Is Drosophila Dpp/BMP morphogen spreading required for wing patterning and growth?

Secreted signaling molecules act as morphogens to control patterning and growth in many developing tissues. Since locally produced morphogens spread to form a concentration gradient in the surrounding tissue, spreading is generally thought to be the key step in the non-autonomous actions. Here, we review recent advances in tool development to investigate morphogen function using the role of decapentaplegic (Dpp)/bone morphogenetic protein (BMP)-type ligand in the Drosophila wing disc as an example. By applying protein binder tools to distinguish between the roles of Dpp spreading and local Dpp signaling, we found that Dpp signaling in the source cells is important for wing patterning and growth but Dpp spreading from this source cells is not as strictly required as previously thought. Given recent studies showing unexpected requirements of long-range action of different morphogens, manipulating endogenous morphogen gradients by synthetic protein binder tools could shed more light on how morphogens act in developing tissues.

Protein manipulation using single copies of short peptide tags in cultured cells and in Drosophila melanogaster.

Cellular development and function rely on highly dynamic molecular interactions among proteins distributed in all cell compartments. Analysis of these interactions has been one of the main topics in cellular and developmental research, and has been mostly achieved by the manipulation of proteins of interest (POIs) at the genetic level. Although genetic strategies have significantly contributed to our current understanding, targeting specific interactions of POIs in a time- and space-controlled manner or analysing the role of POIs in dynamic cellular processes, such as cell migration or cell division, would benefit from more-direct approaches. The recent development of specific protein binders, which can be expressed and function intracellularly, along with advancement in synthetic biology, have contributed to the creation of a new toolbox for direct protein manipulations. Here, we have selected a number of short-tag epitopes for which protein binders from different scaffolds have been generated and showed that single copies of these tags allowed efficient POI binding and manipulation in living cells. Using Drosophila, we also find that single short tags can be used for POI manipulation in vivo.

Short-term effectiveness and safety of rituximab versus cyclophosphamide for life-threatening ANCA-associated vasculitis: a propensity score analysis of the real-world nationwide database.

OBJECTIVES: Life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with rapidly progressive glomerulonephritis (RPGN) and/or alveolar haemorrhage (AH) has a poor prognosis. Rituximab (RTX) is as effective as cyclophosphamide (CY) in remission induction therapy; however, the effectiveness and safety of RTX have not been established in life-threatening AAV. This study aimed to investigate the short-term effectiveness and safety of RTX in life-threatening AAV with RPGN and/or AH. METHODS: Between April 2018 and March 2020, cases treated with systemic glucocorticoids and RTX or intravenous CY (IVCY) was extracted from a Japanese nationwide inpatient database. Effectiveness was evaluated by in-hospital mortality and severe renal dysfunction requiring haemodialysis (HD) at discharge. Safety was evaluated by the in-hospital incidence of infections. The propensity score (PS) for RTX was estimated. Multivariable Cox and logistic regression with adjustment for PS were conducted to estimate the association of RTX with outcomes. RESULTS: From 16 001 612 hospitalised records, 687 life-threatening AAV cases were extracted. No significant difference in in-hospital mortality (adjusted HR 1.06; 95% CI 0.62 to 1.80) was found between the groups. Although the RTX group had a lower risk of fungal infections (adjusted OR (aOR) 0.45; 95% CI 0.23 to 0.84) and pneumocystis pneumonia (aOR 0.58; 95% CI 0.32 to 1.00), they might have an increased risk of severe renal dysfunction requiring HD at discharge (aOR 2.58; 95% CI 1.02 to 6.91). CONCLUSIONS: In life-threatening AAV, RTX has similar short-term effectiveness on mortality to IVCY. Although RTX might have a lower risk of fungal infections and pneumocystis pneumonia, the short-term renal prognosis might be inferior to IVCY.

Epidemiologic evaluation of pulmonary paragonimiasis in Japan using a Japanese nationwide administrative database.

