Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence.

The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre- and post-surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non-cirrhotic or single-tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long-term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4-week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p = .022). In conclusion, serum MYCN holds promise for biomarker-based precision medicine for the prevention of HCC, long-term prognosis of early-stage HCC, and identification of high-response subgroups for ACR-based treatment.

Correction: Impact of the COVID-19 pandemic on exercise habits and overweight status in Japan: a nation-wide panel survey.

[This corrects the article DOI: 10.1371/journal.pgph.0001732.].

Impact of the COVID-19 pandemic on exercise habits and overweight status in Japan: A nation-wide panel survey.

A catastrophic disaster may cause distant health impacts like immobility and obesity. The aim of this research was to analyse the association of the COVID-19 pandemic and lifestyle factors -exercise habit and overweight status in the Japanese population. Nation-wide online questionnaires were conducted five times from October 2020 to October 2021. The changes in exercise habit, body mass index (BMI) and overweight status (BMI >25kg/m2) were compared between the first questionnaire and a questionnaire conducted a year later. Risk factors for losing exercise habit or becoming overweight were analysed using multiple regression. Data were obtained from 16,642 participants. In the early phase of the pandemic, people with high income and elderly females showed a higher risk for decreased exercise days. The proportion of overweight status increased from 22.2% to 26.6% in males and from 9.3% to 10.8% in females. Middle-aged males, elderly females, and males who experienced SARS-CoV-2 infection were at higher risk of becoming overweight. Our findings suggest that risks for immobility and overweight are homogeneous. Continuous intervention for elderly females and long-term intervention for males infected with SARS-CoV-2 might be especially needed. As most disasters can cause similar social transformation, research and evaluation of immobility and obesity should address future disaster preparation/mitigation plans.

Determination of a Serum 25-Hydroxyvitamin D Reference Ranges in Japanese Adults Using Fully Automated Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Despite an increasing interest in vitamin D status, a reference range of the nutrient has not been fully established. This is partly due to a paucity of standardized measuring systems with high throughput. In addition, the range may vary by populations and may change with modernization of lifestyles. OBJECTIVES: This study aims to calculate the current reference concentration of 25-hydroxyvitamin D (25(OH)D) among healthy people living in an urban area in Japan. METHODS: A newly developed fully automated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) system was used to measure serum 25(OH)D concentrations. Reproducibility was assessed by measuring standardized samples. Accuracy was validated by comparing with commercially available immunoassays. Then, mass screening was conducted targeting participants who received medical checkups in Tokyo from April 2019 to March 2020, and the reference ranges were calculated. RESULTS: The coefficients of variations of interoperator and interday reproducibility were 4.1%-8.5% and 3.7%-8.0% for 25-hydroxyvitamin D2 (25(OH)D2) and 4.7%-7.0% and 4.0%-6.9% for 25-hydroxyvitamine D3, respectively. The measured total 25(OH)D concentrations correlated well with those measured by immunoassays. In total, 5518 participants were measured for 25(OH)D concentrations, among whom 98% showed inadequate concentrations (<30 ng/mL). The reference ranges of total 25(OH)D for female, male, and total participants were 7-30 ng/mL, 5-27 ng/mL, and 6-29 ng/mL, respectively. After excluding those with abnormal renal and liver function, the range was 6-30 ng/mL. CONCLUSIONS: The high prevalence of vitamin D insufficiency among seemingly healthy population may be attributed to lifestyle characteristics of people living in urban areas of Japan, including spending less time outdoors and lower intake of traditional foods. Longitudinal follow-up and mass screenings targeting different population will help elucidate reasons for discrepancies between official guidelines and the observed concentrations, to which the well-validated measurement system is essential.

Preferable outcome of Janus kinase inhibitors for a group of difficult-to-treat rheumatoid arthritis patients: from the FIRST Registry.

