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1.  A mindfulness-based stress management program and treatment with omega-3 fatty acids to maintain a healthy mental state in hospital nurses (Happy Nurse Project): study protocol for a randomized controlled trial 
Trials  2015;16:36.
It is reported that nursing is one of the most vulnerable jobs for developing depression. While they may not be clinically diagnosed as depressed, nurses often suffer from depression and anxiety symptoms, which can lead to a low level of patient care. However, there is no rigorous evidence base for determining an effective prevention strategy for these symptoms in nurses. After reviewing previous literature, we chose a strategy of treatment with omega-3 fatty acids and a mindfulness-based stress management program for this purpose. We aim to explore the effectiveness of these intervention options for junior nurses working in hospital wards in Japan.
A factorial-design multi-center randomized trial is currently being conducted. A total of 120 nurses without a managerial position, who work for general hospitals and gave informed consent, have been randomly allocated to a stress management program or psychoeducation using a leaflet, and to omega-3 fatty acids or identical placebo pills. The stress management program has been developed according to mindfulness cognitive therapy and consists of four 30-minute individual sessions conducted using a detailed manual. These sessions are conducted by nurses with a managerial position. Participants allocated to the omega-3 fatty acid groups are provided with 1,200 mg/day of eicosapentaenoic acid and 600 mg/day of docosahexaenoic acid for 90 days.
The primary outcome is the change in the total score of the Hospital Anxiety and Depression Scale (HADS), determined by a blinded rater via the telephone at week 26. Secondary outcomes include the change in HADS score at 13 and 52 weeks; presence of a major depressive episode; severity of depression, anxiety, insomnia, burnout, and presenteeism; utility scores and adverse events at 13, 26 and 52 weeks.
An effective preventive intervention may not only lead to the maintenance of a healthy mental state in nurses, but also to better quality of care for inpatients. This paper outlines the background and methods of a randomized trial that evaluates the possible additive value of omega-3 fatty acids and a mindfulness-based stress management program for reducing depression in nurses.
Trial registration NCT02151162 (registered on 27 May 2014).
PMCID: PMC4326519  PMID: 25636180
Anxiety; Behavior therapy; Depression; Fatty acids; Omega-3; Mindfulness; Prevention and control
2.  Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy 
Cancer Medicine  2014;3(3):702-709.
Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = −2.6626 to −0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels.
PMCID: PMC4101762  PMID: 24756915
Breast cancer; cognitive impairment; interleukin-6; radiotherapy; Wechsler Memory Scale-Revised
3.  Associations between Disaster Exposures, Peritraumatic Distress, and Posttraumatic Stress Responses in Fukushima Nuclear Plant Workers following the 2011 Nuclear Accident: The Fukushima NEWS Project Study 
PLoS ONE  2014;9(2):e87516.
The 2011 Fukushima Daiichi Nuclear Power Plant accident was the worst nuclear disaster since Chernobyl. The nearby Daini plant also experienced substantial damage but remained intact. Workers for the both plants experienced multiple stressors as disaster victims and workers, as well as the criticism from the public due to their company's post-disaster management. Little is known about the psychological pathway mechanism from nuclear disaster exposures, distress during and immediately after the event (peritraumatic distress; PD), to posttraumatic stress responses (PTSR).
A self-report questionnaire was administered to 1,411 plant employees (Daiichi, n = 831; Daini, n = 580) 2–3 months post-disaster (total response rate: 80.2%). The socio-demographic characteristics and disaster-related experiences were assessed as independent variables. PD and PTSR were measured by the Japanese versions of Peritraumatic Distress Inventory and the Impact of Event Scale-Revised, respectively. The analysis was conducted separately for the two groups. Bivariate regression analyses were performed to assess the relationships between independent variables, PD, and PTSR. Significant variables were subsequently entered in the multiple regression analyses to explore the pathway mechanism for development of PTSR.