BACKGROUND: Paragonimiasis is a parasitic disease primarily contracted through consumption of undercooked freshwater crustaceans or wild boar meat. Large-scale nationwide epidemiological data on paragonimiasis are lacking. In this study, we aimed to investigate the nationwide epidemiology of hospitalized patients with paragonimiasis in Japan using a comprehensive nationwide Japanese administrative database. METHODS: We evaluated the Japanese Diagnosis Procedure Combination (DPC) data of patients diagnosed with pulmonary paragonimiasis between April 1, 2012 and March 30, 2020. The patients' address and information, including age, sex, treatment (medication: praziquantel; surgery: open thoracotomy or intracranial mass extirpation), Japan coma scale, comorbidities, and length of hospital stay, were extracted. RESULTS: Of the 49.6 million hospitalized patients, data were extracted on 73 patients with paragonimiasis, of whom 36 were male and 37 were female. The mean age was 49.7 years and the mean length of stay was 12.5 days. The most frequent comorbidity was pleural effusion (31.5 %), followed by pneumothorax (13.7 %). The sites of ectopic paragonimiasis in organs other than the lung included the liver (5.5 %), skin (4.1 %), and brain (2.7 %). Geographically, most patients were from the Kyushu region (54.8 %), followed by the Kanto region (22.0 %). Fukuoka Prefecture had the highest number of patients (22.0 %) by prefecture. During the study period, an average of 9.1 patients/year were hospitalized with lung paragonimiasis in Japan. CONCLUSION: Paragonimiasis has not completely disappeared in Japan; thus, physicians should be aware of paragonimiasis in the Kyushu region, especially in the Fukuoka Prefecture.

Impact of fee-revision policy for gastrostomy on its implementation among older adults with dementia in Japan.

OBJECTIVES: This study aimed to evaluate the impact of the policy to reduce the reimbursement fee for percutaneous endoscopic gastrostomy (PEG) on the number of PEG procedures performed among older adults with dementia. STUDY DESIGN: Interrupted time series (ITS). METHODS: We used the monthly aggregated data of the number of PEG procedures in older adults with dementia (both broad and narrow definitions), between 2012 and 2018, from the claims data in Fukuoka Prefecture, Japan. A single ITS design was used to estimate changes in the outcome following each intervention (i.e., first, second, and third interventions performed in 2014, 2015, and 2016, respectively). A controlled ITS design was applied to estimate the effects after the sequence of interventions (pre-intervention: 2012-2014; post-intervention: 2016-2018). The control group comprised patients with malignant head and neck tumors who underwent PEG procedures outside the scope of this policy restriction. RESULTS: The number of PEG procedures decreased significantly only in the month wherein the third intervention was introduced (broad definition: IRR = 0.11, CI = 0.03-0.49; narrow definition: IRR = 0.15, CI = 0.03-0.75). No significant difference was observed between the treatment and control groups during the post-intervention phase. CONCLUSIONS: The impact of fee-revision policy for PEG on the decrease in PEG procedures among older adults with dementia is remarkably minimal. It is difficult to reduce unnecessary PEG procedures by relying on this financial incentive alone. Policy decision-makers should consider methods to prevent inappropriate use of artificial nutrition for older adults at their end-of-life stage by reforming the health delivery system.

Estimation of the Number of Patients With Mitochondrial Diseases: A Descriptive Study Using a Nationwide Database in Japan.

BACKGROUND: To provide a better healthcare system for patients with mitochondrial diseases, it is important to understand the basic epidemiology of these conditions, including the number of patients affected. However, little information about them has appeared in Japan to date. METHODS: To gather data of patients with mitochondrial diseases, we estimated the number of patients with mitochondrial diseases from April 2018 through March 2019 using a national Japanese health care claims database, the National Database (NDB). Further, we calculated the prevalence of patients, and sex ratio, age class, and geographical distribution. RESULTS: From April 2018 through March 2019, the number of patients with mitochondrial diseases was 3,629, and the prevalence was 2.9 (95% confidence interval [CI], 2.8-3.0) per 100,000 general population. The ratio of females and males was 53 to 47, and the most frequent age class was 40-49 years old. Tokyo had the greatest number of patients with mitochondrial diseases, at 477, whereas Yamanashi had the fewest, at 13. Kagoshima had the highest prevalence of patients with mitochondrial diseases, 8.4 (95% CI, 7.1-10.0) per 100,000 population, whereas Yamanashi had the lowest, 1.6 (95% CI, 0.8-2.7). CONCLUSION: The number of patients with mitochondrial diseases estimated by this study, 3,269, was more than double that indicated by the Japanese government. This result may imply that about half of all patients are overlooked for reasons such as low severity of illness, suggesting that the Japanese healthcare system needs to provide additional support for these patients.

