Association between experiences of advanced cancer patients at the end of life and depression in their bereaved caregivers.

OBJECTIVE: Research on the association between circumstances of death in advanced cancer patients and depression in their bereaved caregivers is limited. METHODS: A longitudinal study was performed on patients admitted to 21 inpatient hospices/palliative care units (PCUs) in Japan. Patient symptoms were assessed at admission and in the last 3 days of life. Data on distressing events (unexpected death, bleeding) and received treatments (morphine prescriptions, continuous deep sedation, cardiopulmonary resuscitation) were also obtained. Bereaved caregiver depression was assessed 6 months or more after patient death via mail survey using the Patient Health Questionnaire-9 (PHQ-9). A multivariable logistic regression analysis was used to explore variables predicting bereaved caregiver depression. RESULTS: Of 1324 deceased patient-bereaved caregiver dyads, data were finally analyzed for 711 dyads. The proportion of probable depression (PHQ-9 scores ≥10) in bereaved caregivers was 13.6% (91/671; 95% confidence interval: 11.0-16.2). The multivariable logistic regression analysis showed that patient hyperactive delirium at PCU admission was significantly associated with the development of bereaved caregiver depression (odds ratio: 2.2, 95% CI: 1.2-3.8). Bereaved caregiver perceived low social support (OR: 4.7, 95% CI: 2.2-10.0) and low preparedness for death (OR: 4.5, 95% CI: 2.6-7.8) were also significantly associated with the development of depression. Other patient and bereaved caregiver variables had no association with depression. CONCLUSIONS: Hyperactive delirium in terminally ill cancer patients was associated with bereaved caregiver depression. The development of effective strategies to reduce delirium-related agitation and to provide educational interventions for caregivers may be needed.

Association between respiratory and heart rate fluctuations and death occurrence in dying cancer patients: continuous measurement with a non-wearable monitor.

BACKGROUND: The present study aimed to explore the association between impending death and continual changes in respiratory and heart rates measured using a non-wearable monitor every minute for the final 2 weeks of life in dying cancer patients. METHODS: In this longitudinal study, we enrolled patients in a palliative care unit and continuously measured their respiratory and heart rates via a monitor and additionally captured their other vital signs and clinical status from medical records. RESULT: A dataset was created comprising every 24-h data collected from every-minute raw data, including information from 240 days prior to death from 24 patients (345,600 data); each patient's data were measured for 3-14 days until death. After confirming the associations between the respiratory and heat rate values on the day of death (n = 24) or other days (2-14 days before death, n = 216) and the mean, maximum, minimum, and variance of respiratory and heart rates every 24 h by univariate analyses, we conducted a repeated-measures logistic regression analysis using a generalized estimating equation. Finally, the maximum respiratory rate and mean heart rate were significantly associated with death occurring within the following 3 days (0-24 h, 0-48 h, and 0-72 h), except for the maximum respiratory rate that occurs within 0-24 h. CONCLUSION: The maximum respiratory rate and mean heart rate measured every minute using a monitor can warn family caregivers and care staff, with the support of palliative care professionals, of imminent death among dying patients at home or other facilities.

Prevalence of Myofascial Pain Syndrome and Efficacy of Trigger Point Injection in Patients with Incurable Cancer: A Multicenter, Prospective Observational Study (MyCar Study).

OBJECTIVE: Myofascial pain syndrome (MPS) is caused by overload or disuse of skeletal muscles. Patients with cancer are often forced to restrict their movement or posture for several reasons. The study was conducted to investigate the prevalence and risks of MPS in patients with incurable cancer. The efficacy of trigger point injection (TPI) was also explored. METHODS: This was a multicenter, prospective observational study. Patients with incurable cancer who started receiving specialist palliative care were enrolled. We investigated the MPS in this population and accompanying risk factors for restricting body movement. Pre- and post-TPI pain was also evaluated using a Numerical Rating Scale (NRS) in patients who received TPI. The primary outcome was the prevalence of MPS. RESULTS: A total of 101 patients were enrolled from five institutions in Japan. Most of the patients (n = 94, 93.1%) had distant metastases, and half of the patients (50, 49.5%) received anticancer treatment. Thirty-nine (38.6%) patients had MPS lesions at 83 sites. Multivariate analysis revealed that the significant risk factor for MPS was poor Performance Status (PS) (odds ratio 3.26; 95% confidence interval [CI] 1.18-9.02, P = .023). We performed TPI for 40 out of 83 MPS lesions. Mean NRS for MPS before TPI was 7.95, which improved to 4.30 after TPI (P < .001). CONCLUSIONS: MPS was common in patients with incurable cancer and the risk factor identified in this study was poor performance status. TPI could be a treatment option.