BACKGROUNDS: Treatment of difficult-to-treat rheumatoid arthritis (D2T RA) is one of the greatest unmet needs in rheumatology. This study aims to find out preferable treatment options for a group of D2T RA patients who are refractory to multiple biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). METHODS: Data were obtained from patients enrolled in the FIRST Registry who started either TNF inhibitor (TNFi), interleukin-6 receptor inhibitor, cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin, or Janus-kinase inhibitor (JAKi) in the period of August 2013 to December 2020. Those who failed to ≥ 2 and ≥ 3 b/tsDMARDs were categorised as D2T RA and very D2T RA (vD2T RA), respectively. Change in Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire Disability Index were compared among the groups using propensity-based inverse probability treatment weighted (IPTW) method. RESULTS: Of 2128 cases included, 353 were categorised as D2T RA. Among the D2T RA, 106 were identified as vD2T RA. JAKi showed a significant improvement in CDAI in the patients with D2T RA and vD2T RA, compared to IPTW-adjusted patients treated with the other 3 regimens. Latent class analysis of the trajectories of treatment response revealed that the proportion of a group of patients who showed poor response was lower among the JAKi subgroup than among those with other subgroups. This superiority of JAKi was more apparent among methotrexate- and glucocorticoid-free individuals. The hazard ratio of severe adverse events was comparable among the four treatment subgroups in both the D2T RA and b/tsDMARD-naïve groups. CONCLUSIONS: This study compared responsiveness to different classes of b/tsDMARDs among D2T RA and vD2T RA patients who were refractory to multiple b/tsDMARDs. The results suggest JAKi is a preferable treatment choice for this type of D2T RA.

Association between COVID-19 vaccine hesitancy and generalized trust, depression, generalized anxiety, and fear of COVID-19.

BACKGROUND: Although numerous studies have been published on the predictors of COVID-19 vaccine hesitancy, some possible predictors remain underexplored. In this study, we explored the associations of unwillingness and indecisiveness regarding COVID-19 vaccination with generalized trust, mental health conditions such as depression and generalized anxiety, and fear of COVID-19. METHODS: Data of wave 1 (from October 27 till November 6, 2020) and wave 3 (from April 23 till May 6, 2021) of a longitudinal online study conducted in Japan were used for the analyses. Unvaccinated participants were asked at wave 3 about their willingness to be vaccinated, with possible responses of willing, unwilling, or undecided. These three responses were used as the outcome variable, and multinomial logistic regression analyses were conducted with willingness to be vaccinated as the reference group. Explanatory variables included generalized trust, depression, generalized anxiety, and fear of COVID-19 both at wave 1 and 3, and sociodemographic and health-related variables. RESULTS: Of the 11,846 valid respondents, 209 (1.8%) answered that they had already been vaccinated against COVID-19, 7089 (59.8%) responded that they were willing to be vaccinated, 3498 (29.5%) responded that they were undecided, and 1053 (8.9%) responded that they were unwilling to be vaccinated. After adjusting for covariates, we found that: (1) participants with lower levels of generalized trust at wave 1 and 3 were more likely to be undecided or unwilling at wave 3; (2) respondents with moderately severe or severe depression at wave 1 and 3 were more likely to be undecided at wave 3; (3) participants with moderate or severe levels of generalized anxiety at wave 3 but not at wave 1 were more likely to be unwilling at wave 3; and (4) respondents with high levels of fear of COVID-19 at wave 1 and 3 were less likely to be undecided and unwilling at wave 3. CONCLUSIONS: Generalized trust, mental health conditions such as depression and generalized anxiety, and low level of fear of COVID-19 are associated with unwillingness or indecision regarding being vaccinated against COVID-19.

Difficult-to-treat rheumatoid arthritis with respect to responsiveness to biologic/targeted synthetic DMARDs: a retrospective cohort study from the FIRST registry.