The Effects of Hospital Volume on Short-Term Outcomes of Laparoscopic Surgery for Rectal Cancer: A Large-Scale Analysis of 37,821 Cases on a Nationwide Administrative Database.

INTRODUCTION: Laparoscopic low anterior resection (L-LAR) has become widely accepted for the treatment of rectal cancer. However, little is known about the superiority of L-LAR in a real-world setting (including low-volume hospitals) and the association between the short-term outcomes and hospital volume focusing on L-LAR. METHODS: This is a retrospective cohort study. A total of 37,821 patients who underwent LAR for rectal cancer were analyzed using the Diagnosis Procedure Combination (DPC) database from January 2014 to December 2017. The short-term surgical outcomes were analyzed using a multilevel analysis. Hospital volumes were divided into quartiles, including low (1-31), middle (32-55), high (56-91), and very-high volume (92-444 resections per 4 years). The effects of hospital volume on the outcomes were investigated. RESULTS: The study population included 8,335 patients (22%) who underwent open low anterior resection (O-LAR) and 29,486 patients (78%) who underwent L-LAR. The in-hospital mortality and morbidity were consistent with previous reports. In patients who underwent L-LAR, the in-hospital mortality (0.12% vs. 0.41%; OR: 0.33; p = 0.005), the rate of reoperation (3.76% vs. 6.48%; OR: 0.67; p < 0.001), and the perioperative transfusion rate (3.81% vs. 5.90%; OR: 0.66; p < 0.001) were significantly lower in very-high-volume hospitals than in low-volume hospitals. These effects of hospital volume were not observed in O-LAR. CONCLUSIONS: Our present study demonstrates that high volume improves outcomes in patients who underwent L-LAR in a real-world setting.

Association between COVID-19 infection rates by region and implementation of non-pharmaceutical interventions: a cross-sectional study in Japan.

BACKGROUND: During a pandemic, non-pharmaceutical interventions (NPIs) play an important role in protecting oneself and others from infection. There are large regional differences in COVID-19 infection rates in Japan. We hypothesized that the local infection incidence may affect adherence to individual NPIs. METHODS: This cross-sectional study was conducted online among full-time workers in Japan in December 2020. The questionnaire asked the respondents to identify their habits regarding seven common NPIs (wearing masks, washing hands after the bathroom, disinfecting hands when entering indoors, gargling when returning home, ventilating the room, disinfecting or washing hands after touching frequently touched surfaces, carrying alcohol sanitizers when outdoors). RESULTS: A total of 27 036 participants were analyzed. Compared with the region with the lowest infection rate, five of the seven NPIs showed statistically significant trends across regional infection levels, the two exceptions being wearing masks and washing hands after the bathroom. Multivariate adjustment did not change these trends. CONCLUSIONS: This study found that NPIs were more prevalent in regions with higher incidence rates of COVID-19 in Japanese workers. The findings suggest that the implementation of NPIs was influenced not only by personal attributes but also by contextual effects of the local infection level.

Facility staffing associated with potentially avoidable hospitalizations in nursing home residents in Japan: a retrospective cohort study.

BACKGROUND: Wide variations in facility staffing may lead to differences in care, and consequently, adverse outcomes such as hospitalizations. However, few studies focused on types of occupations. Therefore, we aimed to examine the association between a wide variety of facility staffing and potentially avoidable hospitalizations of nursing home residents in Japan. METHODS: In this retrospective cohort study using long-term care and medical insurance claims data in Ibaraki Prefecture from April 2018 to March 2019, we identified individuals aged 65 years and above who were newly admitted to nursing homes. In addition, facility characteristic data were obtained from the long-term care insurance service disclosure system. Subsequently, we conducted a multivariable Cox regression analysis and evaluated the association between facility staffing and potentially avoidable hospitalizations. RESULTS: A total of 2909 residents from 235 nursing homes were included. The cumulative incidence of potentially avoidable hospitalizations at 180 days was 14.2% (95% confidence interval [CI] 12.7-15.8). Facilities with full-time physicians (adjusted hazard ratio [HR]: 0.59, 95% CI: 0.37-0.94) and a higher number of dietitians (HR: 0.72, 95% CI: 0.54-0.97) were significantly associated with a lower likelihood of potentially avoidable hospitalizations. In contrast, having nurses or trained caregivers during the night shift (HR: 1.72, 95% CI: 1.25-2.36) and a higher number of care managers (HR: 1.37, 95% CI: 1.03-1.83) were significantly associated with a high probability of potentially avoidable hospitalizations. CONCLUSIONS: We revealed that variations in facility staffing were associated with potentially avoidable hospitalizations. The results suggest that optimal allocation of human resources, such as dietitians and physicians, may be essential to reduce potentially avoidable hospitalizations. To provide appropriate care to nursing home residents, it is necessary to establish a system to effectively allocate limited resources. Further research is warranted on the causal relationship between staff allocation and unnecessary hospitalizations, considering the confounding factors.