Thromboembolism and bleeding in patients with autoimmune blistering disease.

The prevention and early detection of venous thromboembolism (VTE), including pulmonary embolism (PE), is essential in daily medical practice. We previously reported the risk of VTE in patients with autoimmune blistering disease (AIBD). We have also experienced multiple cases of pemphigus or pemphigoid that developed severe complications related to abnormal blood coagulation other than VTE. This study summarizes and discusses those cases. Nine patients with AIBD developed thromboembolism and/or bleeding; these included (some patients overlapped) six patients with VTE, including five patients with PE; three patients with severe bleeding; one patient with sudden critical limb ischaemia resulting in thigh amputation; and one patient with cerebral infarction. Although five patients developed PE, only one had apparent respiratory symptoms with PE, and a second developed severe bleeding during the treatment for PE. Clinicians should be aware of the systemic complications related to abnormal blood coagulation when treating patients with AIBD.

Nonwearable actigraphy to assess changes in motor activity before and after rescue analgesia in terminally ill patients with cancer: A pilot study.

AIMS: This study aimed to investigate the usefulness of nonwearable actigraphy to assess changes in motor activity before and after rescue analgesic administration in terminally ill cancer patients. BACKGROUND: Evaluating pain in terminally ill cancer patients is difficult; pain assessment tools are needed. METHODS: This was an exploratory descriptive study conducted within a palliative care unit. A nonwearable actigraph was used to measure the activity score and movement index of terminally ill patients with weeks-long prognosis and pain. The actigraph and medical data were integrated, and data were compared 6 h before and after rescue analgesic administration. RESULTS: Among 10 patients (age: 75.8 ± 12.3 years; six men), we evaluated 28 pain episodes (mean activity score: 130.9 ± 180.5 counts per minute; movement index: 68.8%). When pain was relieved at night following rescue analgesic administration, activity score and movement index decreased significantly (6 h before vs. 6 h after analgesics, respectively: 113.1 to 69.7 counts per minute; 64.3% to 41.8%; both p < 0.0001). With no relief after rescue analgesic administration, activity score did not differ significantly 6 h before and after analgesics: 147.3 to 137.7 counts per minute. CONCLUSION: Pain in terminally ill cancer patients could be assessed using a nonwearable actigraph to capture motor activity and improve pain assessment.

Effects of parenteral nutrition and hydration on survival in advanced cancer patients with malignant bowel obstruction: secondary analysis of a multicenter prospective cohort study.

PURPOSE: The benefits of parenteral nutrition and hydration (PNH) in patients with advanced cancer remain unknown. Therefore, we conducted a prospective multicenter cohort study to assess the effects of PNH on survival in patients with malignant bowel obstruction (MBO). METHODS: The present study was a secondary analysis. Data on primary nutritional administration routes during the first week of admission to palliative care units, i.e., parenteral nutrition and parenteral hydration, were obtained. Data on the averaged calorie sufficiency rate/total calorie intake (75% ≤ or 750 kcal/day ≤ , 50-75% or 500-750 kcal/day, 25-50% or 250-500 kcal/day, and < 25% or < 250 kcal/day) were also obtained. Participants with MBO were included and divided into two groups: PNH-high (25% ≤ or 250 kcal/day ≤) and PNH-low (< 25% or < 250 kcal/day). We performed time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses. RESULTS: Patients were divided into the PNH-high (n = 68) and PNH-low (n = 76) groups. A significant difference was observed in survival rates between the two groups (log-rank P < 0.001). Median survival times were 35.5 (95% CI 27-44) and 17.5 (95% CI 13-21) days, respectively. In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the PNH-high group (HR 0.55 (95% CI 0.36-0.83), P = 0.005) than in the PNH-low group. CONCLUSION: The present results indicated the beneficial effects of PNH for prolonging survival in advanced cancer patients with MBO in palliative care units.

Psoriasis with short stature improved by adalimumab.

Few cases of pediatric psoriasis with short stature, possibly resulting from chronic systemic inflammation, have been reported. We present the case of a child with short stature occurring after the onset of psoriasis wherein treatment with adalimumab resulted in the improvement of not only the psoriasis but also the child's short stature. Pediatric psoriasis associated with short stature may benefit from the early induction of biologic therapy.

Complexity of desire for hastened death in terminally ill cancer patients: A cluster analysis.

