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Abstract Background While numerous studies have reported associations between low dietary potassium intake and adverse clinical outcomes, methods to estimate potassium intake, mainly self-reported dietary measures and urinary potassium excretion, entail certain limitations. Self-reported measures are subject to underreporting and overreporting. Urinary potassium excretion is affected by multiple factors including renal function. Revealing the degree of bias inherent in these measures would help accurately assess potassium intake and its association with disease risk. We aim to summarize evidence on the strength of the associations between potassium intake estimated from 24-h urinary potassium excretion and potassium intake estimated from self-reported dietary measures or objective quantification methods in populations with different kidney function levels and age groups. We also aim to identify factors that affect the association strength. Methods We will search for potentially eligible studies that examined associations between self-reported potassium intake, 24-h urinary potassium excretion, and objectively quantified potassium intake, using MEDLINE (PubMed), Embase, Web of Science, and Scopus. Studies on children, adolescents, adults, and the elderly are eligible. Studies of patients on dialysis will be excluded. Collective study results, including a meta-analysis, will be synthesized if an adequate number of studies examining similar dietary potassium intake estimation methods are found. Analyses will be performed separately according to age groups and renal function. For the meta-analysis, fixed-effects or random-effect models will be employed depending on the degree of study heterogeneity to combine across studies the correlation coefficient, ratio, or standardized mean difference for potassium intake, comparing dietary potassium intake based on self-reported or objectively quantified methods and intake based on 24-h urinary potassium excretion. The degree of heterogeneity among included studies will be examined by calculating I 2 statistics. To investigate sources of study heterogeneity, random-effects meta-regression analyses will be performed. Discussion Revealing the strength of the association between dietary and urinary measures in populations with different levels of kidney function and age groups will enhance researchers’ and clinicians’ ability to interpret studies that utilize these measures and help establish a more solid evidence base for the role of potassium intake in changing chronic disease risk. Identifying factors that modify the associations between these measures may aid in developing predictive models to estimate actual potassium intake. Systematic review registration PROSPERO CRD42022357847.

Background: Methamphetamine use is related to severe health, social, and criminal challenges. However, there is limited evidence regarding the factors associated with the recurrence of drug use among individuals who have used methamphetamine, particularly within populations involved in the criminal justice system. This study aimed to identify predictors of illicit drug use at a one-year follow-up among males in Japan who have used methamphetamine and are involved in the criminal justice system. Methods: The study participants were adult males on probation due to methamphetamine use or possession and were involved in a community-based program. The participants were recruited early in their probation period and participated in telephone-based surveys conducted by mental health center staff. We analyzed one-year follow-up data to investigate the recurrence rate of illicit drug use and associated risk factors using multiple logistic regression. Results: Out of 234 participants, 27 (11.5 %) used illicit drugs during the one-year follow-up period. After adjusting for demographic characteristics, severity of drug use, type of probation, and use of treatment for substance use disorders, the use of social welfare services (OR = 2.78) and a lack of trustworthy relationships (OR = 3.17) were significantly associated with recurrence of illicit drug use. Conclusions: This study suggested that individuals facing challenges in maintaining stable living conditions and building trustworthy relationships were more likely to return to drug use early in their probation period. Comprehensive and tailored support focused on social stabilization and relationship-building is recommended to aid recovery in males who have experienced methamphetamine use.

Abstract Background Exposure assessment is integral to the diagnosis of hypersensitivity pneumonitis (HP). Although the clinical relevance of exposed antigens is essential for the assessment, many of the previous guidelines or reports have only evaluated simple exposure histories or immunological tests. To overcome this problem, the Exposure Assessment Form (EAF) was developed as an assessment tool for classifying the exposure grade from G0 to G4. The EAF was modified from the description in the Japanese clinical practice guide 2022 for HP published by the Japanese Respiratory Society. Methods One hundred and seventy-two consecutive patients with interstitial lung disease who underwent multidisciplinary discussion (MDD) at our hospital were retrospectively examined. We assessed whether the use of the EAF improved the diagnostic performance of the international guideline of HP. We also evaluated whether the exposure grade affected the prognosis of HP. Results Even when a HP diagnosis was made with a confidence of 70% or higher according to the international guideline, less than half of these cases resulted in a final diagnosis of HP when the exposure grades were lower than G3. When the result of the EAF was integrated into the exposure definition of the international guideline, the specificity of the diagnostic performance improved, while sensitivity was maintained. Furthermore, HP patients with an exposure grade of G3 or higher showed a tendency to take a longer time to initiate medication. Conclusions This is the first study to evaluate the clinical relevance of possible antigens using the EAF. Assessing the exposure grade prevents overdiagnosis and improves the diagnostic performance of the international guideline.

Abstract Background Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. Methods This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. Results The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19–2.63], p = 0.005 and 1.97 [1.02–3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14–0.52], p

Physical function trajectory (PFT) is associated with mortality and hospitalization risks. We aimed to identify and compare the PFTs of newly admitted high-functioning older adults during their first six months at long-term care (LTC) facilities. In this multicenter retrospective cohort study, we included newly admitted high-functioning older adults (Barthel index > 60) from 47 Japanese LTC facilities. The primary outcome was physical function changes after admission. Data were collected from the Long-Term Care Information System for Evidence (LIFE), which monitored LTC facility residents’ function between 1 January 2021 and 31 January 2022. A group-based trajectory model and binomial logistic regression analyses were applied to identify and compare residents’ PFTs. Among the 718 residents included, the average age was 85.69 years and 64.5% were female. PFTs were classified as maintenance (66.0%), improvement (9.5%), slight decline (16.6%), and large decline (7.9%). The improvement group had significantly fewer residents who expressed a lack of interest in daily activities (odds ratio (OR) 0.45; 95% confidence interval (CI) 0.21–0.97) compared to the maintenance group. The large decline group had significantly more residents with a low BMI at admission (OR 2.42; 95% CI 1.29–4.55) and residents who did not use dentures (OR 0.49; 95% CI 0.26–0.95), compared to the maintenance group. Considering future PFTs may aid the development of care plans and the provision of appropriate interventions. Moreover, utilizing existing data has the potential to maintain residents’ physical independence and enhance the quality of care without burdening residents themselves or staff.