For both groups, PTSR highly associated with PD (Daiichi: adjusted β, 0.66; p<0.001; vs. Daini: adjusted β, 0.67; p<0.001). PTSR also associated with discrimination/slurs experience (Daiichi: 0.11; p<0.001; vs. Daini, 0.09; p = 0.005) and presence of preexisting illness(es) (Daiichi: 0.07; p = 0.005; vs. Daini: 0.15; p<.0001). Other disaster-related variables were likely to be associated with PD than PTSR.
Among the Fukushima nuclear plant workers, disaster exposures associated with PD. PTSR was highly affected by PD along with discrimination/slurs experience.
PMCID: PMC3929434  PMID: 24586278
4.  Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial 
BMC Psychiatry  2013;13:8.
Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial.
The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012.
This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people.
Trial registration Identifier NCT00671099
PMCID: PMC3598223  PMID: 23289548
Fish oil; Omega-3 fatty acid; Docosahexaenoic acid; Eicosapentaenoic acid; Posttraumatic stress disorder; Accidental injury; Prevention
6.  Potential impact of propofol immediately after motor vehicle accident on later symptoms of posttraumatic stress disorder at 6-month follow up: a retrospective cohort study 
Critical Care  2012;16(5):R196.
Critically injured patients are at risk of developing posttraumatic stress disorder (PTSD). Propofol was recently reported to enhance fear memory consolidation retrospectively. Thus, we investigated here whether administration of propofol within 72 h of a motor vehicle accident (MVA) affects the subsequent development of PTSD symptoms.
We examined data obtained from a prospective cohort study of MVA-related injured patients, admitted to the intensive care unit of a general hospital. We investigated the effect of propofol administration within 72 h of MVA on outcome. Primary outcome was diagnosis of full or partial PTSD as determined by the Clinician-Administered PTSD Scale (CAPS) at 6 months. Secondary outcomes were diagnosis of full or partial PTSD at 1 month and CAPS score indicating PTSD at 1 and 6 months. Multivariate analysis was conducted adjusting for being female, age, injury severity score (ISS), and administration of ketamine or midazolam within 72 h of MVA.
Among 300 patients recruited (mean ISS, 8.0; median Glasgow Coma Scale (GCS) score, 15.0; age, 18 to 69 years), propofol administration showed a higher risk for full or partial PTSD as determined by CAPS at 6 months (odds ratio = 6.13, 95% confidence interval (CI): 1.57 to 23.85, P = 0.009) and at 1 month (odds ratio = 1.31, 95% CI: 0.41 to 4.23, P = 0.647) in the multivariate logistic regression. Multivariate regression analysis showed a trend toward adverse effects of propofol on PTSD symptom development at 6 months after MVA (β = 4.08, 95% CI: -0.49 to 8.64, P = 0.080), but not at 1 month after MVA (β = -0.42, 95% CI: -6.34 to 5.51, P = 0.890).
These findings suggest that using propofol in the acute phase after MVA might be associated with the development of PTSD symptoms 6 months later. However, since the design of this study was retrospective, these findings should be interpreted cautiously and further study is warranted.
PMCID: PMC3682298  PMID: 23075426
7.  Fish consumption and cardiovascular response during mental stress 
BMC Research Notes  2012;5:288.
Frequent fish consumption is related to a lower risk of coronary heart disease. However, the physiological mechanisms underlying this cardioprotective effect are as yet unknown. We therefore examined certain cardiovascular physiological variables of fish eaters during rest, whilst conducting mental arithmetic, and during recovery.
The participants were 12 fish eaters (eating baked fish more than 3–4 times/week) and 13 controls (eating fish less than 1–2 times/week). Analysis of the collected data revealed that heart rate, blood pressure, and pulse wave velocity were significantly lower and pre-ejection period and baroreflex sensitivity were significantly higher in the fish eaters than in the controls during both rest and mental arithmetic, and that systolic and mean blood pressure recovery from mental arithmetic were faster in the fish eaters than in the controls.