OBJECTIVES: Difficult-to-treat rheumatoid arthritis (dt-RA) is an emerging concept defined as persistency of signs and/or symptoms despite prior treatment. However, whether this refractoriness affects effectiveness and tolerance to next treatment is not fully understood. This study aimed to find cut-off values for a definition of dt-RA with respect to responsiveness to newly used biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). METHODS: A retrospective cohort study was conducted using the FIRST registry. An inadequate response to current b/tsDMARDs was defined as clinical disease activity index >10 at week 22 or termination of treatment within 22 weeks due to insufficient efficacy. Cut-off values were defined according to the number of past failures to DMARDs and current dose of glucocorticoid. Responsiveness to newly used b/tsDMARDs were compared with respect to above versus below cut-off values. RESULTS: Failures to ≥2 conventional synthetic DMARDs (csDMARDs) and ≥4 b/tsDMARDs as well as ≥3mg/day of glucocorticoid were independent cut-off values associated with poor responsiveness to newly used b/tsDMARD treatment. Concomitant use of glucocorticoid was significantly correlated with an increased hazard of infection. Failures to ≥2 csDMARDs was associated with less improvement in inflammatory symptoms, while that to ≥4 b/tsDMARDs was associated with less improvement in health assessment questionnaire and global health as well. CONCLUSIONS: We propose cut-off values of ≥2 failures to csDMARDs and/or ≥4 b/tsDMARDs as a definition of dt-RA with respect to responsiveness to use of b/tsDMARDs.

Establishment of a Rapid Detection System for ISG20-Dependent SARS-CoV-2 Subreplicon RNA Degradation Induced by Interferon-α.

Inhaled nebulized interferon (IFN)-α and IFN-ß have been shown to be effective in the management of coronavirus disease 2019 (COVID-19). We aimed to construct a virus-free rapid detection system for high-throughput screening of IFN-like compounds that induce viral RNA degradation and suppress the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We prepared a SARS-CoV-2 subreplicon RNA expression vector which contained the SARS-CoV-2 5'-UTR, the partial sequence of ORF1a, luciferase, nucleocapsid, ORF10, and 3'-UTR under the control of the cytomegalovirus promoter. The expression vector was transfected into Calu-3 cells and treated with IFN-α and the IFNAR2 agonist CDM-3008 (RO8191) for 3 days. SARS-CoV-2 subreplicon RNA degradation was subsequently evaluated based on luciferase levels. IFN-α and CDM-3008 suppressed SARS-CoV-2 subreplicon RNA in a dose-dependent manner, with IC50 values of 193 IU/mL and 2.54 µM, respectively. HeLa cells stably expressing SARS-CoV-2 subreplicon RNA were prepared and treated with the IFN-α and pan-JAK inhibitor Pyridone 6 or siRNA-targeting ISG20. IFN-α activity was canceled with Pyridone 6. The knockdown of ISG20 partially canceled IFN-α activity. Collectively, we constructed a virus-free rapid detection system to measure SARS-CoV-2 RNA suppression. Our data suggest that the SARS-CoV-2 subreplicon RNA was degraded by IFN-α-induced ISG20 exonuclease activity.

Behavioral Factors Associated with COVID-19 Risk: A Cross-Sectional Survey in Japan.

BACKGROUND: Behaviors to avoid infection are key to minimizing casualties of the COVID-19 pandemic, as well as to avoid excessive interventions that are less effective. This study aims to identify behavioral patterns associated with SARS-CoV-2 infection in the real world. METHODS: A questionnaire-based cross-sectional study was conducted targeting a research panel of NTTCom Online Marketing Solutions Corporation or its affiliates. Data were extracted so that their demographic composition ratios matched the population estimates. Individuals who answered with consistency to have been diagnosed with SARS-CoV-2 at a medical facility were categorized into a SARS-CoV-2 group. Differences in lifestyles were compared using multiple regression and inverse probability weighing. RESULTS: In total 13,277 participants were included, of whom 44 (0.33%) were categorized as the SARS-CoV-2 group. Diagnosis of SARS-CoV-2 was negatively correlated with crowd avoidance, mask wearing, and hand-washing behavior. On the contrary, the diagnosis was positively correlated with some behaviors that appear to be preventive actions against the infection, such as changing clothes frequently, sanitizing belongings, and remote working. CONCLUSIONS: It is important to conduct evidence-based intervention on people's behaviors and to avoid excessive interventions that are less effective, so that people can minimize the indirect harm, such as exhaustion and economic loss.

