Psychological and psychiatric symptoms of terminally ill patients with cancer and their family caregivers in the home-care setting: A nation-wide survey from the perspective of bereaved family members in Japan.

OBJECTIVE: The psychological and psychiatric symptoms of terminally ill cancer patients are highly problematic and have been associated with greater burden among caregivers. Until now, the extent of these problems in the home care setting was unclear. METHODS: This retrospective study was conducted as part of a nationwide survey from the perspective of bereaved family members in Japan (J-HOPE3). The bereaved family members rated the symptoms of delirium and suicidal ideation of patients with cancer, and the sleeplessness and depressed mood of family caregivers utilizing home care services in the one month before the patients' deaths. Regression analyses were performed to identify factors associated with caregivers' sleeplessness or depressed mood. RESULTS: Of the 532 subjects analyzed, between 17% and 65% of patients experienced various symptoms of delirium, and 27% suicidal ideation. Among family caregivers, 60% experienced sleeplessness and 35% experienced depressed mood at least once during the week. Caregivers' psychological symptoms were associated with their own poor health status, being the spouse of the patient, and the patients' psychological or psychiatric symptoms. To manage patients' symptoms, 11% of caregivers had consulted psychiatrists or psychologists while another 11% wanted to do so. CONCLUSION: Psychological problems assessed were common among patients with cancer and their family caregivers in the one month of home care prior to the patient's death. An effective complementary care system, run by home-visit physicians, nurses, and experts in mental disorders, is needed.

Trust in Physicians, Continuity and Coordination of Care, and Quality of Death in Patients with Advanced Cancer.

BACKGROUND: Provider-centered factors contribute to unexplained variation in the quality of death (QOD). The relationship between healthcare providers (HCPs) and patients, bidirectional communication, and consistency of longitudinal care planning are important provider-centered factors. OBJECTIVE: To explore whether the level of trust in HCPs, the quality of continuity of care, and the level of coordination of care among home HCPs are associated with the QOD for cancer patients dying at home. DESIGN: This study was a part of a nationwide multicenter questionnaire survey of bereaved family members of cancer patients evaluating the quality of end-of-life care in Japan. SETTING/SUBJECTS: We investigated 702 family members of cancer patients who died at home. MEASUREMENTS: The QOD was evaluated from nine core domains of the short version of the Good Death Inventory (GDI). We measured five factors on a Likert scale, including patient and family trust in HCPs, continuity of care by home hospice and hospital physicians, and coordination of care among home hospice staff. RESULTS: A total of 538 responses (77%) were obtained and 486 responses were analyzed. Trust in HCPs was correlated with the GDI score (r = 0.300-0.387, p < 0.001). The quality of care coordination was associated with the GDI score (r = 0.242, p < 0.001). CONCLUSIONS: Trust of the patient and family in home hospice staff, as well as coordination of care among hospice staff, are associated with the QOD for cancer patients dying at home.

Family caregivers require mental health specialists for end-of-life psychosocial problems at home: a nationwide survey in Japan.

BACKGROUND: Psychological distress is problematic for patients and their family caregivers in the oncological setting. The level of stress is influenced by the health status of the patient and their family members as well as the support system for home care. However, it remains unclear how best to support distressed caregivers providing end-of-life care at home. METHODS: The present study was performed as part of the Japan Hospice and Palliative Care Evaluation study among caregivers whose family members are provided home palliative care. The caregivers were asked whether they wished to receive psychological support from mental health specialists, and factors associated with the need for psychological support were analyzed. RESULTS: Of the 1052 caregivers, 628 completed the questionnaire. As a whole, 169 subjects [27%; 23-30% (95% confidence interval)] reported needing psychological support from a mental health specialist. According to a multiple regression analysis, factors associated with the need for psychological support included (1) emotional distress due to the need to adapt to rapid worsening of the patient's condition [adjusted odds ratio: 2.62 (95% CI 1.77-3.88), p < 0.001], (2) the poor health conditions of the caregivers [2.93 (1.61-5.36), p < 0.001], and (3) having someone else available to care for the patient in place of the caregiver [0.51 (0.34-0.78), p = 0.002]. CONCLUSIONS: Psychological support is required for caregivers tending to patients at home. Further studies are needed to construct a system to provide continuous support to caregivers. Copyright © 2015 John Wiley & Sons, Ltd.

Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task.