ABSTRACT: Background: Treatment for pyogenic spondylitis tends to be prolonged; however, few studies have examined the factors associated with the time required for infection control. Therefore, we analyzed a consecutive cohort of patients to identify factors associated with the time required to control infection in pyogenic spondylitis. This study aimed to clarify the factors linked to the duration necessary for achieving infection control in cases of pyogenic spondylitis, using C-reactive protein (CRP) normalization as an indicator. Methods: In this retrospective observational study, we investigated 108 patients diagnosed with pyogenic spondylitis. We evaluated the number of days from the first visit to CRP normalization; for cases wherein CRP did not normalize, the number of days to the date of final blood sampling was evaluated. In the present study, infection control in pyogenic spondylitis was defined as a CRP falling within the normal range (≤0.14 mg/dL). We performed univariate and multivariate Cox regression analyses to identify various factors associated with the time required for CRP normalization in pyogenic spondylitis. Results: The mean time required for CRP normalization was 148 days. Univariate Cox regression analysis showed that the serum creatinine level, estimated glomerular filtration rate (eGFR), lymphocyte percentage, neutrophil percentage, CRP level, CRP-albumin ratio, and neutrophil-to-lymphocyte ratio were significantly associated with the time required to control infection. Multivariate Cox regression analysis showed that a higher neutrophil percentage, diabetes mellitus, and a lower eGFR were the independent factors associated with a longer infection control time. Conclusions: We found that a higher neutrophil percentage, diabetes mellitus, and a lower eGFR were significantly associated with a longer time for CRP normalization in pyogenic spondylitis. These findings may help identify patients with pyogenic spondylitis who are at a high risk for an extended infection control period.

Abstract Background The potential for developing frailty exists in middle‐aged and older adults. While obesity and metabolic syndrome (MetS) increase the risk of frailty in older adults, this relationship remains unclear in middle‐aged adults, who are prone to developing lifestyle‐related diseases. Objective To examine the effect of overweight/obesity and MetS on frailty development in middle‐aged and older Japanese adults using real‐world data. Methods This nationwide cohort study used exhaustive health insurance claims data of 3,958,708 Japanese people from 2015 to 2019 provided by the Japan Health Insurance Association. Participants aged ≥35 and

Abstract Background It is clinically important to predict difficulty in short-term liberation from veno-venous extracorporeal membrane oxygenation (V-V ECMO) in patients with severe acute respiratory distress syndrome (ARDS) at the time of initiation of the support. The aim of this study was to identify the characteristics of pulmonary opacities on chest CT that is associated with difficulty in short-term liberation from V-V ECMO (

Abstract Age-based bodyweight estimation is commonly used in pediatric settings, but pediatric ICU patients often have preexisting comorbidity and resulting failure to thrive, hence their anthropometric measures may be small-for-age. Accordingly, age-based methods could overestimate bodyweight in such settings, resulting in iatrogenic complications. We performed a retrospective cohort study using pediatric data (aged

Abstract Prenatal recognition of coarctation of the aorta (CoA) may improve neonatal survival and reduce morbidity. However, prenatal diagnosis of CoA remains challenging, with relatively high false-positive and false-negative rates. This study aimed to identify a novel formula based on fetal echocardiographic measures to predict prenatal identification of CoA. A retrospective comparison on the echocardiographic evaluation of 30 patients with suspected CoA between May 2016 and April 2021 was performed. The patients were divided into a postnatal surgical intervention group (n = 13) and a non-intervention group (n = 17). The measurements that showed significant differences were aortic isthmus diameter Z-score (p

Background: Japan has witnessed an unusual increase in the number of suicides among women during the coronavirus disease 2019 pandemic. An analysis is required to identify the influencing factors during the pandemic and develop new measures for preventing suicides. Methods: Data on the number of monthly suicides were collected from the National Police Agency of Japan. The expected number of suicides among women during the pandemic was estimated using a time-series model based on pre-pandemic data, considering year-to-year trends. The observed-to-expected (O/E) ratio of suicides was estimated from March 2020 to October 2021 using job status, suicide motive, and age. Results: The number of suicides among women in Japan increased beyond the expected number until October 2021. The O/E ratio based on job status, suicide motive, and age (except self-employed, unknown job status, and women aged ≥80 years) was significantly above 1.0 from March–December 2020, and the increase in suicides continued in almost all categories in 2021. Conclusion: Although several reasons were reported for increased suicides among women in Japan during the pandemic (eg, economic downturn, financial instability, and loneliness), suicides increased irrespective of job status, suicide motive, or age. Comprehensive measures to prevent suicide might have been important during the pandemic, instead of limiting interventions to the reported specific population.

Introduction While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting.Methods and analysis The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay.Ethics and dissemination Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals.Trial registration number The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022.Protocol version 28 March 2023, version 4.0.

