Current status of pediatric palliative care and decision making in Japan.

Specialized pediatric palliative care (PPC) in Japan evolved primarily to care for children with cancer. As a result, the system for providing PPC to pediatric cancer patients is much more advanced than systems for non-cancer patients with life-limiting diseases. About 40% of pediatric cancer patients die at home, while most non-cancer patients die in the hospital under intensive care. In Japan, the wishes of the family tend to precede the children in decision-making for children who lack decision-making capacity. This is true even for adolescents whose medical treatment decisions may not fully reflect the wishes and preferences of the teen patients. There are efforts to empower adolescents to participate in shared decision making.

The effect of palliative care team intervention and symptom improvement using patient-reported outcomes: a multicenter prospective observational study.

PURPOSE: Hospital-based palliative care teams (HPCTs) are widespread internationally, but multicenter studies about their effectiveness, using patient-reported outcomes (PROs), are limited to Australia and a few other countries. We conducted a multicenter, prospective observational study in Japan to explore the effectiveness of the HPCTs using PROs. METHODS: Nationwide, eight hospitals participated in the study. We included newly referred patients for one month in 2021 and followed them for one month. We asked the patients to complete the Integrated Palliative Care Outcome Scale or the Edmonton Symptom Assessment System as PROs at the time of the intervention, three days later, and weekly after the intervention. RESULTS: A total of 318 participants were enrolled, of whom 86% were patients with cancer, 56% were undergoing cancer treatment, and 20% received the Best Supportive Care. After one week, the following 12 symptoms showed more than a 60% improvement from severe to moderate or less: vomiting (100%), shortness of breath (86%), nausea (83%), practical problems (80%), drowsiness (76%), pain (72%), poor sharing of feelings with family or friends (72%), weakness (71%), constipation (69%), not feeling at peace (64%), lack of information (63%), and sore or dry mouth (61%). Symptoms with improvement from severe/moderate to mild or less were vomiting (71%) and practical problems (68%). CONCLUSION: This multicenter study showed that HPCTs effectively improved symptoms in several severe conditions, as assessed by PROs. This study also demonstrated the difficulty of relieving symptoms in patients in palliative care and the need for improved care.

Necrotizing fasciitis following rapidly deteriorating neonatal omphalitis with good initial presentation.

Neonatal omphalitis is a postpartum infection of periumbilical superficial soft tissues that usually has a good prognosis in developed countries. In rare cases, it could progress to periumbilical necrotizing fasciitis (NF), which is an infection of the deep soft tissues, including muscle fascia, and has a high mortality rate. However, the signs and timing of developing NF secondary to omphalitis are unclear. We encountered a neonatal case of NF following omphalitis. In the initial days of the clinical course, general symptoms and condition of the patient were good, and abdominal physical findings were mild; however, the patient rapidly developed NF. The patient was successfully treated by emergent surgical debridement, broad-spectrum antibiotics, and intensive care. To determine the area of blood perfusion, we intravenously injected indocyanine green by intraoperative angiography, and then extensively removed necrotic and hypoperfused tissues. In neonatal omphalitis, the deterioration can suddenly occur despite good initial conditions; intensive monitoring should be required during the first few days of the clinical course.

A Neonate with Mucopolysaccharidosis Type VII with Intractable Ascites.

We report a case of a patient with severe fetal hydrops and refractory ascites, diagnosed as mucopolysaccharidosis type VII (MPS VII) by whole-exome sequencing, and discharged at 5 months of age after long-term ventilatory management. A male neonate was born by emergency cesarean section due to fetal distress at 30 1/7 weeks' gestation. Physical examination and X-rays revealed pleural effusion, ascites, and generalized edema, indicating severe fetal hydrops. He underwent tracheal intubation because of respiratory distress that was attributed to massive ascites, pulmonary hypoplasia, and pulmonary hypertension. He received mechanical ventilation and inhaled nitric oxide therapy. Prednisone, octreotide, and a factor XIII preparation were used as the treatment for ascites, and the ascites gradually decreased. He was extubated within 2 months of age. At 4 months of age, the results of whole-exome sequencing of the cord blood showed a compound heterozygous mutation in the GUSB gene, the gene responsible for MPS VII. Enzyme replacement therapy was initiated, and the ascites was resolved. Careful systemic management, including lung-protective respiratory management and the early establishment of nutrition, is important for the long-term survival of infants with fetal hydrops, and early aggressive workup, including whole-genome sequencing for the cause, should be performed in the case of refractory ascites.