BACKGROUND: Late adolescents are under increased risk of developing depressive symptoms. Behavioral activation is an effective treatment for subthreshold depression, which can prevent the development of subthreshold depression into a major depressive disorder. However, the neural mechanisms underlying the efficacy of behavioral activation have not been clearly understood. We investigated neural responses during reward processing by individuals with subthreshold depression to clarify the neural mechanisms of behavioral activation. METHODS: Late adolescent university students with subthreshold depression (n=15, age 18-19 years) as indicated by a high score on the Beck's Depression Inventory-ll (BDI-ll) and 15 age-matched controls with a low BDI-ll score participated in functional magnetic resonance imaging scanning conducted during a monetary incentive delay task on two occasions. The Individuals in the subthreshold depression group received five, weekly behavioral activation sessions between the two scanning sessions. Moreover, they did not receive any medication until the study was completed. RESULTS: Behavioral activation significantly reduced depressive symptoms. Moreover, compared to the changes in brain functions in the control group, the behavioral activation group showed functional changes during loss anticipation in brain structures that mediates cognitive and emotional regulation, including the left ventrolateral prefrontal cortex and angular gyrus. LIMITATIONS: Replication of the study with a larger sample size is required to increase the generalizability of these results. CONCLUSIONS: Behavioral activation results in improved functioning of the fronto-parietal region during loss anticipation. These results increase our understanding of the mechanisms underlying specific psychotherapies.

Direct and indirect influences of childhood abuse on depression symptoms in patients with major depressive disorder.

BACKGROUND: It is known that the onset, progression, and prognosis of major depressive disorder are affected by interactions between a number of factors. This study investigated how childhood abuse, personality, and stress of life events were associated with symptoms of depression in depressed people. METHODS: Patients with major depressive disorder (N = 113, 58 women and 55 men) completed the Beck Depression Inventory-II (BDI-II), the Neuroticism Extroversion Openness Five Factor Inventory (NEO-FFI), the Child Abuse and Trauma Scale (CATS), and the Life Experiences Survey (LES), which are self-report scales. Results were analyzed with correlation analysis and structural equation modeling (SEM), by using SPSS AMOS 21.0. RESULTS: Childhood abuse directly predicted the severity of depression and indirectly predicted the severity of depression through the mediation of personality. Negative life change score of the LES was affected by childhood abuse, however it did not predict the severity of depression. CONCLUSIONS: This study is the first to report a relationship between childhood abuse, personality, adulthood life stresses and the severity of depression in depressed patients. Childhood abuse directly and indirectly predicted the severity of depression. These results suggest the need for clinicians to be receptive to the possibility of childhood abuse in patients suffering from depression. SEM is a procedure used for hypothesis modeling and not for causal modeling. Therefore, the possibility of developing more appropriate models that include other variables cannot be excluded.

[Talking about home hospices with terminally ill cancer patients -- a multicenter survey of bereaved families].

INTRODUCTION: Communicating with patients is clearly an integral part of physicians' practice, and introducing home hospice care is sometimes a difficult task for oncologists. The primary aims of this study were to clarify family-reported degree of emotional distress and the necessity for improvement in communication when introducing home hospice care, and to identify factors contributing to distress levels. METHODS: A multicenter questionnaire survey was conducted involving 1,052 family members of cancer patients who died at home at 15 home-based hospice services throughout Japan. RESULTS: A total of 616 responses were analyzed(effective response rate of 60%). Fifty-nine percent of the bereaved family members reported that they were distressed or very distressed in receiving information about home hospice care, and 30% reported considerable or much improvement was necessary. There were 6 determinants of family-reported degree of emotional distress and the necessity for improvement: 1 ) Family distress was experienced when the physician stated that the disease progression defeated medicine and nothing could be done for the patient. 2 ) The physicians' explanation did not match with the state of family preparation. 3 ) There was no intimacy between hospital physician and home physician. 4 ) Physicians did not make the atmosphere relaxing enough to allow families to ask questions. 5 ) Nurses did not follow up to generate additional ideas to supplement the physician's statement. 6 ) Family members experienced pressure to make a rash decision. CONCLUSION: In receiving information about transition of home care, a considerable number of families experienced high levels of emotional distress and felt a need for improvement in the communication style. This study proposes 6 strategies to alleviate family distress.

Length of home hospice care, family-perceived timing of referrals, perceived quality of care, and quality of death and dying in terminally ill cancer patients who died at home.