Prevention and Control of COVID-19 in Imperfect Condition: Practical Guidelines for Nursing Homes by Japan Environment and Health Safety Organization (JEHSO).

Infection control at nursing homes is a top priority to address the COVID-19 pandemic because people who are the most vulnerable to the pathogen live in close contact. Currently, control measures specifically for nursing homes often ignore under-resourced condition of the facilities. To make guidelines assuming realistic conditions, an expert meeting with 16 members established the key challenges in nursing homes, the basics of infection control, and the major transmission routes. A list of existing guidance was compiled and each item in the list was peer-reviewed by eight experts considering three aspects: significance, scientific validity, and feasibility. Factors related to the nursing home environment, the nature of SARS-CoV-2 transmission, and patient characteristics were identified as the causes of difficulties in infection control at nursing homes. To develop realistic prevention measures in under-resourced condition such as nursing homes, we may need to accept there are no perfect control measures that can achieve zero risk. Instead, the guidelines are based on the concept of deep defense, and practical checklists with 75 items were established. The evaluation of nursing homes by independent organizations using the checklists would be helpful to achieve sustainable infection control.

'Life communication' after the 2011 Fukushima nuclear disaster: what experts need to learn from residential non-scientific rationality.

After chemical, biological, radiological, nuclear or explosive (CBRNE) disasters, trepidation and infodemics about invisible hazards may cause indirect casualties in the affected society. Effective communication regarding technical issues between disaster experts and the residents is key to averting such secondary impacts. However, misconceptions about scientific issues and mistrust in experts frequently occur even with intensive and sincere communications. This miscommunication is usually attributed to residents' conflicts with illiteracy, emotion, value depositions and ideologies. However, considering that communication is an interactive process, there are likely to be additional factors attributable to experts. This article aims to summarize the gaps in rationality between experts and residents observed after the 2011 Fukushima nuclear disaster to describe how residents perceived experts. There were discrepancies in the perception of 'facts', the perception of probability, the interpretation of risk comparison, what were included as risk trade-offs, the view of the disaster, whose behavior would be changed by the communication and whether risk should be considered a science. These findings suggest that there was a non-scientific rationality among residents, which often exercised a potent influence on everyday decision-making. It might not be residents but experts who need to change their behavior. The discrepancies described in this article are likely to apply to communications following any CBRNE disasters that affect people's lives, such as the current COVID-19 pandemic. Therefore, our experiences in Fukushima may provide clues to averting mutual mistrust between experts and achieving better public health outcomes during and after a crisis.

Similarity of Response to Biologics Between Elderly-onset Rheumatoid Arthritis (EORA) and Non-EORA Elderly Patients: From the FIRST Registry.

OBJECTIVE: Increasing numbers of patients are developing rheumatoid arthritis (RA) at an older age, and optimal treatment of patients with elderly-onset RA (EORA) is attracting greater attention. This study aimed to analyze the efficacy and safety of biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in EORA and non-EORA elderly patients. METHODS: A cohort of patients with RA treated with b/tsDMARDs were retrospectively analyzed. Only patients aged ≥ 60 years were included. Among them, patients who developed RA aged ≥ 60 years were categorized as EORA, whereas those aged < 60 years were categorized as non-EORA elderly. Disease activity was compared between the EORA and non-EORA elderly groups. RESULTS: In total, 1040 patients were categorized as EORA and 710 as non-EORA elderly. There were no significant differences in characteristics at baseline between the 2 groups. The proportion of patients with low and high disease activity was comparable at Weeks 2, 22, and 54 between the EORA and the non-EORA elderly group. There were no significant differences in the reasons for the discontinuation of b/tsDMARDs between the 2 groups. Elderly RA onset did not affect changes in Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index, nor did it affect the reasons for b/tsDMARD discontinuation between the 2 groups. The trajectory analysis on CDAI responses to b/tsDMARDs for 54 weeks identified 3 response patterns. The proportion of patients categorized into each group and CDAI response trajectories to b/tsDMARDs were very similar between EORA and non-EORA elderly patients. CONCLUSION: CDAI response patterns to b/tsDMARDs and HR of adverse events were similar between EORA and non-EORA elderly patients.

Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin.

Astrocytes are major glial cells that play a critical role in brain homeostasis. Abnormalities in astrocytic function, such as hepatic encephalopathy (HE) during acute liver failure, can result in brain death following brain edema and the associated astrocyte swelling. Recently, we have identified alpha 1-antichymotripsin (ACT) to be a biomarker candidate for HE. ACT induces astrocyte swelling by upregulating aquaporin 4 (AQP4); however, the causal connection between these proteins is not clear yet. In this study, we utilized a microarray profile to screen the differentially expressed genes (DEGs) in astrocytes treated with ACT. We then performed Gene Ontology, REACTOME, and the comprehensive resource of mammalian protein complexes (CORUM) enrichment analyses of the identified DEGs. The results of these analyses indicated that the DEGs were enriched in pathways activating adenylate cyclase (AC)-coupled G protein-coupled receptors (GPCRs) and therefore were involved in the cyclic adenosine monophosphate (cAMP) signaling. These results indicate that ACT may act as a ligand of Gs-GPCRs and subsequently upregulate cAMP. As cAMP is known to upregulate AQP4 in astrocytes, these results suggest that ACT may upregulate AQP4 by activating AC GPCRs and therefore serve as a therapeutic target for acute HE.

Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study.

BACKGROUND: With advancement in the treatment options of rheumatoid arthritis (RA), optimising the outcomes of difficult-to-treat patients has become increasingly important in clinical practice. In particular, insensitivity to first-line biologic disease-modifying anti-rheumatic drugs (bDMARD) is becoming a significant problem because it may decrease the treatment adherence of patients. This study aimed to compare RA patients with an insensitivity and those with a poor response to initial treatment with tumour necrosis factor inhibitors (TNFis), which are the most frequently used bDMARDs. METHODS: This is a retrospective cohort study using clinical data from the FIRST registry. bDMARD-naïve RA patients treated with tumour necrosis factor inhibitors (TNFis) from August 2003 to May 2019 were included and categorised into three groups: TNFi insensitivity, poor response to TNFis and controls. TNFi insensitivity was defined as follows: (1) discontinuation of TNFi treatment within 22 weeks due to lack of any response, or (2) an increase in the disease activity score in 28 joints-C-reactive protein (DAS28-CRP) of > 0.6 at week 22 compared with week 0. Among the remaining patients, those with a DAS28-CRP > 2.6 at week 22 were categorised in the poor response group. RESULTS: Of the included patients, 94 were classified in the insensitivity, 604 in the poor response and 915 in the control. A higher DAS28-CRP before treatment was a risk factor for a poor response but not for insensitivity. In contrast, dose escalation of infliximab decreased the risk of a poor response but not that of insensitivity. CONCLUSIONS: In future research, poor and insensitivity to bDMARDs should be assessed separately to fully elucidate the aetiology of, and risk factors for, bDMARD refractoriness.

The fasting 13C-glucose breath test is a more sensitive evaluation method for diagnosing hepatic insulin resistance as a cardiovascular risk factor than HOMA-IR.

BACKGROUND: Although we previously reported the fasting 13C-glucose breath test (FGBT) was useful for the diagnosis of hepatic insulin resistance (IR), there has been no report in an actual clinical setting. We therefore performed the FGBT in patients with heart disease to assess the difference in the diagnostic ability of HIR between the FGBT and HOMA-IR; we also assessed the relationship between the FGBT and known cardiovascular risk factors. METHODS: Two hundred patients (100 with ischemic heart disease [IHD], 50 with non-ischemic heart disease [NIHD], and 50 with non-cardiac lifestyle-related disease [NCD]) participated in this study. The data of 40 healthy volunteers [HV] was obtained in our previous study. We evaluated the 13C excretion rate at 120 min (C120) as the indicator of hepatic IR in the FGBT. RESULTS: The value of C120 in each disease group was significantly lower than in HV, but the HOMA-IR in the IHD and NCD groups was not significantly different from that in HV. The value of C120 significantly correlated with known cardiovascular risk factors. CONCLUSIONS: These results indicated the FGBT is more sensitive than HOMA-IR for evaluating hepatic IR as a cardiovascular risk factor and is likely useful for managing patients to prevent cardiovascular disease.