The Current Status of Suicide and Medical Care System in Japan: An Analysis of 81,407 Patients Using the Diagnosis Procedure Combination Database.

Japan has a high suicide mortality rate compared to other developed countries. To reduce suicide mortality in Japan, it is important to systematically analyze factors related to death of patients with suicide attempt. This study aimed to analyze the characteristics of patients with suicide attempt, and the factors related to their death using the Diagnosis Procedure Combination (DPC) data- a nationally representative inpatient database. We collected 81,407 cases of suicide attempt from 2016 to 2018 from DPC data and performed a multilevel logistic analysis of factors associated with death discharges. The analysis results showed that patients who received psychiatric liaison care had a lower mortality rate, but only 0.6% of surviving patients received psychiatric liaison care after admission. The odds ratio (OR) of death was high for hanging (28.86; p < 0.001) and jumping (16.28; p < 0.001), compared to wrist cutting. Patients without a psychiatric diagnosis were more likely to choose means such as hanging (14.1%) than those with a psychiatric disorder. The weekend cases had a higher OR of death than weekday (Wednesday as reference) cases (Friday 1.14, p = 0.011; Saturday 1.60, p < 0.001; Sunday 1.67, p < 0.001). Based on these findings, we suggest that improving the availability and quality of psychiatric care in acute care hospitals and primary care settings, as well as enhancing the emergency department system on weekends, could help reduce the mortality of suicide attempts.

Analysis of the risk factors of mortality in elderly patients with hip fracture using a combined database of medical and long-term care insurance claims data.

BACKGROUND: The present study evaluated the risk of mortality in elderly hip fracture, focusing on comorbidities and nursing care levels. METHODS: The present study was an observational cohort study that used a combined database of medical and long-term care insurance (LTCI) claims data from one prefecture in Japan between 2011 and 2016. In total, 6125 patients aged 65 years and older were selected from acute care hospitals with a diagnosis of "hip fracture" between March 2011 and March 2012. The impact of long-term care insurance claim evaluation levels and comorbidities at recruitment time was investigated using this dataset. These patients were followed up monthly until March 2016. Based on this person-month dataset, survival analysis was performed with death as the endpoint. Cases in which receipt data were missing during the middle of the observation period and cases in which the patient survived at the end of the observation period were censored. RESULTS: The number of deaths during the observation period was 635 (10.4%). The impact of comorbidities and nursing care level on mortality were both significant as follows: high nursing care level before the fracture (hazard ratio: 1.09, P < 0.001), comorbidities of malignant diseases (HR: 1.45, P < 0.001), heart disease (hazard ratio: 1.20, P = 0.037), pneumonia (hazard ratio: 1.27, P < 0.001), chronic obstructive pulmonary disease (hazard ratio: 1.28, P = 0.026), renal failure (hazard ratio: 1.44, P < 0.001), and dementia (hazard ratio: 1.27, P = 0.013). CONCLUSION: The results of this study showed that a high level of nursing care and presence of comorbidities such as malignant diseases, heart diseases, pneumonia, chronic obstructive pulmonary disease, renal failure, and dementia increased mortality in elderly patients with hip fracture. Furthermore, this study showed the usefulness of a combined database of medical and LTCI claims data for clinical and health service-related research in the field of orthopedics.

Association of Preoperative Rehabilitation With Postoperative Length of Hospital Stay for Elderly Lung Cancer Patients.