PURPOSE: This study aims to clarify the length of home hospice care, family-perceived timing of referrals, and their effects on the family-perceived quality of care and quality of death and dying of terminally ill cancer patients who died at home and identify the determinants of perceived late referrals. METHODS: A multicenter questionnaire survey was conducted involving 1,052 family members of cancer patients who died at home supported by 15 home-based hospice services throughout Japan. RESULTS: A total of 693 responses were analyzed (effective response rate, 66 %). Patients received home-based hospice care for a median of 35.0 days, and 8.0 % received home hospice care for less than 1 week. While 1.5 % of the families reported the timing of referrals as early, 42 % reported the timing as late or too late. The families of patients with a length of care of less than 4 weeks were more likely to regard the timing of referrals as late or too late. The patients of family members who regarded the timing of referrals as late or too late had a significantly lower perceived quality of care (effect size, 0.18; P = 0.039) and lower quality of death and dying (effect size, 0.15, P = 0.063). Independent determinants of higher likelihoods of perceived late referrals included: frequent visits to emergency departments, patient being unprepared for worsening condition, and patient having concerns about relationship with new doctor. Discharge nurse availability was independently associated with lower likelihoods of perceived late referrals. CONCLUSIONS: A significant number of bereaved families regarded the timing of referrals to home hospices as late, and the perceived timing was associated with the family-perceived quality of care and quality of death and dying. Systematic strategies to overcome the barriers related to perceived late referrals are necessary.

Neural basis of anticipatory anxiety reappraisals.

Reappraisal is a well-known emotion regulation strategy. Recent neuroimaging studies suggest that reappraisal recruits both medial and lateral prefrontal brain regions. However, few studies have investigated neural representation of reappraisals associated with anticipatory anxiety, and the specific nature of the brain activity underlying this process remains unclear. We used functional magnetic resonance imaging (fMRI) to investigate neural activity associated with reappraisals of transient anticipatory anxiety. Although transient anxiety activated mainly subcortical regions, reappraisals targeting the anxiety were associated with increased activity in the medial and lateral prefrontal regions (including the orbitofrontal and anterior cingulate cortices). Reappraisal decreased fear circuit activity (including the amygdala and thalamus). Correlational analysis demonstrated that reductions in subjective anxiety associated with reappraisal were correlated with orbitofrontal and anterior cingulate cortex activation. Reappraisal recruits medial and lateral prefrontal regions; particularly the orbitofrontal and anterior cingulate cortices are associated with successful use of this emotion regulation strategy.

Distinctive spontaneous regional neural activity in patients with somatoform pain disorder: a preliminary resting-state fMRI study.

This resting-state functional magnetic resonance imaging study found that nine patients with somatoform pain disorder exhibited atypical precentral gyrus activation compared with 20 healthy controls. The role of the precentral gyrus in pain-related processing is discussed.

Hippocampal activation during associative encoding of word pairs and its relation to symptomatic improvement in depression: a functional and volumetric MRI study.

BACKGROUND: Altered emotional memory is one of the core cognitive functions that causes and maintains depression. Although many studies have investigated the relationship between hippocampal volume, depression and treatment response, no studies have investigated the relationship for hippocampal activity. Additionally, few studies have examined the relationship between functional and structural abnormalities in depression. METHODS: We conducted a functional and volumetric MRI study investigating associative encoding of positive, negative and neutral word pairs in 13 healthy controls, and 14 untreated depressives. We carried out fMRI during a memory-encoding task at baseline. Treatment response was clinically assessed six weeks after pharmacotherapy began. Then, we explored the relation between brain activation during encoding of each word pair and symptomatic improvement. RESULTS: Relative to controls, depressives exhibited decreased activity in the left hippocampus during encoding positive word pairs and, in contrast, increased activity in the right hippocampus during encoding negative or neutral word pairs. Poor response to treatment was associated with smaller activation within the left hippocampus during the memory encoding of positive word pairs. Overall results were not confounded by hippocampal volume. LIMITATIONS: We could not appreciate any disease alteration during the retrieving phase. CONCLUSION: We found qualitative differences in hippocampus functioning between depressives and healthy controls. In addition, the left hippocampus could have an effect on treatment response in depression by contributing to the dysfunctional encoding of positive information.

Assessment of reasons for referral and activities of hospital palliative care teams using a standard format: a multicenter 1000 case description.