The Great East Japan Earthquake, Tsunamis, and Fukushima Daiichi Nuclear Power Plant Disaster: Lessons for Evidence Integration from a WADEM 2017 Presentation and Panel Discussion.

In April 2017, some of the health impacts of the 2011 Great East Japan Earthquake, tsunamis, and resultant Fukushima Daiichi nuclear power plant disaster (Okuma, Fukushima Prefecture, Japan) were presented at the 19th Congress of the World Association for Disaster and Emergency Medicine (WADEM; Madison, Wisconsin USA) in Toronto, Canada. A panel discussion was then opened by asking audience members about their experiences in their own countries, and how they would suggest taking steps to reach the goals of the Sendai Framework for Disaster Risk Reduction 2015-2030. This paper summarizes the presentation and panel discussion, with a particular focus on the common problems identified in understanding and reducing health risks from disasters in multiple countries, such as the ethical and practical difficulties in decision making on evacuating vulnerable populations that arose similarly during the Fukushima nuclear disaster in 2011 and Hurricane Ike's approach to Galveston (Texas USA) in 2008. This paper also highlights the need for greater integration of research, for example through increased review and collation of evidence from different disaster settings to identify common problems and possible solutions, which was identified in this panel session as a precursor to fulfilling the goals of the Sendai Framework.Leppold C, Ochi S, Nomura S, Murray V. The Great East Japan Earthquake, tsunamis, and Fukushima Daiichi nuclear power plant disaster: lessons for evidence integration from a WADEM 2017 presentation and panel discussion. Prehosp Disaster Med. 2018;33(4):424-427.

Can a disaster affect rheumatoid arthritis status? A retrospective cohort study after the 2011 triple disaster in Fukushima, Japan.

OBJECTIVE: As status of rheumatoid arthritis (RA) is highly affected by environmental factors, a catastrophic disaster may also affect RA activity. Herein we conducted a retrospective cohort study in the disaster area of the 2011 triple disaster in Fukushima, Japan: an earthquake, tsunamis and a nuclear accident. METHODS: Clinical records of RA patients who attended a hospital near the Fukushima Daiichi Nuclear Power Plant were collected. For those who underwent whole-body counter testing, internal radiation exposure levels were also collected. As clinical parameters may fluctuate in the absence of a disaster, changes in values before and after the disaster were also compared. Logistic regression was conducted to identify factors affecting RA status. RESULTS: Fifty-three patients (average age, 64.2 years; females, 83%; average disease duration, 15.7 years) were included in the study. Five patients lived within the no-entry zone, 37 evacuated immediately after the disaster, and four temporarily stopped RA treatment. The proportions of patients who showed worsened tender joint counts, swollen joint counts and rheumatoid factor values were significantly higher after the disaster compared to those before. Among the 16 patients who underwent whole-body counter testing, only one showed a detectable, but negligible, radioactive cesium level. Use of methotrexate was identified as a possible preventive factor for RA exacerbation in this setting. CONCLUSION: This is the first study to analyze detailed profiles of RA patients after a disaster. As methotrexate may prevent disease exacerbation, continuity of care for this common chronic disease should be considered in disaster settings.

Demographic transition and factors associated with remaining in place after the 2011 Fukushima nuclear disaster and related evacuation orders.