Nurses' perception of pediatric pain and pain assessment in the Japanese PICU.

BACKGROUND: Nurses play an essential role in pain management in the pediatric intensive care unit (PICU). However, their perceptions regarding pediatric pain and current practice of pain assessment in Japanese PICUs remain unknown. METHODS: In January 2021, we conducted a multicenter, cross-sectional survey across 35 PICUs in Japan. A structured questionnaire which focused on nurses' perceptions of pediatric pain and pain assessment was developed, pilot-tested, and revised. Twenty copies of the questionnaire were sent to each institution and were distributed to the nursing staff. RESULTS: A total of 356 nurses from 22 institutions responded. Median age of the respondents was 33 years and 84.6% were female. Median length of nursing experience and PICU experience were 10 and 4 years, respectively. Use of pain scales for assessing pain in children who can self-report pain, preverbal children, and children unable to self-report pain due to cognitive impairment were 90.7%, 55.9%, and 50.0%, respectively. Nurses' satisfaction regarding pain management in their PICU was 31.9% and their confidence in pain assessment and management were 32.6% and 44.9%, respectively. Lack of knowledge (95.8%), difficulty assessing pain in children (95.2%), and delay in physician's action (91.8%) were the most perceived barriers to optimal pain management. CONCLUSIONS: The use of pain scales is insufficient and nurses' satisfaction proved to be extremely low in the Japanese PICUs. Substantial effort is required to enhance the level of current pain management and improve outcomes.

Factors associated with high care burden of primary caregivers of children with medical complexity after completing a discharge-support program in a recovery center.

INTRODUCTION: Recently, many seriously ill children requiring medical equipment are being recommended to transition from hospital to home care in Japan. Since 2011, our recovery center has provided a support program for the transfer process from hospital to home for ill children and their families. The purpose of this study was to evaluate the factors related to high care burden after completing the discharge-support program. METHODS: A questionnaire-based cross-sectional study was conducted on all primary caregivers whose children received the program in our center and moved from hospital to home (30 children and 29 families) from May 2011 to May 2018. Fifteen children came from the neonatal intensive care unit. The questionnaire consisted of three parts: characteristics of children and families and life after the program; the Zarit Burden Interview (ZBI); and the Positive and Negative Affect Schedule (PANAS). RESULTS: Twenty-three primary caregivers responded (79% response rate). All children received tracheostomy and 71% received home mechanical ventilation. Primary caregivers were all mothers. High ZBI score was not related to the severity and type of medical equipment. There were relationships between high ZBI score and following factors: 'unimproved relationship between patients and family members without primary caregivers' and 'additional medical equipment after discharge'. The result of PANAS showed that positive attitude was not different between those with high and low ZBI scores. CONCLUSION: It is crucial to reach out to family members without a primary caregiver. Additional medical care/equipment after the program is related to the care burden of primary caregivers.

Current status of intensive end-of-life care in children with hematologic malignancy: a population-based study.

BACKGROUND: Adult patients with hematologic malignancies are less likely to receive palliative care and more likely to accept intensive anti-cancer treatments until end-of-life than those with solid tumors, but limited data are available regarding the quality of end-of-life care (EOLC) for children with hematologic malignancies. To improve the quality of EOLC for children with hematologic malignancies, the aims of this study were (i) to compare intensive EOLC between children with hematologic malignancies and those with solid tumors; and (ii) to describe factors associated with intensive EOLC in children with hematologic malignancies. METHODS: We retrospectively reviewed 0- to 18-year-old patients with cancer, who died in hospital between April 2012 and March 2016 in Japan using the Diagnosis Procedure Combination per-diem payment system. Indicators of intensive inpatient EOLC were defined as intensive care unit admission, cardiopulmonary resuscitation (CPR), intubation and/or mechanical ventilation, hemodialysis, or extra-corporeal membrane oxygenation in the last 30 days of life, or intravenous chemotherapy in the last 14 days. We determined factors associated with intensive EOLC using regression models. Data regarding use of blood transfusion were also obtained from the database. RESULTS: Among 1199 patients, 433 (36%) had hematological malignancies. Children with hematologic malignancies were significantly more likely than those with solid tumors to have intubation and/or mechanical ventilation (37.9% vs. 23.5%), intensive care unit admission (21.9% vs. 7.2%), CPR (14.5% vs. 7.7%), hemodialysis (13.2% vs. 3.1%) or extra-corporeal membrane oxygenation (2.5% vs. 0.4%) in their last 30 days, or intravenous chemotherapy (47.8% vs. 18.4%; all P < .01) within their last 14 days of life. Over 90% of children with hematological malignancies received a blood transfusion within the last 7 days of life. For hematological malignancies, age under 5 years was associated with CPR and ≥ 2 intensive EOLC indicators. Longer hospital stays had decreased odds of ≥ 2 intensive EOLC indicators. CONCLUSION: Children with hematologic malignancies are more likely to receive intensive EOLC compared to those with solid tumors. A younger age and shorter hospital stay might be associated with intensive EOLC in children with hematologic malignancies.