CONTEXT: The many benefits of hospital palliative care teams (PCTs) are well known. However, their specific activities have not been fully clarified, and no standardized methods for reporting PCT activities are available. OBJECTIVES: The aim of this study was to investigate, through the use of a standard format, the activities performed by hospital PCTs in Japan. METHODS: This was a prospective observational study. A total of 21 hospital PCTs were included in this study, and each recruited approximately 50 consecutively referred patients. Participating PCTs filled in a standard form for reporting activities. RESULTS: We obtained data from 1055 patients who were referred to PCTs. Of the 1055 patients, 1005 patients (95%) had cancer. The median number of reasons for referral and problems identified by PCTs was two (0-22) and four (0-18), respectively. The two major reasons for referral were pain (63%) and anxiety/depression/grief/emotional burden (22%). The major recommendations were pharmacological treatment (74%), care for the patient's physical symptoms (49%), and support for patient's decision making (38%). The major activities performed by the PCTs were comprehensive assessment (90%), care for the patient's physical symptoms (77%), and pharmacological treatment (74%). CONCLUSION: The components of hospital PCT activities were successfully measured using the Standard Format for Reporting Hospital PCT Activity. The results of this study and the format for reporting hospital PCT activity could be effective in improving hospital PCT practice and for the education of new hospital PCT members.

Continuous intravenous infusion of ketamine and lidocaine as adjuvant analgesics in a 5-year-old patient with neuropathic cancer pain.

For difficult to treat neuropathic pain from cancer, adjuvant analgesics are often used with opioids. We present the case of a 5-year-old girl who was diagnosed with meningitis caused by malignant T-cell lymphoma. She had severe neuropathic pain not relieved by increasing doses of a fentanyl infusion. Intravenous administration of ketamine and lidocaine in combination with fentanyl provided excellent analgesia without significant side effects. Ketamine and lidocaine can be safely infused together with concomitant opioids for the treatment of refractory neuropathic pain caused by cancer.

Serum brain-derived neurotrophic factor and antidepressant-naive major depression after lung cancer diagnosis.

Previous studies have reported the existence of an association between brain-derived neurotrophic factor and major depression. However, the possible role of brain-derived neurotrophic factor in the pathophysiology of major depression after cancer diagnosis has not yet been investigated. Subjects were collected using the Lung Cancer Database project. Using the cut-off scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), 81 subjects with depression (HADS-D > 10) and 81 subjects without depression (HADS-D < 5) were selected. The two groups were matched for age, sex, clinical stage and performance status. The serum brain-derived neurotrophic factor levels were measured using an enzyme-linked immunosorbent assay method. The serum brain-derived neurotrophic factor levels were not statistically different between the subjects in the depression group [29.1 (13.6) ng/ml; mean (SD)] and the non-depression group [31.4 (10.6) ng/ml] (P = 0.22). In a stratified analysis by gender, however, the mean serum brain-derived neurotrophic factor level in the depression group tended to be lower than that in the non-depression group among women (n = 24 pairs, P = 0.06). Major depression after cancer diagnosis is not associated with serum brain-derived neurotrophic factor levels.

Regional cerebral glucose metabolism in patients with secondary depressive episodes after fatal pancreatic cancer diagnosis.

BACKGROUND: Secondary depression is common in the clinical oncology setting after pancreatic cancer diagnosis, following which the patients have to face the fact that they have a cancer with an extremely poor prognosis. However, the specific pathophysiology remains unclear. The present study examined the regional cerebral glucose metabolism using F18-fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) in antidepressant-naïve pancreatic cancer patients with a depressive episode after their cancer diagnosis and before their cancer treatment. METHODS: Regional cerebral glucose metabolism in pancreatic cancer patients without any antidepressant medication after the cancer diagnosis was measured with F18-FDG PET. A depressive episode after the cancer diagnosis was defined as including major and minor depressive episodes, and was diagnosed using the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV). The prefrontal and limbic regions were the primary regions-of-interest, and an uncorrected value of p<0.005 was used as significant. RESULTS: Six of 21 pancreatic cancer patients were diagnosed as having a depressive episode. Significantly higher glucose metabolism in depressed patients was found in the subgenual anterior cingulate cortex (sACC) (uncorrected p=0.002). LIMITATIONS: There was a small number of subjects, and there were no healthy controls. CONCLUSIONS: The higher metabolism in the sACC may be associated with the pathophysiology of secondary depressive episodes in patients following pancreatic cancer diagnosis.

Psychometric properties of the Japanese version of the Quality Of Life-Cancer Survivors Instrument.