These findings suggest a possible physiological mechanism that may explain why frequent fish consumption reduces coronary heart disease risk.
PMCID: PMC3414797  PMID: 22695000
Fish consumption; Hemodynamics; Impedance cardiography; Arterial stiffness; Coronary heart diseases; Omega-3 fatty acids
8.  Concern over radiation exposure and psychological distress among rescue workers following the Great East Japan Earthquake 
BMC Public Health  2012;12:249.
On March 11, 2011, the Great East Japan Earthquake and tsunami that followed caused severe damage along Japans northeastern coastline and to the Fukushima Daiichi nuclear power plant. To date, there are few reports specifically examining psychological distress in rescue workers in Japan. Moreover, it is unclear to what extent concern over radiation exposure has caused psychological distress to such workers deployed in the disaster area.
One month after the disaster, 424 of 1816 (24%) disaster medical assistance team workers deployed to the disaster area were assessed. Concern over radiation exposure was evaluated by a single self-reported question. General psychological distress was assessed with the Kessler 6 scale (K6), depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), fear and sense of helplessness with the Peritraumatic Distress Inventory (PDI), and posttraumatic stress symptoms with the Impact of Event Scale-Revised (IES-R).
Radiation exposure was a concern for 39 (9.2%) respondents. Concern over radiation exposure was significantly associated with higher scores on the K6, CES-D, PDI, and IES-R. After controlling for age, occupation, disaster operation experience, duration of time spent watching earthquake news, and past history of psychiatric illness, these associations remained significant in men, but did not remain significant in women for the CES-D and PDI scores.
The findings suggest that concern over radiation exposure was strongly associated with psychological distress. Reliable, accurate information on radiation exposure might reduce deployment-related distress in disaster rescue workers.
PMCID: PMC3352263  PMID: 22455604
9.  Peritraumatic Distress, Watching Television, and Posttraumatic Stress Symptoms among Rescue Workers after the Great East Japan Earthquake 
PLoS ONE  2012;7(4):e35248.
The Great East Japan Earthquake of March 11, 2001 left around 20,000 dead or missing. Previous studies showed that rescue workers, as well as survivors, of disasters are at high risk for posttraumatic stress disorder (PTSD). This study examined the predictive usefulness of the Peritraumatic Distress Inventory (PDI) among rescue workers of Disaster Medical Assistance Teams (DMATs) deployed during the acute disaster phase of the Great East Japan Earthquake.
Methodology/Principal Findings
In this prospective observational study, the DMAT members recruited were assessed 1 month after the earthquake on the PDI and 4 months after the earthquake on the Impact of Event Scale-Revised to determine PTSD symptoms. The predictive value of the PDI at initial assessment for PTSD symptoms at the follow-up assessment was examined by univariate and multiple linear regression analysis. Of the 254 rescue workers who participated in the initial assessment, 173 completed the follow-up assessment. Univariate regression analysis revealed that PDI total score and most individual item scores predicted PTSD symptoms. In particular, high predictive values were seen for peritraumatic emotional distress such as losing control of emotions and being ashamed of emotional reactions. In multiple linear regression analysis, PDI total score was an independent predictor for PTSD symptoms after adjusting for covariates. As for covariates specifically, watching earthquake television news reports for more than 4 hours per day predicted PTSD symptoms.
The PDI predicted PTSD symptoms in rescue workers after the Great East Japan Earthquake. Peritraumatic emotional distress appears to be an important factor to screen for individuals at risk for developing PTSD among medical rescue workers. In addition, watching television for extended period of time might require attention at a time of crisis.
PMCID: PMC3338412  PMID: 22558130
10.  Attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among disaster medical assistance team members after the Great East Japan Earthquake: The APOP randomized controlled trial 
BMC Psychiatry  2011;11:132.