Severe Liver Disorder Following Liver Transplantation in STING-Associated Vasculopathy with Onset in Infancy.

PURPOSE: STING-associated vasculopathy with onset in infancy (SAVI) is a type-I interferonopathy, characterized by systemic inflammation, peripheral vascular inflammation, and pulmonary manifestations. There are three reports of SAVI patients developing liver disease, but no report of a SAVI patient requiring liver transplantation. Therefore, the relevance of liver inflammation is unclear in SAVI. We report a SAVI patient who developed severe liver disorder following liver transplantation. METHODS: SAVI was diagnosed in a 4-year-old girl based on genetic analysis by whole-exome sequencing. We demonstrated clinical features, laboratory findings, and pathological examination of her original and transplanted livers. RESULTS: At 2 months of age, she developed bronchitis showing resistance to bronchodilators and antibiotics. At 10 months of age, she developed liver dysfunction with atypical cholangitis, which required liver transplantation at 1 year of age. At 2 years of age, multiple biliary cysts developed in the transplanted liver. At 3.9 years of age, SAVI was diagnosed by whole-exome sequencing. Inflammatory cells from the liver invaded the stomach wall directly, leading to fatal gastrointestinal bleeding unexpectedly at 4.6 years of age. In pathological findings, there were no typical findings of liver abscess, vasculitis, or graft rejection, but biliary cysts and infiltration of inflammatory cells, including plasmacytes around the bile duct area, in the transplanted liver were noted, which were findings similar to those of her original liver. CONCLUSION: Although further studies to clarify the mechanisms of the various liver disorders described in SAVI patients are needed, inflammatory liver manifestations may be amplified in the context of SAVI.

A Case Report of Bacterial Meningitis Caused by an Emerging Strain of Penicillin-Resistant Non-Vaccine Serotype 10A.

The pneumococcal conjugate vaccines successfully decreased the incidence of invasive pneumococcal diseases and pneumococcal antibiotic resistance. However, they also led to serotype replacements. According to a report by the National Institute of Infectious Diseases (NIID) in 2017, 96% of pneumococcal isolates obtained from children with IPD aged < 5 years were non-PCV13 serotypes. Here, we report the case of a Japanese immunocompetent and vaccinated child who developed refractory meningitis caused by Streptococcus pneumoniae nonvaccine serotype 10A. PCR revealed genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) with triple mutations (pbp1a + 2b + 2x). Multilocus sequence typing identified the strain as a sequence type (ST) 11189. The ST11189 strain has not been reported in Japan, but it has recently been reported as a cause of invasive infections in Korea. The clinical course was complicated by the development of brain and subdural abscesses that necessitated prolonged antibiotic treatment and multiple burr hole drainages. Unfortunately, the neurological sequelae persisted. Continued molecular surveillance is needed for monitoring emerging virulent clinical strains.

Using the upper buttocks as a subcutaneous site for treprostinil infusion in children with pulmonary artery hypertension.

A 14-year-old boy was receiving subcutaneous infusions of treprostinil for pulmonary artery hypertension. Because he had severe infusion site pain in the lower abdomen, we changed his infusion site to the upper buttocks, adding some analgesics. His pain improved gradually. This change may be an effective method for reducing infusion site pain in subcutaneous treprostinil therapy, particularly in children.

A case of neonatal cytomegalovirus infection with severe thrombocytopenia that was successfully managed with empiric antiviral therapy.