This study aimed to evaluate the effect of preoperative rehabilitation on postoperative hospital stay in elderly lung cancer patients following lung resection. This was a retrospective observational study using the Japanese Diagnosis Procedure Combination database. Data of patients diagnosed between April 2016 and March 2020 were collected. Patients were identified using the International Statistical Classification of Disease and Related Health Problems Version 10-10 codes, C34.0-C34.3 and C34.8. Multilevel linear regression analysis was performed to evaluate the effect of preoperative rehabilitation on the length of hospital stay. A total of 9,393 patients were included in the study. Univariate analysis showed that preoperative rehabilitation was significantly associated with postoperative length of hospital stay (coefficient: -1.61; 95% confidence interval: -2.42, -0.81; P <0.001). In addition, multivariate analysis showed preoperative rehabilitation to be associated with a significant decrease in postoperative length of hospital stay (coefficient=-1.38; 95% confidence interval: -2.19, -0.58; P =0.001). Preoperative rehabilitation may shorten length of hospital stay in elderly patients with lung cancer.

The Relationship Between Preoperative Frailty Risk as Assessed by the Hospital Frailty Risk Score and the Outcome at Discharge in Coronary Artery Bypass Grafting (CABG) Patients: A Retrospective Observational Study Using the Diagnosis Procedure Combination Database.

The relationship between the Hospital Frailty Risk Score (HFRS)-based frailty risk and outcomes after coronary artery bypass grafting (CABG) is yet unclear. The objective of this study was to investigate the relationship between preoperative frailty risk as assessed by the HFRS and postoperative outcomes in patients undergoing CABG. This observational study used the diagnosis procedure combination (DPC) system in Japan (2014-2017). In total, 35,015 adults aged ≥ 65 years and diagnosed with angina pectoris and acute myocardial infarction who had undergone CABG were enrolled. We investigated the association between the HFRS-based frailty risk and the home discharge rate, as well as the prevalence of complications. Multilevel logistic regression analysis revealed that having an HFRS ≥ 5 was a determinant of lower home discharge rate (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.49-0.74, P <0.01), aspiration pneumonia (OR 2.25, 95%CI 1.27-3.96, P <0.01) and disuse syndrome (OR 1.90, 95%CI 1.23-2.94, P <0.01). Preoperative stratification of frailty risk using HFRS may help in predicting postoperative progress and in planning postoperative rehabilitation.

The S. pombe CDK5 ortholog Pef1 regulates sexual differentiation through control of the TORC1 pathway and autophagy.

In Schizosaccharomyces pombe, a general strategy for survival in response to environmental changes is sexual differentiation, which is triggered by TORC1 inactivation. However, mechanisms of TORC1 regulation in fission yeast remain poorly understood. In this study, we found that Pef1, which is an ortholog of mammalian CDK5, regulates the initiation of sexual differentiation through positive regulation of TORC1 activity. Conversely, deletion of pef1 leads to activation of autophagy and subsequent excessive TORC1 reactivation during the early phases of the nitrogen starvation response. This excessive TORC1 reactivation results in the silencing of the Ste11-Mei2 pathway and mating defects. Additionally, we found that pef1 genetically interacts with tsc1 and tsc2 for TORC1 regulation, and physically interacts with three cyclins, Clg1, Pas1 and Psl1. The double deletion of clg1 and pas1 promotes activation of autophagy and TORC1 during nitrogen starvation, similar to what is seen in pef1Δ cells. Overall, our work suggests that Pef1-Clg1 and Pef1-Pas1 complexes regulate initiation of sexual differentiation through control of the TSC-TORC1 pathway and autophagy.

Toward Engineered Biosynthesis of Drugs in Human Cells.

Biosynthetic genes are not only responsible for the formation of bioactive substances but also suited for other applications including gene therapy. To test the feasibility of human cells producing antibiotics in situ when provided with a heterologous biosynthetic gene, we focused on cytochrome P450, the class of enzymes important in conferring bioactivity to natural product precursors. We selected Fma-P450 that plays a central role in the fumagillin antimicrobial biosynthesis in Aspergillus fumigatus to examine fungal metabolite production by HeLa cells that express fma-P450 heterologously. Here we show that HeLa cells harboring fma-P450 can biosynthesize 5-hydroxyl-ß-trans-bergamoten and cytotoxic 5-epi-demethoxyfumagillol when supplemented with the nontoxic precursor ß-trans-bergamotene. While the production level was insufficient to effect cell death, we demonstrate that programming human cells to autogenerate antibiotics by introducing a heterologous biosynthetic gene is feasible.