ABSTRACT: Background: Due to its association with bone metabolic status and muscle strength/mass, vitamin D deficiency has the potential to affect neurological symptom recovery after surgery for degenerative cervical myelopathy (DCM). However, few studies have investigated the effects of vitamin D deficiency (serum 25(OH)D

Abstract Background Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. Methods A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80–85 mmHg (high-target) and 65–70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients’ condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. Discussion The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. Trial registration UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

Abstract The prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The study objectives were to investigate the prognostic effects of ALC and ANC in POP patients, and to evaluate the time courses of ALC and ANC during hospitalization. This post-hoc analysis of a single-center prospective observational study evaluated consecutive POP patients, and comparatively analyzed community-acquired pneumonia (CAP) patients to highlight features of POP. In total, 228 POP patients and 1027 CAP patients were assessed. Severe lymphopenia (ALC 7500 cells/μL) was associated with better survival, whereas CAP patients with neutrophilia tended to have a lower survival rate. Prolonged lymphopenia and delayed increase in neutrophils were characteristic time-course changes of non-survivors in POP. The time courses of ALC and ANC between survivors and non-survivors in POP trended differently from those in CAP. Our study showed that ALC and ANC at pneumonia diagnosis can serve as prognostic factors in POP patients. Differences in time-course changes of ALC and ANC between survivors and non-survivors may provide important information for future immunological research in pneumonia.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Background:. Although postpartum hair loss is believed to be common, there is little reliable information. Objective:. We sought to examine the factors that were associated with postpartum hair loss and to elucidate factors correlated with its pathogenesis. Methods:. We carried out a questionnaire-based cross-sectional study. The study participants were women who delivered at 2 facilities and filled the questionnaire 10–18 months after delivery. The survey questionnaire included baseline characteristics, pregnancy details, delivery, childcare, and extent of postpartum hair loss. We divided participants into 2 groups according to the absence or presence of postpartum hair loss and performed logistic regression analyses. Results:. A total of 331 (21.0%) responses were analyzed; among these 304 (91.8%) women had postpartum hair loss. The average time for the start, peak, and end of hair loss was 2.9, 5.1, and 8.1 months, respectively. Women with hair loss had an earlier time of delivery, a lower birth weight, a higher preterm labor rate, and longer-term breastfeeding. Logistical regression analyses revealed that longer-term breastfeeding and preterm labor were independent predictors of postpartum hair loss. The adjusted odds ratio for postpartum hair loss in women who ended breastfeeding 6–12 months postpartum versus those who ended it after 12 months or more was 5.96 (95% confidence interval [CI] [1.68, 21.09]) and 6.37 (95% CI [1.95, 20.76]) compared with those who stopped breastfeeding within 6 months postpartum. Limitations:. Finer details such as pregnancy complications and delivery information may not be accurate since all results are based on questionnaire responses. There may be a sampling bias because women who suffer from postpartum hair loss may tend to participate more frequently. Conclusion:. Over 90% of women experienced postpartum hair loss. Our data show that long-term breastfeeding and preterm labor correlate with postpartum hair loss.

Abstract Background For patients admitted to the intensive care unit (ICU) with sepsis, mobilization therapy during ICU stay can improve their outcomes during and after the ICU stay. However, little is known about the optimal timing of introducing mobilization therapy. Methods This is a retrospective cohort study using data from a tertiary medical center in Japan during 2013–2017. We included patients aged ≥ 18 years who were admitted to the ICU with sepsis based on the Sepsis-3 criteria. We defined early mobilization (EM) as the rehabilitation at the level of sitting on the edge of the bed or more within the first 3 days of the patients’ ICU stay. Patients were divided into the EM and non-EM groups. The primary outcomes were in-hospital mortality and ambulatory dependence at hospital discharge. We estimated the effects of EM by stabilized inverse probability weighting (sIPW). We then tested alternative definitions of EM by changing the cutoff in days to mobilization by 1-day increments from 2 to 7 days to investigate the optimal timing of mobilization. Results Our study sample consisted of a total of 296 septic patients, including 96 patients in the EM group and 200 patients in the non-EM group. In the sIPW model, the adjusted OR for in-hospital mortality in the EM group compared to the non-EM group was 0.22 [95% CI 0.06–0.88], and the adjusted OR for ambulatory dependence at the hospital discharge was 0.24 [95% CI 0.09–0.61]. When alternative definitions of EM were tested, patients who achieved mobilization within the first 2–4 days of their ICU stays had better outcomes. Conclusions Achieving mobilization within the first 3 days of ICU stay was significantly associated with better outcomes. Patients with sepsis might benefit most from achieving mobilization within 2–4 days. Further studies are warranted to validate the findings.

IntroductionHigh stress at work is associated with negative health outcomes for workers, making stress prevention a critical challenge. Overtime work is an influential stress factor. This study, therefore, aimed to longitudinally evaluate how stress increased depending on changes in working hours among Japanese white-collar workers.MethodsWe targeted 3,874 participants who were full-time workers and were recognized as having low stress in a web-based cohort in 2018 (T1) and 2019 (T2). We performed univariate and multivariate logistic regression with the following variables: years of experience, years of education, medical background, income, and roommates.ResultsWe observed a greater increase in stress among female who worked 41–50 h per week at T1 and more than 50 hours per week at T2, and those who worked more than 50 h per week at T1 and 35–40/41–50 h per week at T2, compared to those who worked 41–50 h per week both at T1 and T2, with odds ratios (ORs) and 95% confidence intervals (95% CI) of OR = 2.09, 95% CI (1.18, 3,70); OR =1.86, 95% CI (1.14, 3.03), respectively. However, no association between change in working hours and stress was found among male.DiscussionThese results show that reducing stress requires decreasing working hours as well as identifying factors that lead to high stress.

Abstract Background Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP. Methods Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study. Results The ALL-COP SCORE rule included albumin ( 45 mmHg, 2 points), HCO3 − ( 2/3, 2 points; 1/2–2/3, 1 point). Patients with 4–5, 6–7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity. Conclusions ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points. Trial registration This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837.

Background: After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined. Methods: Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level. Results: Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52–2.59), 0.55 (95% CI, 0.31–0.97), 1.05 (95% CI, 0.79–1.40), and 1.24 (95% CI, 0.89–1.74). Conclusion: There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016–2017) in Fukushima Prefecture.