On March 11, 2011, a magnitude 9.0 earthquake, the most powerful ever recorded in Japan, and a massive tsunami struck off the coast of the Sanriku region. A Disaster Medical Assistance Team, a mobile medical team with specialized training that is deployed during the acute phase of a disaster, was dispatched to areas with large-scale destruction and multiple injured and sick casualties. Previous studies have reported critical incident stress (i.e. posttraumatic stress disorder symptoms and depressive symptoms) among rescue workers as well as the need for screening and prevention for posttraumatic stress disorder. So far we have shown in an open trial that posttraumatic stress disorder symptoms in critically injured patients can be reduced by taking omega-3 fatty acids intended to stimulate hippocampal neurogenesis.
This study is designed to determine the effectiveness of attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among Disaster Medical Assistance Team members after the Great East Japan Earthquake, and is named the APOP randomized controlled trial which is currently ongoing. First, we will provide psycho-education on posttraumatic distress, which is common in responders to the Disaster Medical Assistance Team members deployed to the disaster area. Second, observational research will be conducted to evaluate critical incident stress following the completion of medical activities. Third, team members who provide consent to participate in the intervention research will be randomly divided into a group given an omega-3 fatty acid supplement and a group not given the supplements. Outcome will be evaluated at 12 weeks after the supplements are shipped to the team members.
Measures that address critical incident stress in disaster responders are important, but there is no substantial evidence that links such measures with prevention of posttraumatic stress disorder. Thus, any confirmation through this study that the intake of omega-3 fatty acid supplements serves as a simple preventative measure for critical incident stress will be of great significance.
Trial registration
UMIN Clinical Trials Registry, UMIN000005367
PMCID: PMC3167761  PMID: 21846343
11.  Clearance of fear memory from the hippocampus through neurogenesis by omega-3 fatty acids: a novel preventive strategy for posttraumatic stress disorder? 
Not only has accidental injury been shown to account for a significant health burden on all populations, regardless of age, sex and geographic region, but patients with accidental injury frequently present with the psychiatric condition of posttraumatic stress disorder (PTSD). Prevention of accident-related PTSD thus represents a potentially important goal. Physicians in the field of psychosomatic medicine and critical care medicine have the opportunity to see injured patients in the immediate aftermath of an accident. This article first briefly reviews the prevalence and associated factors of accident-related PTSD, then focuses on a conceptual model of fear memory and proposes a new, rationally hypothesized translational preventive intervention for PTSD through promoting hippocampal neurogenesis by omega-3 fatty acid supplementation. The results of an open-label pilot trial of injured patients admitted to the intensive care unit suggest that omega-3 fatty acid supplementation immediately after accidental injury can reduce subsequent PTSD symptoms.
PMCID: PMC3045887  PMID: 21303552
12.  Reliability and validity of the Japanese version of the Resilience Scale and its short version 
BMC Research Notes  2010;3:310.
The clinical relevance of resilience has received considerable attention in recent years. The aim of this study is to demonstrate the reliability and validity of the Japanese version of the Resilience Scale (RS) and short version of the RS (RS-14).
The original English version of RS was translated to Japanese and the Japanese version was confirmed by back-translation. Participants were 430 nursing and university psychology students. The RS, Center for Epidemiologic Studies Depression Scale (CES-D), Rosenberg Self-Esteem Scale (RSES), Social Support Questionnaire (SSQ), Perceived Stress Scale (PSS), and Sheehan Disability Scale (SDS) were administered. Internal consistency, convergent validity and factor loadings were assessed at initial assessment. Test-retest reliability was assessed using data collected from 107 students at 3 months after baseline. Mean score on the RS was 111.19. Cronbach's alpha coefficients for the RS and RS-14 were 0.90 and 0.88, respectively. The test-retest correlation coefficients for the RS and RS-14 were 0.83 and 0.84, respectively. Both the RS and RS-14 were negatively correlated with the CES-D and SDS, and positively correlated with the RSES, SSQ and PSS (all p < 0.05), although the correlation between the RS and CES-D was somewhat lower than that in previous studies. Factor analyses indicated a one-factor solution for RS-14, but as for RS, the result was not consistent with previous studies.
