapy. Trial registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000033633. Registered on 3 July 2018

Intensive care unit versus high-dependency care unit admission on mortality in patients with septic shock: a retrospective cohort study using Japanese claims data

[Background] Septic shock is a common and life-threatening condition that requires intensive care. Intensive care units (ICUs) in Japan are classified into ICUs and high-dependency care units (HDUs), depending on presence of full-time certified intensivists and the number of assigned nurses. Compared with other developed countries, there are fewer intensive care beds and certified intensivists in Japan; therefore, non-intensivists often treat patients with septic shock in HDUs. It is unknown where we should treat patients with septic shock because no studies have compared the clinical outcomes between ICU and HDU treatment. This study aimed to elucidate which units should admit patients with septic shock by comparing mortality data and resource use between ICU and HDU admissions. [Methods] In this retrospective cohort study, we used a nationwide Japanese administrative database to identify adult patients with septic shock who were admitted to ICUs or HDUs between January 2010 and February 2021. The patients were divided into two groups, based on admittance to ICU or HDU on the day of hospitalization. The primary outcome was 30-day all-cause mortality adjusted for covariates using Cox regression analyses; the secondary outcomes were the length of ICU or HDU stay and length of hospital stay. [Results] Of the 10, 818 eligible hospitalizations for septic shock, 6584 were in the ICU group, and 4234 were in the HDU group. Cox regression analyses revealed that patients admitted to the ICUs had lower 30-day mortality (adjusted hazard ratio: 0.89; 95% confidence interval: 0.83–0.96; P = 0.005). Linear regression analyses showed no significant difference in hospital length of stay or ICU or HDU length of stay. [Conclusions] An association was observed between ICU admission and lower 30-day mortality in patients with septic shock. These findings could provide essential insights for building a more appropriate treatment system

Association of short term exposure to Asian dust with increased blood pressure

Air pollution causes hypertension, cardiovascular disease, and mortality. Asian dust (AD) reportedly induces asthma or acute myocardial infarction along with air pollution, but its impact on blood pressure (BP) is unknown. We investigated the association between short-term AD exposure and BP fluctuations in 300, 952 individuals whose BP was measured during April 2005–March 2015 and divided them into AD and non-AD groups based on visitation for AD-related events. AD’s occurrence, air pollutants’ concentration (suspended particulate matter, SO2, NO2, photochemical oxidants), and meteorological variables (mean ambient temperature, relative humidity) were obtained from a monitoring station; AD events correlated with decreased visibility (< 10 km). We observed 61 AD days, with 3897 participants undergoing medical check-ups. Short-term AD exposure at lag day-0 was significantly associated with higher systolic BP (SBP), diastolic BP (DBP), and pulse rate (PR) risk (β = 1.85, 95% confidence interval (CI) 1.35–2.35 for SBP, β = 2.24, 95% CI 1.88–2.61 for DBP, β = 0.52, 95% CI 0.14–0.91 for PR) using multi-pollutant model. Population-attributable fractions exposed to AD were 11.5% for those with elevated SBP (SBP ≥ 120 mmHg) and 23.7% for those with hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). This study showed a strong association between short-term AD exposure and increased SBP and DBP

Appropriateness of Percutaneous Coronary Intervention Performed by Japanese Expert Operators in Patients With Chronic Total Occlusion

Background: The appropriateness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions has rarely been investigated. Methods and Results: The Japanese CTO-PCI Expert Registry enrolled consecutive patients undergoing CTO-PCI carried out by highly experienced Japanese CTO specialists who performed more than 50 CTO-PCIs per year and 300 CTO-PCIs in total. This study included patients undergoing CTO-PCI between January 2014 and December 2019. The appropriateness, trends, and differences among the procedures performed by the operators using the 2017 appropriate use criteria were analyzed. Furthermore, we performed a logistic regression analysis to assess whether the appropriateness was associated with in-hospital major adverse cardiovascular and cerebrovascular events (MACCE). Of the 5, 062 patients who underwent CTO-PCI, 4, 309 (85.1%) patients who did not undergo the non-invasive stress test were classified as having no myocardial ischemia. Of the total cases, 3, 150 (62.2%) were rated as “may be appropriate, ” and 642 (12.7%) as “rarely appropriate” CTO-PCI cases. The sensitivity analyses showed that the number (%) of “may be appropriate” ranged from 4, 125 (57.8%) to 4, 744 (66.4%) and the number of “rarely appropriate” ranged from 843 (11.8%) to 970 (13.6%) among best and worst scenarios. Conclusions: In a large Japanese CTO-PCI registry, approximately 13% of CTO-PCI procedures were classified as “rarely appropriate”. Substantial efforts would be required to decrease the number of “rarely appropriate” CTO-PCI procedures

Effect of Regular Exercise and Functional Beverages on Changes in Body Weight and Waist Circumference in Healthy Japanese Subjects

Background and objectives: The effects on anthropometry of several lipid-related foods for specified health uses (FOSHU) approved in Japan are not well known. We examined the effects of regular exercise and lipid-related FOSHU beverages on changes in body weight (BW) and waist circumference (WC) among factory and office workers. Materials and Methods: A total of 3002 subjects aged 20 years or older (2497 men and 505 women) received health check-ups in 2015 and 2016 and completed a lifestyle questionnaire. The association between regular exercise or lipid-related FOSHU beverage intake and changes in BW or WC were evaluated using trend test and linear regression analysis. Results: Regular exercise (&ge;1/week) was reported by 774 subjects (25.8%), and regular consumption of lipid-related FOSHU beverages (&ge;1/week) was reported by 1168 subjects (38.9%). The significant association between lipid-related FOSHU beverage intake and changes in BW was only observed among subjects with regular exercise (p for trend = 0.042). In the multivariable analysis, sex, older age, baseline weight, baseline body mass index (BMI), and regular exercise behavior were significantly associated with smaller changes in BW (p &lt; 0.05). In WC, only the baseline values of WC and BMI were associated with one-year changes of WC. Conclusions: The combination of regular exercise and lipid-related FOSHU may be effective in maintaining BW

TCP Transcription Factors Regulate the Activities of ASYMMETRIC LEAVES1 and miR164, as Well as the Auxin Response, during Differentiation of Leaves in Arabidopsis[C][W]

This work examines the regulatory signaling for leaf differentiation by identifying the target genes of TEOSINTE BRANCHED1, CYCLOIDEA, and PCF (TCP) transcription factors in Arabidopsis. It identifies genetically redundant and differentially regulated pathways for balancing the differentiated and undifferentiated fates in leaf development