Objectives: As romosozumab has both bone anabolic and antiresorptive effects, it is not clear which patient groups are more likely to have decreased calcium concentrations when treated with romosozumab. The aim of this study was to investigate the impact of romosozumab treatment on serum calcium concentration in patients with osteoporosis with a high risk of fractures and identify factors that might be associated with, or even predict, a fluctuation in calcium concentration upon romosozumab administration. Materials and methods: In total, 47 patients were included in this retrospective study. We performed a Wilcoxon signed-rank test to identify differences in the calcium concentration before and 1 month after romosozumab initiation. Associations between baseline variables and changes in serum calcium concentration were investigated with a multiple-linear regression model using a forward-backward stepwise procedure. Results: Romosozumab administration reduced the serum calcium concentration by an average of 3.1 % after 1 month. No patient complained of symptoms of hypocalcemia during the first month after treatment. Univariate regression analysis showed that age and calcium concentration were significantly associated with the decrease in serum calcium concentrations by romosozumab administration. In addition, stepwise regression analysis identified age and calcium concentrations as independent factors associated with the decrease in calcium concentration by romosozumab. Conclusion: Romosozumab administration caused a modest but significant decrease in serum calcium concentration. Older age and higher baseline calcium concentrations were associated with a greater decrease in calcium concentrations by romosozumab administration. Although the likelihood of severe hypocalcemia from romosozumab administration may be low, physicians prescribing romosozumab to patients with osteoporosis should be aware of the symptoms of hypocalcemia and promptly evaluate calcium levels if patients complain of these symptoms.

Late-life depression is one of the most common mental illnesses that cause serious consequences, but the majority do not reach out for mental health services and relapses are common. The present study investigated profiled similarity of older adults' social networks in terms of depressive symptoms. In 2017, we distributed questionnaires inquiring about confidants in the community, depressive symptoms based on the 15-item Geriatric Depression Scale (GDS-15), and demographic and functional characteristics to all the community-dwelling older adults under the national insurance system in Wakuya City (Miyagi prefecture, Japan). Applying the Exponential Random Graph Model, we estimated the likelihood of a confidant relational tie by the similarity of overall and specific depressive symptoms within 217,470 potential ties among 660 respondents eligible for analysis. The overall depressive symptom homophily was marginally significant (p < 0.10), indicating that the likelihood of a confidant relational tie between two community-dwelling older adults was decreased by 5%, with one point increase in their difference in the total number of depressive symptoms (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.90–1). Focusing on specific domains of depressive symptoms, we found significant apathy homophily (p < 0.05) but no significant suicidal ideation of homophily. The results indicated that there is a 19% decrease in the likelihood of a confidant relational tie between two community-dwelling older adults by one point increase in their difference in the total number of apathy symptoms (OR, 0.81; 95%CI, 0.67–0.98) but no change by increasing the difference in their total number of suicidal ideation symptoms (OR, 1; 95%CI, 0.87–1.14). These findings suggest depressive symptom homophily, particularly with respect to apathy domains, in confidant social networks of community-dwelling older adults, and the importance of network intervention in preventing late-life depression.

Background: Evidence for the risk and incidence of anticonvulsant-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Japan is scarce. Methods: We conducted a matched case–control study using a large-scale Japanese claims database. SJS/TEN cases were identified using a claims-based algorithm developed in a previous study (sensitivity 76.9%, specificity 99.0%). Conditional logistic regression with Firth's bias correction to address an issue of rare events was used to estimate odds ratios (ORs) for SJS/TEN for each anticonvulsant use (90 days before the index date) versus non-use. 90-day cumulative incidence of SJS/TEN per 100,000 new users was calculated for 33 anticonvulsants. Causality between anticonvulsant use and SJS/TEN in each exposed case was assessed using the algorithm of drug causality for epidermal necrolysis (ALDEN) score. Results: From 5,114,492 subjects, we selected 71 SJS/TEN cases and 284 controls. We observed significantly increased ORs for SJS/TEN among new users of carbamazepine (OR 68.00) and lamotrigine (OR 36.00) with ALDEN scores of “probable” or higher. Cumulative incidence of SJS/TEN was 93.83 for carbamazepine and 84.33 for lamotrigine. One case newly exposed to phenytoin which developed SJS/TEN was rated “unlikely” in ALDEN causality, resulting in cumulative incidence of 66.27. Cumulative incidence of SJS/TEN was 25.23 for levetiracetam, 7.52 for clonazepam, and 1.23 for diazepam, but their ALDEN scores were “very unlikely”. Conclusions: This study is the first to document the differential risk of SJS/TEN for anticonvulsants in a real-world setting in Japan. Exposure to carbamazepine and lamotrigine was associated with an increased risk of SJS/TEN.

Abstract In sepsis-associated coagulopathies and disseminated intravascular coagulation, relative platelet reductions may reflect coagulopathy severity. However, limited evidence supports their clinical significance and most sepsis-associated coagulopathy criteria focus on the absolute platelet counts. To estimate the impact of relative platelet reductions and absolute platelet counts on sepsis outcomes. A multicenter retrospective observational study was performed using the eICU Collaborative Research Database, comprising 335 intensive care units (ICUs) in the United States. Patients with sepsis and an ICU stay > 2 days were included. Estimated effects of relative platelet reductions and absolute platelet counts on mortality and coagulopathy-related complications were evaluated. Overall, 26,176 patients were included. Multivariate mixed-effect logistic regression analysis revealed marked in-hospital mortality risk with larger platelet reductions between days one and two, independent from the resultant absolute platelet counts. The adjusted odds ratio (OR) [95% confidence intervals (CI)] for in-hospital mortality was 1.28[1.23–1.32], 1.86[1.75–1.97], 2.99[2.66–3.36], and 6.05[4.40–8.31] for 20–40%, 40–60%, 60–80%, and > 80% reductions, respectively, when compared with a