Antiviral therapy against cytomegalovirus (CMV) infection is indicated for symptomatic infection in the fetus and premature neonates. In mature neonates, the benefit of antiviral therapy for severe CMV infection remains controversial. Additionally, when diagnosing symptomatic CMV disease occurring during the early neonatal period, it is difficult to differentiate between congenital and acquired infections. We herein report a neonatal case of CMV infection complicated with severe thrombocytopenia that was successfully managed with antiviral treatment. A 21-day-old male infant presented with low-grade fever and erythema on his extremities. During outpatient follow-up, he developed petechiae and thrombocytopenia (platelet count 17,000/µL). Subsequent serological examination and molecular detection of CMV confirmed the diagnosis of CMV infection. In consideration of the severe thrombocytopenia, antiviral therapy with valganciclovir 32 mg/kg/day was initiated. The platelet counts increased with decreasing CMV loads. After excluding congenital CMV infection, we discontinued antiviral therapy without relapse of the disease. The present case suggests that neonatal cases of severe symptomatic CMV infection may require antiviral therapy while excluding the possibility of congenital infection.

Development of a Proxy Quality-of-Life Rating Scale for the End-of-Life Care of Pediatric Cancer Patients Evaluated from a Nurse's Perspective.

Background: Assessing the quality of life (QoL) of children receiving end-of-life (EoL) care through evaluations by the children and their bereaved families is challenging; presently, there is no QoL assessment measure that is appropriate for use in pediatric EoL and/or palliative care. Objective: To develop and test a proxy rating scale (the "Good Death Inventory for Pediatrics," GDI-P) for the QoL of pediatric cancer patients receiving EoL care, evaluated from the nurse's perspective, as well as a short version of the scale. Design, Setting, and Measurements: The GDI-P was developed based on previous studies. After initial testing, it was distributed to hospitals across Japan, where nurses in charge of patients with childhood cancer receiving EoL care used the scale to evaluate a patient retrospectively. To examine inter-rater reliability, we encouraged two nurses to evaluate one patient. The GDI-P was modified on the basis of the responses, and the validity and reliability were measured. Results: In total, 85 questionnaires were completed, including 32 pairs of responses from two nurses evaluating one patient. In addition, 47 retest questionnaires were returned. The final, modified GDI-P comprised eight factors with 22 items and showed high convergent and discriminant validity, scaling success rates for each item and factor, and Cronbach's α values. A short version of GDI-P was prepared, comprising eight representative items. Conclusions: The final GDI-P was confirmed to have adequate reliability and validity. The QoL scale developed in this study should provide useful outcome evaluation criteria for assessing the EoL care of pediatric cancer patients.

Withholding and withdrawal of life-sustaining treatments for neonate in Japan: Are hospital practices associated with physicians' beliefs, practices, or perceived barriers?

OBJECTIVE: To describe the current status of withholding or withdrawal of life-sustaining interventions (LSI) for neonates in Japan and to identify physician- and institutional-related factors that may affect advance care planning (ACP) practices with parents. STUDY DESIGN: A self-reported questionnaire was administered to assess frequency of withholding and withdrawing intensive care at the respondent's facility, the physician's degree of affirming various beliefs about end-of-life care that was compared to 7 European countries, their self-reported ACP practices and perceived barriers to ACP. Three neonatologists at all 298 facilities accredited by the Japan Society for Neonatal Health and Development were surveyed, with 572 neonatologists at 217 facilities responding. RESULTS: At 76% of facilities, withdrawing intensive care treatments was "never" done, while withholding intensive care had been done "sometimes" or more frequently at 82% of facilities. Japanese neonatologists differed from European neonatologists regarding their degree of affirmation of 3 out of 7 queried beliefs about end-of-life care. In hospitals that were more likely to "sometimes" (or more often) withdraw treatments, respondents were less likely to affirm beliefs about doing "everything possible" or providing the "maximum of intensive care". Self-reported ACP practices did not vary between neonatologists based on their hospital's overall pattern of withholding or withdrawing treatments. CONCLUSION: Among NICU facilities in Japan, 21% had been sometimes withdrawing LSI and 82% had been "sometimes" withholding LSI. Institutional treatment practices may have a strong association with physicians' beliefs that then affect end-of-life discussions, but not with self-reported ACP practices.

Number of Unused Medications at the Time of Last Admission: A Prospective Observational Study in a Single Palliative Care Unit.