INTRODUCTION: Demographic changes as a result of evacuation in the acute phase of the 2011 Fukushima nuclear disaster are not well evaluated. We estimated post-disaster demographic transitions in Minamisoma City-located 14-38 km north of the nuclear plant-in the first month of the disaster; and identified demographic factors associated with the population remaining in the affected areas. MATERIALS AND METHODS: We extracted data from the evacuation behavior survey administered to participants in the city between July 11, 2011 and April 30, 2013. Using mathematical models, we estimated the total population in the city after the disaster according to sex, age group, and administrative divisions of the city. To investigate factors associated with the population remaining in place after the disaster, a probit regression model was employed, taking into account sex, age, pre-disaster dwelling area, and household composition. RESULTS: The overall population decline in Minamisoma City peaked 11 days after the disaster, when the population reached 7,107 people-11% of the pre-disaster level. The remaining population levels differed by area: 1.1% for mandatory evacuation zone, 12.5% for indoor sheltering zone, and 12.6% for other areas of the city. Based on multiple regression analyses, higher odds for remaining in place were observed among men (odds ratio 1.72 [95% confidence intervals 1.64-1.85]) than women; among people aged 40-64 years (1.40 [1.24-1.58]) than those aged 75 years or older; and among those living with the elderly, aged 70 years or older (1.18 [1.09-1.27]) or those living alone (1.71 [1.50-1.94]) than among those who were not. DISCUSSION: Despite the evacuation order, some residents of mandatory evacuation zones remained in place, signaling the need for preparation to respond to their post-disaster needs. Indoor sheltering instructions may have accelerated voluntary evacuation, and this demonstrates the need for preventing potentially disorganized evacuation in future nuclear events.

The Great East Japan Earthquake: Analyses of Disaster Impacts on Health Care Clinics.

OBJECTIVE: Local health facilities play a critical role in mitigating the deterioration of health after catastrophic disasters. However, limited information is available on clinic damage. Therefore, the National Institute of Public Health conducted surveillance on clinic damage after the 2011 Great East Japan Earthquake (GEJE) to identify risk factors. METHODS: A cross-sectional study using a paper-based questionnaire was conducted that targeted 728 clinics located in coastal areas in the 3 prefectures most affected by the GEJE. RESULTS: The risk of building damage was inversely correlated with distance from the coast, whereas the risk of ceasing operations was significantly correlated with building damage and some specialties of clinics, namely, internal medicine and pediatrics.DiscussionIn mountainous countries like Japan, clinics often need to be built in coastal areas, where the majority of residents live. This surveillance revealed that clinics built in readily accessible locations and that provide care with high needs are more likely to get damaged by tsunamis. As clinics are often the frontline health facilities in disaster settings, local disaster plans need to include plans to reinforce disaster preparedness among clinics. For effective planning and resource allocation, nationwide hazard vulnerability analysis using a global standard will be helpful. (Disaster Med Public Health Preparedness. 2018; 12: 291-295).

Excess mortality due to indirect health effects of the 2011 triple disaster in Fukushima, Japan: a retrospective observational study.

BACKGROUND: Evidence on the indirect health impacts of disasters is limited. We assessed the excess mortality risk associated with the indirect health impacts of the 2011 triple disaster (earthquake, tsunami and nuclear disaster) in Fukushima, Japan. METHODS: The mortality rates in Soma and Minamisoma cities in Fukushima from 2006 to 2015 were calculated using vital statistics and resident registrations. We investigated the excess mortality risk, defined as the increased mortality risk between postdisaster and predisaster after excluding direct deaths attributed to the physical force of the disaster. Multivariate Poisson regression models were used to estimate the relative risk (RR) of mortality after adjusting for city, age and year. RESULTS: There were 6163 and 6125 predisaster and postdisaster deaths, respectively. The postdisaster mortality risk was significantly higher in the first month following the disaster (March 2011) than in the same month during the predisaster period (March 2006-2010). RRs among men and women were 2.64 (95% CI 2.16 to 3.24) and 2.46 (95% CI 1.99 to 3.03), respectively, demonstrating excess mortality risk due to the indirect health effects of the disaster. Age-specific subgroup analyses revealed a significantly higher mortality risk in women aged ≥85 years in the third month of the disaster compared with predisaster baseline, with an RR (95% CI) of 1.73 (1.23 to 2.44). CONCLUSIONS: Indirect health impacts are most severe in the first month of the disaster. Early public health support, especially for the elderly, can be an important factor for reducing the indirect health effects of a disaster.