Abstract Background Fibrotic hypersensitivity pneumonitis (HP) is a chronic interstitial lung disease caused by allergic responses to repeated exposures to a causative antigen. Therapeutic evidence of the use of corticosteroids to treat fibrotic HP remains lacking, although corticosteroids are recognized as a major treatment option. The purpose of this study was to evaluate the efficacy of corticosteroid treatment in patients with fibrotic HP in a propensity score-matched cohort. Methods A retrospective review of the medical records from 2005 to 2019 in a single center was conducted, and 144 patients with fibrotic HP were identified. Semiquantitative scores for lung abnormalities on HRCT were evaluated. Patients who received (PDN group) and did not receive (non-PDN group) corticosteroid treatment were matched using a propensity score method. Survival rates, serial changes in pulmonary function and annual changes in HRCT scores were compared in the matched cohort. Results In the matched analysis, 30 individuals in the PDN group were matched with 30 individuals in the non-PDN group, the majority of whom had ILD without extensive fibrosis. The survival rate was significantly better in the PDN group (P = 0.032 for the stratified Cox proportional hazards model; HR, 0.250). The absolute changes in FVC at 6, 12, and 24 months from baseline were significantly better in the PDN group. Fewer patients in the PDN group experienced annual deterioration, as reflected in the HRCT score, due to ground-glass attenuation, consolidation, reticulation, traction bronchiectasis and honeycombing. Conclusion We demonstrated that corticosteroids improved survival and slowed fibrotic progression in a matched cohort, the majority of whom had ILD without extensive fibrosis. Fibrotic HP with less severe fibrosis may benefit from corticosteroid treatment. We propose that the early initiation of corticosteroids should be considered for fibrotic HP when worsening fibrosis is observed.

Abstract Background Anterior decompression with fusion (ADF) has often been performed for degenerative cervical myelopathy (DCM) in patients with poor cervical spine alignment and/or anterior cord compression. We aimed to identify clinical and radiological predictors associated with neurological recovery after ADF. Methods This post-hoc analysis from a prospective multicenter study included patients who were scheduled for ADF for DCM. The patients who received other surgeries (laminoplasty, posterior decompression and fusion) were excluded. The associations between baseline clinical and radiographic variables (age, sex, body mass index, etiology, cervical lordosis, range of motion, C7 slope, C2-7 sagittal vertical axis [SVA], thoracic kyphosis [TK], lumbar lordosis, sacral slope, SVA, pelvic tilt, T1 pelvic angle [TPA], the Japanese Orthopedic Association score for the assessment of cervical myelopathy [C-JOA], European Quality of Life Five Dimensions Scale [EQ-5D], Neck Disability Index [NDI], Physical Component Summary of the SF-36 [PCS], and Mental Component Summary of the SF-36) and the recovery rates as the outcome variables were investigated in the univariate regression analysis. Then, the independent predictors for increased recovery rates were evaluated using a stepwise multiple regression analysis. Results In total, 37 patients completed the 1 year follow-up. The recovery rate was significantly correlated with SVA (p = 0.001) and TPA (p = 0.03). Univariate regression analyses showed that age (Regression coefficient = − 0.92, p = 0.049), SVA (Regression coefficient = − 0.57, p = 0.004) and PCS (Regression coefficient = 0.80, p = 0.03) score were significantly associated with recovery rate. Then, a stepwise multiple regression analysis identified the independent predictors of recovery rate after ADF as TK (p = 0.01), PCS (p = 0.03), and SVA (p = 0.03). According to this prediction model, the following equation was obtained: recovery rate = − 8.26 + 1.17 × (TK) − 0.45 × (SVA) + 0.85 × (PCS) (p = 0.002, R 2 = 0.44). Conclusion Patients with lower TK, lower PCS score, and higher SVA were more likely to have poor neurological recovery after ADF. Therefore, patients with DCM and these predictors who undergo ADF should be warned about poor recovery and be required to provide adequate informed consent.

Abstract Background There is limited quantitative research on the effect of physician attire on patient–physician relationships. This study aimed to measure the influence of Japanese family physicians’ attire on the “human” aspects of medical care in terms of patient-perceived relational empathy. Methods This was a multicenter, prospective, controlled trial conducted in primary clinics in Japan. We explored the effects of family physician attire (white coat vs. casual attire) on patient-perceived empathy. Family physicians were allocated to alternate weeks of wearing a white coat or casual attire during consultations. Patients’ perceptions of physician empathy were evaluated using the self-rated Japanese Consultation and Relational Empathy (CARE) Measure. We used a linear mixed model to analyze the CARE Measure scores, adjusting for cluster effects of patients nested within doctor, age, and sex of patients, and doctors’ sex and years of clinical experience. We used the same method with Bonferroni adjustment to analyze patient sex differences in perceived empathy. Results A total of 632 patients of seven family physicians were allocated to white coat-wearing consultations (n = 328), and casual attire-wearing consultations (n = 304). There was no difference in CARE Measure scores between white coat and casual primary care consultations overall (p = 0.162). Subgroup analysis of patient sex showed that CARE Measure scores of male patients were significantly higher in the Casual group than in the White coat group (adjusted p-value = 0.044). There was no difference in female patient scores between White coat and Casual groups (adjusted p-value = 1.000). Conclusions This study demonstrated that physician attire (white coat or casual attire) in a primary care setting did not affect patient-perceived relational empathy overall. However, male patients of physicians wearing casual attire reported higher physician empathy. Although empathy cannot be reduced to simple variables such as attire, white coats may have a negative effect on patients, depending on the context. Family physicians should choose their attire carefully. Trial registration Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000037687 (Registered August 14, 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042749 ). The study was prospectively registered.