Epidemiological Study of Hospital Admissions for Food-Induced Anaphylaxis Using the Japanese Diagnosis Procedure Combination Database.

BACKGROUND: Food allergies are common among children, and food-induced anaphylaxis (FIA) is a serious disease with a risk of death; however, there is yet to be a large-scale epidemiological study on causative foods in Japan. The purpose of this study was to identify foods that cause FIA in Japan. METHODS: We identified 9,079 patients from the Japanese Diagnosis Procedure Combination Database who were admitted for treatment for FIA from April 1, 2014 through March 31, 2017. We extracted data on patient sex, age, use of epinephrine injections on the first day, prescription for epinephrine self-injection on the day of discharge, length of stay, readmission, and causative foods. RESULTS: The most common causative food was eggs, followed by wheat, milk, peanuts, and buckwheat. The most common causative food in each age group was eggs among 0-3-year-olds, milk among 4-6-year-olds, peanuts among 7-19-year-olds, and wheat among those aged 20 years and older. Epinephrine was used at admission among about 40%, 50%, and over 60% of cases in which the causative food was eggs; wheat, milk and peanuts; and buckwheat, respectively. The proportion of cases with a prescription for epinephrine self-injection at discharge was highest among those in which the causative food was wheat, followed by peanuts, buckwheat, milk, and eggs. CONCLUSIONS: FIA due to peanuts has become as common in Japan as it is in the West. These results suggest the importance of taking measures to prevent peanut allergies because children cannot make adequate decisions regarding food.

Mortality changes for patients with pneumococcal pneumonia from 2012 to 2017 in Japan.

INTRODUCTION: Pneumococcal pneumonia has a high morbidity and mortality in adults, especially those ≥65 years old. In the past decade, pneumococcal vaccination programs have been initiated worldwide, however, few data concerning mortality changes are available in pneumococcal pneumonia patients and there are no reports clarifying these current changes in Japan. METHODS: Japanese patients ≥65 years old hospitalized with pneumococcal pneumonia between April 2012 and March 2018 were analyzed using the Diagnostic Procedure Combination database. In-hospital mortality was evaluated, and the odds ratios for this outcome in each fiscal year compared with that in 2012 was analyzed using multivariable logistic regression models. RESULTS: Between 2012 and 2017, data of 47,375 pneumococcal pneumonia patients ≥65 years old were extracted. The incidence per 1000 person-years for in-hospital mortality was 60.4 in 2012, 56.8 in 2013, 63.2 in 2014, 56.1 in 2015, 73.0 in 2016, and 67.4 in 2017 and the odds ratios for in-hospital mortality in 2013, 2014, 2015, 2016, and 2017 compared with that in 2012 were 1.00, 1.05, 1.04, 1.06, and 0.98, respectively. There were no significant differences between 2012 and each year from 2013 to 2017. Low BMI; low ADL score; high A-DROP score; comorbid malignancy and heart failure; the coexistence of invasive pneumococcal infection; and the use of invasive mechanical ventilation were independent risk factors for in-hospital mortality. CONCLUSIONS: There were no changes in in-hospital mortality in pneumococcal pneumonia patients between 2012 or each year from 2013 to 2017 and further epidemiological observations are necessary.

Effects of additive corticosteroid therapy on 90-day survival in patients with community-onset pneumonia.