OBJECTIVES: The present study aims were (1) to identify the proportion of terminally ill cancer patients with desire for hastened death (DHD) receiving specialized palliative care, (2) to identify the reasons for DHD, and (3) to classify patients with DHD into some interpretable subgroups. METHODS: Advanced cancer patients admitted to 23 inpatients hospices/palliative care units in 2017 were enrolled. Data were prospectively obtained by the primarily responsible physicians. The presence/absence of DHD and reasons for DHD were recorded. A cluster analysis was performed to identify patterns of subgroups in patients with DHD. RESULTS: Data from 971 patients, whose Richmond Agitation-Sedation Scale score at admission was zero and who died in palliative care units, were analyzed. The average age was 72 years, common primary cancer sites were the gastrointestinal tract (31%) and the liver/biliary ducts/pancreas (19%). A total of 174 patients (18%: 95% confidence interval, 16-20) expressed DHD. Common reasons for DHD were dependency (45%), burden to others (28%), meaninglessness (24%), and inability to engage in pleasant activities (24%). We identified five clusters of patients with DHD: cluster 1 (35%, 61/173): "physical distress," cluster 2 (21%, 37/173): "dependent and burdensome," cluster 3 (19%, 33/173): "hopelessness," cluster 4 (17%, 30/173): "profound fatigue," and cluster 5 (7%, 12/173): "extensive existential suffering." CONCLUSIONS: A considerable number of patients expressed DHD and could be categorized into five subgroups. These findings may contribute to the development of therapeutic strategies.

A Case of Methotrexate-Associated Lymphoproliferative Disorder (Lymphomatoid Granulomatosis) of the Skin.

Iatrogenic lymphoproliferative disorder (LPD) can develop in patients treated with immunosuppressive drugs for autoimmune or other inflammatory diseases. Here, we report a case of lymphomatoid granulomatosis of the skin that occurred as a methotrexate (MTX)-associated LPD. We also review the relevant literature. A 73-year-old woman presented to our department with an approximately 10-year history of MTX therapy for rheumatoid arthritis. Three months earlier, she noticed a small nodule in her right upper arm. It gradually enlarged, and the center began to decay. Grossly, the lesion was 40 × 40 mm in size with ulceration, and the surrounding skin presented dark red erythema. A biopsy specimen was taken for definitive diagnosis. Histologically, infiltrating growth of medium-to-large atypical lymphocytes was observed underneath the ulceration and was accompanied by small reactive lymphocytes. The atypical lymphocytes demonstrated a tendency to infiltrate the vessels, which showed an angiocentric pattern. Immunohistochemistry revealed that the atypical lymphoid cells were positive for CD79a, CD20, and CD30. In addition, in situ hybridization for Epstein-Barr virus (EBV) revealed expression of EBV-encoded small RNAs. The patient was diagnosed with MTX-associated LPD (lymphomatoid granulomatosis), owing to her history of MTX treatment, the expression of the atypical lymphocytes for B-cell markers and EBV-encoded small RNA, and the angiocentric infiltrating pattern. The lesion reportedly disappeared after withdrawal of MTX.

Side effects of corticosteroids in patients with advanced cancer: a systematic review.

PURPOSE: Corticosteroids are commonly used in palliative care settings, but are associated with several side effects. Although adverse events (AEs) are highly distressing for patients, few data are available from prospective studies to look at incidence or predictors of such harms. The aim of this study is to identify AE reporting among studies of patients with advanced cancer receiving corticosteroids for any reason. METHODS: A systematic review was conducted using the following data sources: PubMed, Medline, SCOPUS, Cochrane reviews, and CINAHL. Randomized controlled trials (RCTs) with patients with advanced cancer assessing the effect of corticosteroids were included. Consecutive cohort observational studies of corticosteroid toxicities in cancer patients were also included. RESULTS: Twenty-seven RCTs and 12 consecutive cohort observational studies were identified. The most frequently reported primary outcome of RCTs was nausea and vomiting (8/27). Dexamethasone was prescribed in almost half of RCTs (13/27). In consecutive cohort studies, the primary outcomes were a wide variety of symptoms. Dexamethasone was also the most common glucocorticoid used (7/12). In terms of quality of AE reporting, two RCTs and one consecutive cohort study used a validated AE assessment tool in their studies. CONCLUSIONS: Side effects of corticosteroids in advanced cancer patients were poorly reported with few data using validated tools. Researchers should be aware of the guideline of AE reporting to provide the best evidence of risk-benefit balance. Developing specific consensus guidelines about AE reporting in studies of glucocorticoids in studies of people with advanced cancer would be useful.