Background: Suicide amidst the coronavirus disease (COVID-19) pandemic is an important issue. In Japan, the number of suicides in April 2020 decreased by nearly 20% from that in 2019. To assess the impact of an infectious disease pandemic, excess mortality is often discussed. Our main purpose was evaluating excess mortality from suicide in Japan during the early pandemic period. Methods: We used data on suicides collected by the National Police Agency of Japan until June 2020. We estimated excess mortality during the early pandemic period (March–June 2020) using a time-series model of the number of suicides before the pandemic. A quasi-Poisson model was employed for the estimation. We evaluated excess mortalities by the categories of age and sex, and by prefecture. Results: No significant excess mortality was observed throughout the early pandemic; instead, a downward trend in the number of suicides for both sexes was noted. For males, negative values of excess mortalities below the lower bound of the 95% prediction interval were observed in April and May. All numbers of females during the period were included in the interval, and the excess mortalities in June were positive and higher than those in April and May. In Tokyo, the number of suicides was below the lower bound throughout the period. Conclusion: Our results suggest that various changes, such as communication, and social conditions amid the early COVID-19 pandemic induced a decrease in suicides in Japan. However, continuous monitoring is needed to evaluate the long-term effects of the pandemic on suicides.

ABSTRACT Excluding clinical trials, there is limited evidence on the effect of 12 months of romosozumab treatment on bone mineral density (BMD) increase in real‐world clinical practice because its use has only been approved recently. Thus, this study aimed to investigate the real‐world effect of 12 months of romosozumab treatment on BMD increase and identify factors that predict the rate of BMD increase after 12 months of romosozumab treatment. We retrospectively investigated 106 patients who completed a 12‐month romosozumab treatment for osteoporosis with a high risk of fractures at four hospitals from March 2020 to March 2022. The univariate and multiple regression analyses were performed to analyze the concurrent effects of various factors on the BMD increase after the 12‐month romosozumab treatment. After 1 year of treatment, the lumbar spine BMD increased by 14.6%, and femoral neck BMD increased by 5.1%. Univariate regression analysis found that male sex, high tartrate‐resistant acid phosphatase 5b (TRACP‐5b) value before romosozumab administration, absence of osteoporosis medications before romosozumab administration, and low baseline lumbar spine BMD were associated with the extent of lumbar spine BMD increase. Moreover, stepwise multiple regression analysis found that the TRACP‐5b value before romosozumab administration was a significant predictor of the rate of lumbar spine BMD increase after 1 year of romosozumab administration. In conclusion, our results demonstrated the effectiveness of the 12‐month romosozumab treatment for osteoporosis with a high risk of fractures and the TRACP‐5b value before romosozumab administration was a significant predictor of the rate of lumbar spine BMD increase after 1 year of romosozumab administration. Our findings could help establish more efficient treatment strategies for patients with osteoporosis at a high risk of fracture. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Abstract Background Detecting the geographical tendency for the presence of a disease or incident is, particularly at an early stage, a key challenge for preventing severe consequences. Given recent rapid advancements in information technologies, it is required a comprehensive framework that enables simultaneous detection of multiple spatial clusters, whether disease cases are randomly scattered or clustered around specific epicenters on a larger scale. We develop a new methodology that detects multiple spatial disease clusters and evaluates its performance compared to existing other methods. Methods A novel framework for spatial multiple-cluster detection is developed. The framework directly stands on the integrated bases of scan statistics and generalized linear models, adopting a new information criterion that selects the appropriate number of disease clusters. We evaluated the proposed approach using a real dataset, the hospital admission for chronic obstructive pulmonary disease (COPD) in England, and simulated data, whether the approach tends to select the correct number of clusters. Results A case study and simulation studies conducted both confirmed that the proposed method performed better compared to conventional cluster detection procedures, in terms of higher sensitivity. Conclusions We proposed a new statistical framework that simultaneously detects and evaluates multiple disease clusters in a large study space, with high detection power compared to conventional approaches.

Background: After the Fukushima Daiichi Nuclear Power Plant accident, a preliminary ultrasound-based screening for thyroid cancer was conducted to establish a baseline for subsequent evaluations. In this survey, we assessed the relationship between the proportion of non-examinees and characteristics of the target populations. Methods: After summarizing a regional difference of non-examinees among the population of 359,200 (primary evaluation) and 2,246 (confirmatory testing) individuals who were living in Fukushima Prefecture on March 11, 2011, we estimated odds ratios (ORs) for each characteristic, including age, sex, area of residence, and moving after the accident, based on the proportion of non-examinees for the primary examination and the confirmatory testing, using a multivariate logistic regression model. Results: The dataset included 64,117 non-examinees (primary evaluation) and 194 (confirmatory testing). The logistic regression result indicated that girls were not likely to be non-examinees compared to boys, with adjusted OR of 0.80 (95% confidence interval [CI], 0.78–0.81) for the primary evaluation. Odds were lowest for children 6–10 years old (OR 0.26; 95% CI, 0.25–0.27), and higher for those 11–15 years old (OR 1.28; 95% CI, 1.25–1.32) and over 16 years old (OR 5.30; 95% CI, 5.16–5.43) when compared to children 0–5 years old. Individuals residing in the western part of the prefecture showed higher ORs. There was a higher proportion of non-examinees among those who moved after the accident compared to those who did not in the primary evaluation (OR 1.72; 95% CI, 1.64–1.79). Conclusions: In addition to demographic characteristics, a change of residence could be a potential factor that influenced the proportion of non-examinees. Our results will help proper interpretation of reports and prospective management of the survey.

Abstract Background Little is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US). Methods We summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications. Results The proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for ‘general disorders and administration site conditions’ from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for ‘injury, poisoning, and procedural complications’ from the class of single psychiatric medication (OR = 2.8). Conclusions The main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results.