The purpose of this study was to describe the psychometric properties of the Japanese version of the Quality of Life-Cancer Survivors Instrument (QOL-CS-J) developed in the U.S. This study was conducted as a mail survey to survivors of more than 5 years post curative resection for non-small-cell lung cancer (NSCLC) and who had participated in an earlier survey. This survey included the medical and demographic factors, the QOL-CS scores, and the Medical Outcome Study 36-Item Short Form (SF-36). A total of 113 survivors completed the survey. To confirm the reliability, the Cronbach's alpha coefficient of each subscale was calculated as an internal consistency (alpha = 0.65-0.89). To confirm the validity of the trial as conducted, Pearson's correlation coefficients between the subscales of the QOL-CS and the subscales of the SF-36 were calculated. There were moderate correlations between associated subscales including QOL-CS physical to SF-36 bodily pain (r = 0.45) and vitality (r = 0.52), QOL-CS psychological to SF-36 mental health (r = 0.55), QOL-CS social to SF-36 general health perception (r = 0.31) and mental health (r = 0.47), and QOL-CS total to each subscale of SF-36 (r = 0.25-0.64). Findings demonstrated that the QOL-CS-J adequately measured the QOL in long-term NSCLC survivors.

Cavum septi pellucidi and intrusive recollections in cancer survivors.

A previous study reported abnormally large cavum septi pellucidi (CSP) in posttraumatic stress disorder (PTSD). We utilized magnetic resonance imaging to examine the frequency of large CSP, as defined by Nopoulos et al. (1997), in cancer survivors with and without intrusive recollections in a sample identical to that of our previous study. The frequency of large CSP did not differ between the two groups. The results suggest that alteration in midline structures during the course of neurodevelopment may lead to severe PTSD, while subthreshold PTSD, such as intrusive recollections, appear not to be associated with such alterations.

Depression and survival in patients with non-small cell lung cancer after curative resection: a preliminary study.

Psychological depression is thought to be a predictor of poor survival among cancer patients. The objective of the present study was to investigate the association between depression and survival in surgically treated Japanese patients with non-small cell lung cancer (NSCLC). From June 1996 through April 1999, a total of 229 patients with postoperative lung cancer were enrolled. Three months after the patients' surgery, the Structured Clinical Interview for DSM-III-R (SCID) and the Profile of Mood States (POMS) were used to assess the patient for depression, based on the interviewers' rating and a self-report, respectively. The follow-up period consisted of a total of 14 342 person-months (median=69 months). As of January 2004, 55 deaths had occurred within the follow-up period. A Cox regression was used to estimate the hazard ratio (HR) of mortality adjusting for age, sex, smoking status, occasion of diagnosis, pathological stage and preoperative percentage forced expiratory volume in 1 s. The depression-dejection subscale on the POMS was divided into three score levels. The multivariate HR of survival for individuals with depression, as diagnosed by the SCID, was 2.2 (95% confidence interval 0.8-6.0) (P-value=0.14), compared with individuals without depression. The multivariate HR of survival for subjects in the highest level of the POMS Depression-Dejection subscale was 1.4 (0.7-2.6), compared with in the lowest level (trend P-value=0.0502). This prospective cohort study in Japan does not support the hypothesis that depression is associated with survival among NSCLC patients after curative resection, but further analysis involving a long-term follow-up period is needed.

Marital status, social support and survival after curative resection in non-small-cell lung cancer.

It has been suggested that marital status and social support are associated with survival in cases of lung cancer, and that such an association may be mediated by several factors. In this prospective cohort study, we investigated the effect of marital status and social support on survival after curative resection for non-small cell lung carcinoma (NSCLC) in Japan. From June 1996 to April 1999, a total of 238 patients with resectable NSCLC were enrolled. Marital status and social support were assessed. The presence and absence of confidants and the satisfaction level with the confidants were used as factors reflecting social support. During the follow-up period, 57 deaths from all causes were identified through January 2004. For the statistical analysis, Cox proportional hazards regression analyses were used. With regard to marital status, the multivariable adjusted hazard ratio (HR) of unmarried patients versus married patients was 0.8 (95% confidence interval, 0.3-1.8) (P-value=0.53) after controlling for potential confounding factors, including age, sex, occasion of cancer diagnosis, pathological stage, smoking status, smoking status after surgery and serum albumin level. Similarly, the multivariable adjusted HR of patients without confidants versus those with confidants was 1.0 (0.5-2.2) (P-value=0.90), whereas the multivariable adjusted HR of the dissatisfied-with-confidants group versus the satisfied-with-confidants group was 0.7 (0.4-1.3) (P-value=0.28). The present data do not support the hypothesis that marital status and social support are associated with survival in NSCLC.

Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis.

BACKGROUND: Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. METHODS: Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. RESULTS: Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. CONCLUSIONS: It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.