Japanese Cancer Survivors' Awareness of and Participation in Support Groups.

Cancer survivors face many challenges, and cancer support groups provide a range of support. Several reports have shown the benefits of support groups. However, it is not clear how Japanese cancer survivors use them. This study aimed to examine cancer survivors' awareness of and reasons for participation or non-participation in cancer support groups. We conducted a cross-sectional questionnaire survey with ambulatory patients with cancer across eight designated cancer hospitals. The questionnaire covered patients' demographics, disease characteristics, participation/non-participation in cancer support groups, and reasons for participation/non-participation. In total, 569 questionnaires were distributed, and responses were received from 275 patients with cancer. Of these, 135 patients were aware of support groups and 23 had participated in a group. Patients who were aware of support groups were more likely to be young, female patients. Many patients learned about support groups from hospital notices. Most support group participants expected to receive information about the disease and treatment (91%). They also wanted to hear about other patients' experiences (73%). The most common reasons for non-participation were "no particular reason" (38%) and "family or friends support me" (27%). About half of participating patients were unaware of support groups. Even among patients who were aware, many did not attend a support group. Developing a better understanding of support group use in cancer survivors may enhance provision of adequate care based on individual needs.

Cochineal dye-induced immediate allergy: Review of Japanese cases and proposed new diagnostic chart.

BACKGROUND: Cochineal dye is used worldwide as a red coloring in foods, drinks, cosmetics, quasi-drugs, and drugs. The main component of the red color is carminic acid (CA). Carmine is an aluminum- or calcium-chelated product of CA. CA and carmine usually contain contaminating proteins, including a 38-kDa protein thought to be the primary allergen. Severe allergic reactions manifest as anaphylaxis. The aim of this study was to review all Japanese reported cases and propose useful diagnostic chart. METHODS: All reported Japanese cases of cochineal dye-induced immediate allergy were reviewed, and newly registered cases were examined by skin prick test (SPT) with cochineal extract (CE) and measurement of CE and carmine-specific serum IgE test. Two-dimensional (2D) western blotting using patient serum was conducted to identify the antigen. RESULTS: Twenty-two Japanese cases have been reported. SPT and the level of specific IgE test indicated that six cases should be newly registered as cochineal dye allergy. All cases were adult females, and all cases except three involved anaphylaxis; 13 cases involved past history of local symptoms associated with cosmetics use. Japanese strawberry juice and fish-meat sausage, and European processed foods (especially macarons made in France) and drinks were recent major sources of allergen. 2D western blotting showed that patient IgE reacted to the 38-kDa protein and other proteins. Serum from healthy controls also weakly reacted with these proteins. CONCLUSIONS: SPT with CE and determination of the level of CE and carmine-specific IgE test are useful methods for the diagnosis of cochineal dye allergy.

Wy14643, an agonist for PPARα, downregulates expression of TARC and RANTES in cultured human keratinocytes.

Beneficial effects of Wy14643, an agonist for peroxisome proliferator-activated receptor (PPAR)α, on permeability barrier homeostasis-related functions of keratinocytes such as up-regulation of epidermal differentiation-related molecules and lipid synthesis, have been demonstrated. The present study demonstrated that Wy14643 reduced the expression of thymus and activation-related chemokine (TARC) and regulated on activation normal T cell expressed (RANTES) in both single- and 3D-cultured human keratinocytes. The combined data of the present and previous studies support the notion that Wy14643 could be a therapeutic agent that might simultaneously and directly modulate permeability barrier dysfunction and allergic inflammation in the pathogenesis of atopic dermatitis. As for the anti-microbial barrier function, the present study demonstrated that Wy14643 up-regulated expression of the anti-microbial peptide, human ß defensin 3, in cultured human keratinocytes only in mRNA levels but not in protein ones, suggesting that Wy14643 might not directly account for the up-regulation of the anti-microbial peptide which has been reported in vivo.

The relationship between cancer patients' place of death and bereaved caregivers' mental health status.