Purpose Although the understanding of the mechanisms of low back pain due to spinopelvic sagittal imbalance has strengthened, the understanding of the mechanisms of neck pain remains insufficient. Thus, this study aimed to identify the factors associated with preoperative and postoperative neck pain in patients with degenerative cervical myelopathy who underwent laminoplasty. Methods In this prospective multicenter study, we prospectively enrolled patients who were scheduled for laminoplasty for degenerative cervical myelopathy. The associations between different variables and the Numerical Pain Rating Scale (NRS) scores for neck pain were investigated using univariate and multiple linear regression models. Results In total, 92 patients were included in the current study. The univariate analysis showed that age, sex, cervical lordosis in neutral and extension, and thoracic kyphosis were significantly associated with the preoperative NRS score for neck pain; moreover, preoperative cervical lordosis in extension and range of motion and postoperative cervical lordosis in neutral, flexion, and extension were significantly associated with the postoperative NRS Scale score for neck pain. Stepwise multiple regression analysis showed that the independent factors contributing to preoperative neck pain were preoperative cervical lordosis in extension, sex, and age. The independent preoperative predictor and contributor to postoperative neck pain were preoperative cervical lordosis in extension and postoperative cervical lordosis in extension, respectively. Conclusions Cervical lordosis in extension showed significant association with neck pain in patients with degenerative cervical myelopathy. Therefore, when performing laminoplasty for patients with a low cervical lordosis in extension, attention should be paid to residual postoperative neck pain.

Introduction Sepsis is not only the leading cause of death in the intensive care unit (ICU) but also a major risk factor for physical and cognitive impairment and mental disorders, known as postintensive care syndrome (PICS), reduced health-related quality of life (HRQoL) and even mental health disorders in patient families (PICS-family; PICS-F). The ABCDEF bundle is strongly recommended to overcome them, while the association between implementing the bundle and the long-term outcomes is also unknown.Methods and analysis This is a multicentre prospective observational study at 26 ICUs. All consecutive patients between 1 November 2020 and 30 April 2022, who are 18 years old or older and expected to stay in an ICU for more than 48 hours due to sepsis or septic shock, are enrolled. Follow-up to evaluate survival and PICS/ PICS-F will be performed at 3, 6 and 12 months and additionally every 6 months up to 5 years after hospital discharge. Primary outcomes include survival at 12 months, which is the primary outcome, and the incidence of PICS defined as the presence of any physical impairment, cognitive impairment or mental disorders. PICS assessment scores, HRQoL and employment status are evaluated. The association between the implementation rate for the ABCDEF bundle and for each of the individual elements and long-term outcomes will be evaluated. The PICS-F, defined as the presence of mental disorders, and HRQoL of the family is also assessed. Additional analyses with data up to 5 years follow-up are planned.Ethics and dissemination This study received ethics approvals from Saiseikai Utsunomiya Hospital (2020-42) and all other participating institutions and was registered in the University Hospital Medical Information Network Clinical Trials Registry. Informed consent will be obtained from all patients. The findings will be published in peer-reviewed journals and presented at scientific conferences.Trial registration number UMIN000041433.

Background: Data regarding delivery of evidence-based care to critically ill patients in Intensive Care Units (ICU) during the COVID-19 pandemic is crucial but lacking. This study aimed to evaluate the implementation rate of the ABCDEF bundle, which is a collection of six evidence-based ICU care initiatives which are strongly recommended to be incorporated into clinical practice, and ICU diaries for patients with and without COVID-19 infections in ICUs, and to analyze the impact of COVID-19 on implementation of each element of the bundle and independent associated factors.Methods: A world-wide 1-day point prevalence study investigated the delivery of the ABCDEF bundle and ICU diary to patients without or with COVID-19 infections on 27 January 2021 via an online questionnaire. Multivariable logistic regression analysis with adjustment for patient demographics evaluated the impact of COVID-19 and identified factors in ICU administrative structures and policies independently associated with delivery.Results: From 54 countries and 135 ICUs, 1,229 patients were eligible, and 607 (49%) had COVID-19 infections. Implementation rates were: entire bundle (without COVID-19: 0% and with COVID-19: 1%), Element A (regular pain assessment: 64 and 55%), Element B (both spontaneous awakening and breathing trials: 17 and 10%), Element C (regular sedation assessment: 45 and 61%), Element D (regular delirium assessment: 39 and 35%), Element E (exercise: 22 and 25%), Element F (family engagement/empowerment: 16 and 30%), and ICU diary (17 and 21%). The presence of COVID-19 was not associated with failure to implement individual elements. Independently associated factors for each element in common between the two groups included presence of a specific written protocol, application of a target/goal, and tele-ICU management. A lower income status country and a 3:1 nurse-patient ratio were significantly associated with non-implementation of elements A, C, and D, while a lower income status country was also associated with implementation of element F.Conclusions: Regardless of COVID-19 infection status, implementation rates for the ABCDEF bundle, for each element individually and an ICU diary were extremely low for patients without and with COVID-19 infections during the pandemic. Strategies to facilitate implementation of and adherence to the complete ABCDEF bundle should be optimized and addressed based on unit-specific barriers and facilitators.

The spatial scan statistic is commonly used to detect spatial disease clusters in epidemiological studies. Among the various types of scan statistics, the flexible scan statistic proposed by Tango and Takahashi (2005) is one of the most promising methods to detect arbitrarily-shaped clusters. In this paper, we introduce a new R package, rflexscan (Otani and Takahashi 2021), that provides efficient and easy-to-use methods for analyses of spatial count data using the flexible spatial scan statistic. The package is designed for any of the following interrelated purposes: to evaluate whether reported spatial disease clusters are statistically significant, to test whether a disease is randomly distributed over space, and to perform geographical surveillance of disease to detect areas of significantly high rates. The functionality of the package is demonstrated through an application to a public-domain small-area cancer incidence dataset in New York State, USA, between 2005 and 2009.