This study demonstrates that the Japanese version of RS has psychometric properties with high degrees of internal consistency, high test-retest reliability, and relatively low concurrent validity. RS-14 was equivalent to the RS in internal consistency, test-retest reliability, and concurrent validity. Low scores on the RS, a positive correlation between the RS and perceived stress, and a relatively low correlation between the RS and depressive symptoms in this study suggest that validity of the Japanese version of the RS might be relatively low compared with the original English version.
PMCID: PMC2993730  PMID: 21083895
13.  Posttraumatic growth, posttraumatic stress disorder and resilience of motor vehicle accident survivors 
Although some previous studies have suggested that posttraumatic growth (PTG) is comprised of several factors with different properties, few have examined both the association between PTG and posttraumatic stress disorder (PTSD) and between PTG and resilience, focusing on each of the factors of PTG. This study aimed to examine the hypothesis that some factors of PTG, such as personal strength, relate to resilience, whereas other factors, such as appreciation of life, relate to PTSD symptoms among Japanese motor vehicle accident (MVA) survivors.
This cross-sectional study was performed with 118 MVA survivors at 18 months post MVA. Data analyzed included self-reporting questionnaire scores on the Posttraumatic Growth Inventory (PTGI), the Impact of Event Scale- Revised (IES-R), and the Sense of Coherence (SOC) scale, which is one of the most widely used scales for measuring resilience. Correlations between scores on the PTGI and IES-R, the PTGI and SOC scale, and the IES-R and SOC scale were established by calculating Spearman's correlation coefficients.
PTGI was positively correlated with both SOC and PTSD symptoms, in spite of an inverse relationship between SOC and PTSD symptoms. Relating to others, new possibilities, and personal strength on the PTGI were correlated positively with SOC, and spiritual change and appreciation of life on the PTGI were positively correlated with PTSD symptoms.
Some factors of PTG were positively correlated with resilience, which can be regarded as an outcome of coping success, whereas other factors of PTG were positively correlated with PTSD symptoms, which can be regarded as signifying coping effort in the face of enduring distress. These findings contribute to our understanding of the psychological change experienced by MVA survivors, and to raising clinicians' awareness of the possibility that PTG represents both coping effort coexisting with distress and outcome of coping success.
PMCID: PMC2914073  PMID: 20573276
14.  A randomized controlled multicenter trial of post-suicide attempt case management for the prevention of further attempts in Japan (ACTION-J) 
BMC Public Health  2009;9:364.
A previous suicide attempt is a potent risk factor for suicide later on. Crisis intervention, psychiatric and psychosocial evaluation at emergency medical facilities, and follow-up care for suicide attempters are considered important components for suicide prevention. The Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) includes a randomized, controlled, multicenter trial of post-suicide attempt case management for the prevention of further attempts (ACTION-J) to address the continuing increase in suicides in Japan. The primary aim of ACTION-J is to examine the effectiveness of an extensive intervention for suicide attempters in prevention of recurrent suicidal behavior, as compared with standard intervention. This paper describes the rationale and protocol of the ACTION-J trial.
In this clinical trial, case management intervention will be provided at 19 emergency medical facilities in Japan. After crisis intervention including psychiatric evaluation, psychosocial assessment, and psychological education, subjects will be randomly assigned to either a group receiving continuous case management or a control group receiving standard care. Suicidal ideation, depressive symptoms, and general health condition will be evaluated as secondary measures. The intervention was initiated in July 2006. By December, 2009, 842 subjects will be randomized. Subject follow-up will continue for 1.5 to 5 years.
Suicide is a complex phenomenon that encompasses multiple factors. Case management by multi-sector collaboration is needed. ACTION-J may provide valuable information on suicide attempters and may develop effective case management to reduce future risk for suicide attempters.
Trial registration
UMIN Clinical Trials Registry number, UMIN000000444. number, NCT00736918.
PMCID: PMC2760885  PMID: 19781096

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