BACKGROUND: Although place of death has been recognized as a risk factor in caregivers' bereavement adjustment, the estimation of the effect of the place of death needs careful consideration about many potential cofounders. PATIENTS AND METHODS: This study was a nationwide cross-sectional questionnaire survey for bereaved family caregivers of patients with cancer who died in 3 settings: (1) hospice at home; (2) palliative care units (PCUs); and (3) acute hospitals. We assessed bereaved caregivers' depression, grief, insomnia, and the quality of dying of deceased patients across the 3 groups using propensity score weighting. RESULTS: A total of 8968 responses were analyzed. According to scores on Patient Health Questionnaire 9, depressive symptoms were significantly higher in bereaved caregivers of patients who had died in acute hospitals (5.7; 95% confidence interval [CI]: 5.3-6.2) than for those of patients who had died in hospice at home (4.8; 95% CI: 4.4-5.1) or PCU (5.1; 95% CI: 5.0-5.2). Grief symptoms measured by Brief Grief Questionnaire were also significantly higher in caregivers of patients who had died in acute hospitals (5.0; 95% CI: 4.8-5.2) than those of patients who had died in hospice at home (4.7; 95% CI: 4.5-4.9) or PCU (4.7; 95% CI: 4.7-4.8). Deceased patients' quality of dying was highest in hospice at home, and worst in acute hospital. CONCLUSIONS: The place where a cancer patient dies influences not only their quality of dying and death but also the mental health of their family caregivers. However, the absolute difference is not large after adjustment of multiple variables.

Toxic epidermal necrolysis in a child 6 months post-hematopoietic stem cell transplantation.

TEN is a rare and critical disease mostly caused by drugs. It is mediated by activated CD8+ T cells that cause keratinocyte apoptosis with the assistance of cytokines/chemokines. We herein report a pediatric case of TEN after allogeneic HSCT with precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) in second complete remission. Although we did not evaluate the T-cell subpopulation in blood or skin lesion of the patient, an imbalanced immune reconstitution after HSCT might additively contribute to the development of TEN.

Caregiver characteristics and bereavement needs: Findings from a population study.

BACKGROUND: Globally, most care for people with life-limiting illnesses is provided by informal caregivers. Identifying characteristics of caregivers that may have unmet needs and negative outcomes can help provide better support to facilitate adjustment. AIM: We compared characteristics, expressed unmet needs and outcomes for spousal caregivers, with other caregivers at the end of life, by gender and age. DESIGN: The South Australian Health Omnibus is an annual, random, face-to-face, cross-sectional survey wherein respondents are asked about end-of-life care. SETTING/PARTICIPANTS: Participants were aged over 15 years, resided in households in South Australia and had someone close to them die from a terminal illness in the last 5 years. RESULTS: Of the 1540 respondents who provided hands-on care for someone close at the end of life, 155 were widows/widowers. Bereaved spousal caregivers were more likely to be older, female, better educated, have lower incomes, less full-time work, English as second language, sought help with grief and provided more day-to-day care for longer periods. Spousal caregivers were less likely to be willing to take on caregiving again, less able to 'move on' with life and needed greater emotional support and information about illness and services. The only difference between widows and widowers was older age of spouse in women. Younger spousal caregivers perceived greater unmet emotional needs and were significantly less likely to be able to 'move on'. CONCLUSION: Spousal caregivers are different from other caregivers, with more intense needs that are not fully met. These have implications for bereavement, health and social services.

Using drawing tests to explore the multidimensional psychological aspects of children with cancer.

In seeking to understand how life-threatening illness affects children psychologically, projective testing may be beneficial, particularly when attempting to identify psychological problems in younger adolescents. The advantages of projective testing are that it does not depend on patients' verbal ability and is not invasive. Three cancer inpatients from Kyoto Prefectural University of Medicine, aged between 10 and 16 years old, participated in the study. Projective testing was used to measure the depth of participants' distress and included a tree-drawing test, a person-drawing test and a free drawing test. Results from the tree- and person-drawing tests indicated energy loss, anxiety and a sense of emptiness. However, results from the free drawing test suggested that the children had hope and a desire to recover from their illness. The combination of drawing tests in this study may increase the understanding of the internal psychological difficulties faced by children hospitalized with cancer.

Intractable Nocardial mycetoma with possible colonisation by Candida species.

A Japanese male in his 30s with no underlying medical condition presented with painless nodules after being bitten by a dog during a stay in Bali, Indonesia, 7 years earlier. He was referred to our department with multiple ulcers, nodules, and masses on the right leg. The final diagnosis was mycetoma caused by Nocardia vulneris, which may have been exacerbated by colonization of Candida parapsilosis and C. tropicalis as these yeasts were isolated by culture from the tissue. Treatment with minocycline hydrochloride and sulfamethoxazole trimethoprim showed partial efficacy, but the addition of posaconazole achieved significant efficacy. This suggests that the surmised coexistence of pathogenic yeasts of lower virulency may have made mycetoma in this case intractable.