Abstract Background Currently, the appropriate method of management of patients with refractory septic shock remains unclear. This study aimed to evaluate the factors associated with response to epinephrine in norepinephrine-refractory septic shock. Methods A retrospective single-center observational study was performed using data from adult patients (≥ 18 years old) admitted to our emergency and medical intensive care unit (ICU) from January 2014 to December 2017 who had received epinephrine to treat norepinephrine-refractory septic shock. The response was considered positive if there was increase in mean arterial pressure of 10 mmHg or decrease in arterial lactate level 3 h after epinephrine administration. Results Forty-one patients were included: 24 responders (59%) and 17 non-responders (41%). Responders showed higher rate of survival from shock (92% vs. 18%; P

Objectives:. To investigate implementation of evidence-based and supportive cares in ICUs, such as the ABCDEF, nutrition therapy, and ICU diary, for patients with coronavirus disease 2019 infection in ICUs and their association with ICU clinical practice and setting. Design:. A worldwide, 2-day point prevalence study. Setting:. The study was carried out on June 3, 2020, and July 1, 2020. A total of 212 ICUs in 38 countries participated. Clinicians in each participating ICU completed web-based online surveys. Patients:. The ICU patients with coronavirus disease 2019. Interventions:. None. Measurements and Main results:. The implementation rate for the elements of the ABCDEF bundle, other supportive ICU care measures, and implementation-associated structures were investigated. Data were collected for 262 patients, of whom 47.3% underwent mechanical ventilation and 4.6% were treated with extracorporeal membrane oxygenation. Each element was implemented for the following percentages of patients: elements A (regular pain assessment), 45%; B (both spontaneous awakening and breathing trials), 28%; C (regular sedation assessment), 52%; D (regular delirium assessment), 35%; E (early mobility and exercise), 47%; and F (family engagement and empowerment), 16%. The implementation of element E was 4% for patients on mechanical ventilation and 8% for patients on extracorporeal membrane oxygenation. Supportive care, such as protein provision throughout the ICU stay (under 1.2 g/kg for more than 50% of the patients) and introduction of ICU diary (25%), was infrequent. Implementation rates of elements A and D were higher in ICUs with specific protocols and fewer ICU beds exclusively for patients with coronavirus disease 2019 infection. Element E was implemented at a higher rate in ICUs that had more ICU beds assigned for them. Conclusions:. This point prevalence study showed low implementation of the ABCDEF bundle. Specific protocols and the number of ICU beds reserved for patients with coronavirus disease 2019 infection might be key factors for delivering appropriate supportive care.

Summary: Despite common consensus about the importance of planar cell polarity (PCP) proteins in tissue orientation, little is known about the mechanisms used by PCP proteins to promote planar polarization of cytoskeletons within individual cells. One PCP protein Fzd6 asymmetrically localizes to the apical cell membrane of multi-ciliated ependymal cells lining the lateral ventricular (LV) wall on the side that contacts cerebrospinal fluid flow. Individual ependymal cells have planar polarized microtubules that connect ciliary basal bodies (BBs) with the cell cortex of the Fzd side to coordinate cilia orientation. Here, we report that cytoplasmic dynein is anchored to the cell cortex of the Fzd side via an adapter protein Daple that regulates microtubule dynamics. Asymmetric localization of cortical dynein generates a pulling force on dynamic microtubules connected to BBs, which in turn orients BBs toward the Fzd side. This is required for coordinated cilia orientation on the LV wall.

Background: A recent meta-analysis compared the relative risks of colorectal cancer between the highest and lowest levels of coffee consumption in the Japanese population. However, this analysis did not define the risks with respect to specific exposure values when considering levels of coffee consumption per day in the study population. Methods: We conducted a two-stage random-effects dose-response meta-analysis of the association between coffee consumption and colorectal cancer among the Japanese. This was performed by modeling coffee consumption using restricted cubic splines to be able to examine a potential nonlinear relation. Results: We identified a total of 26 studies from seven articles, which were distributed separately according to sex and colon/rectum cancers. Data from 14 cohort studies showed that the pooled relative risks for colorectal cancers were less than 1.0 in cases with coffee consumption of 1–3 cups/day and 1.0 in cases with consumption of 4 cups/day or more, although these results were not statistically significant. Data from 12 case-control studies showed that the pooled odds ratios for cancer risk were significantly less than 1.0 in cases with coffee consumption of 1–6 cups/day. Conclusions: Findings from this meta-analysis indicate that moderate coffee consumption may not be associated or may be weakly inversely associated with the risk of colorectal cancer in the Japanese population.

Abstract Background The aim of this study is to investigate the association between treatment in a closed ICU and survival at discharge in patients with sepsis. Methods This is a post hoc analysis utilizing data from the Japan Septic Disseminated Intravascular Coagulation study, including data from patients with sepsis from 2011 to 2013. Multiple logistic regression analysis was used to estimate the association between ICU policy and survival at discharge, and propensity score matching analysis was performed including the same covariates as a sensitivity analysis. Multiple linear regression analysis for the length of ICU stay in surviving patients was also performed with adjustments for the same covariates. Results Two thousand four hundred ninety-five patients were analyzed. The median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 22 [17–29], the median Sequential Organ Failure Assessment (SOFA) score was 9 [7–12], and the overall mortality was 33%. There were 979 patients treated in 17 open ICUs and 1516 patients in 18 closed ICUs. In comparison, the APACHE II score and SOFA scores were significantly higher in patients in closed ICUs (closed vs open = 23 [18–29] vs 21 [16–28]; p