INTRODUCTION: Systemic corticosteroid therapy is occasionally used as an additive therapy, especially for patients with severe pneumonia. However, its recommendation for use in patients with pneumonia varies worldwide, and its efficacy is unclear. METHODS: Adult Japanese patients hospitalized with community-onset pneumonia between January and December 2012 were analyzed using the Diagnostic Procedure Combination database. The patients were classified into mild-to-moderate and severe groups using the A-DROP (age, dehydration, respiration, orientation, and blood pressure) system. The 90-day survival rate was evaluated between the presence or absence of corticosteroid treatment using the Kaplan-Meier method in the overall, mild-to-moderate and severe groups, respectively. The patients' clinical characteristics were adjusted between the two groups using the inverse probability of treatment weighting method. RESULTS: Among 123,811, 110,534 patients were classified as mild-to-moderate grade (corticosteroid group: 8,465, non-corticosteroid group: 102,069) and 13,277 patients were classified as severe grade (corticosteroid group: 1,338, non-corticosteroid group: 11,939). The 90-day survival rate was higher in the non-corticosteroid group than in the corticosteroid group in patients with pneumonia of overall grade (weighted hazard ratio [HR]: 1.36; P < 0.001) and those with mild-to-moderate grade (weighted HR: 1.46; P < 0.001). However, there were no significant differences in the outcomes between the two groups in those with severe grade (weighted HR: 1.08; P = 0.38). CONCLUSIONS: Additive systemic corticosteroid therapy may be related to poor 90-day prognosis in patients with mild-to-moderate grade community-onset pneumonia, although it may not be positively associated with its prognosis in those with severe grade.

Effect of COVID-19 infection related experiences on social behaviors when a state of emergency is declared: a cohort study.

BACKGROUND: Restricting the movement of the public to gathering places and limiting close physical contact are effective measures against COVID-19 infection. In Japan, states of emergency have been declared in specific prefectures to reduce public movement and control COVID-19 transmission. We investigated how COVID-19 infection related experiences including people with a history of infection, people with a history of close contact, and people whose acquaintances have been infected, affected self-restraint from social behaviors during the second state of emergency in Japan. METHODS: A prospective cohort study was conducted among workers aged 20-65 years using data from an internet survey. The baseline survey was conducted on December 22-25, 2020, and a follow-up survey was on February 18-19, 2021. There were 19,051 participants who completed both surveys and were included in the final analysis. We identified eight social behaviors: (1) eating out (4 people or fewer); (2) eating out (5 people or more); (3) gathering with friends and colleagues; (4) day trip; (5) overnight trip (excluding visiting home); (6) visiting home; (7) shopping for daily necessities; and (8) shopping for other than daily necessities. We set self-restraint regarding each social behavior after the second state of emergency was declared in January 2021 as the dependent variable, and COVID-19 infection related experiences as independent variables. Odds ratios were estimated using multilevel logistic regression analyses nested in the prefecture of residence. RESULTS: Significant differences by COVID-19 infection related experiences were identified: compared to people without COVID-19 related experiences, people with a history of COVID-19 were less likely self-restraint from most social behaviors. People whose acquaintance had been diagnosed with COVID-19 were significantly more likely to refrain from most social behaviors. There was no significant difference in any social behaviors for people with a history of close contact only. CONCLUSION: To maximize the effect of a state of emergency, health authorities should disseminate information for each person in the target population, taking into account potential differences related to the infection related experiences.

Association between willingness to receive the COVID-19 vaccine and sources of health information among Japanese workers: a cohort study.

BACKGROUND: It is important to achieve herd immunity by vaccinating as many people as possible to end the COVID-19 pandemic. We investigated the relationship between willingness to receive vaccination and sources of health information among those who did not want to be vaccinated against COVID-19. METHODS: This prospective cohort study collected data using a self-administered questionnaire survey. The baseline survey was conducted during December 22-25, 2020, and the follow-up survey during February 18-19, 2021. Participants were aged 20-65 years and worked at the time of the baseline survey (N = 33,087). After excluding 6,051 invalid responses, we included responses from 27,036 participants at baseline. In total, 19,941 people responded to the follow-up survey (74% follow-up rate). We excluded 7,415 participants who answered "yes" to the question "If a COVID-19 vaccine becomes available, would you like to get it?" in the baseline survey. We finally analyzed 12,526 participants. RESULTS: The odds ratio for change in willingness to be vaccinated from "no" to "yes" differed by source of health information. Compared with workers that used TV as a source of information, significantly fewer people who reported getting information from the Internet and friends/colleagues were willing to get the vaccine. CONCLUSIONS: It is important to approach workers who do not watch TV when implementing workplace vaccination programs. It is likely that willingness to be vaccinated can be increased through an active company policy whereby the top management recommend vaccination, coupled with an individual approach by occupational health professionals. TRIAL REGISTRATION: Not applicable.