BACKGROUND:: Unused medications (UM) are an important issue, with the waste associated with UM a burden to the health-care system. The aims of this study were to clarify the amount and costs of UM in patients with advanced cancer at the time of their last admission to a palliative care unit and to explore the factors contributing to the cost of UM and how patients dealt with UM. METHODS:: A prospective observational study was conducted in single palliative care unit. Unused medications were classified into 6 categories and the number and cost of UM by category calculated per patient. Patients were classified into 2 cost groups (high and low) based on the total cost of UM, and the number and cost of UM by category were compared between these 2 groups. RESULTS:: Of 194 consecutive hospitalized patients, data were analyzed for 90. The mean number and cost of UM per patient was 440 and US$301, respectively. Opioids accounted for 47% of the cost of UM. Comparing costs by UM category, the proportion of opioids (51% vs 21%; P < .0001) and oral anticancer drugs (14% vs 3%; P = .02) was higher in the high- than in the low-cost group. CONCLUSION:: Based on the results of the present study, the estimated annual waste cost of UM for patients with cancer who died in Japan was approximately US$110 million. Interventions to educate patients regarding UM and to eliminate barriers to opioid use may help reduce the cost of UM, particularly opioids and anticancer drugs.

Specialist Palliative Care Service for Children With Life-Threatening Conditions: A Nationwide Survey of Availability and Utilization.

CONTEXT: According to the International Observatory on End of Life Care, the level of pediatric palliative care in Japan is Level 2 (capacity building) and the current status of palliative care for children in Japan has not been clarified. OBJECTIVES: The objective of the study was to clarify the availability and utilization of specialist palliative care services among children with life-threatening conditions in Japan. METHODS: A questionnaire was administered to assess the availability of specialist palliative care services among children with life-threatening conditions. All 427 certified regional cancer centers having hospital-based adult palliative care teams, 15 certified children's cancer centers having pediatric palliative care teams, and 368 medical institutions having a certified palliative care unit were surveyed. RESULTS: Fifteen to twenty-one percent of adult palliative care teams and more than 90% of pediatric palliative care teams had experience providing palliative care to children with cancer. By contrast, only 2%-3% of adult palliative care teams and 15% of pediatric palliative care teams had experience providing care for the noncancer population. An estimated 12% of children with cancer in Japan used hospital-based palliative care teams in 2015. Eight children used a palliative care unit in 2015, and of those, seven (88%) had a solid tumor. An estimated 1.3% of children with cancer who died in Japan used a palliative care unit. CONCLUSION: An estimated 12% of children with cancer in Japan used hospital-based palliative care teams and an estimated 1.3% of children with cancer who died in Japan used a palliative care unit in 2015.

Three years' experience with the first pediatric hospice in Asia.

OBJECTIVE: Pediatric hospice has been the adoption of several service provision models in highly developed countries such as UK, Germany, Australia or Canada for a few decades, yet it has seldom been the case in the Asian Continent. This study aimed to evaluate the newest challenge for the children with Life-threatening illness (LTI) and described the characteristic of pediatric palliative care at the first pediatric hospice in Japan. METHODS: A retrospective review of all patients at our pediatric hospice in these three years was conducted. Of the 294 cases reviewed, 269 cases were eligible for analysis. RESULTS: We reviewed 269 patients admitted during the first three years. Most patients required intensive medical intervention. Patients were hospitalized in our pediatric hospice not only for end-of-life care (EOL), but also for respite care. Only 7% of the patients were with cancer. To support children and family to make the most of their time together, we provided a range of medical and recreational care. It is expected that the pediatric hospice will extend and establish cooperation with other hospitals or community services. CONCLUSION: Three years' experience of pediatric palliative care at the first pediatric hospice in the Asian Continent is encouraging. Further experience and improved communication with other pediatric service providers as well as their education in palliative care will enhance the recognition of the capacity of our hospice and support the needs of more children. Furthermore, we would like to introduce the idea of pediatric hospice and spread it throughout the Asian Continent in the future.

Differences between Pediatricians and Internists in Advance Care Planning for Adolescents with Cancer.

OBJECTIVE: To evaluate differences between pediatricians and internists in the practice of and barriers to advance care planning (ACP) for adolescent patients with cancer. STUDY DESIGN: A self-reported questionnaire was administered to assess the practice of ACP, advance directives, and barriers to ACP for adolescent patients with cancer. All 3392 Japanese board-certified hematologists were surveyed, and 600 hematologists (227 pediatricians, 373 internists) who take care of adolescent patients with cancer with decision-making capacity were analyzed. RESULTS: If a patient's prognosis for survival was <3 months, pediatricians were significantly less likely to discuss ACP with their patients than internists, including discussions regarding the patient's medical condition (59% vs 70%), the patient's understanding of his/her medical condition (55% vs 66%), do not attempt resuscitation orders (17% vs 24%), and ventilator treatment if the patient's condition worsened (19% vs 25%). More than 75% of hematologists (both pediatricians and internists) discussed all ACP topics with patients' families. Similarly, with regard to advance directives, pediatricians were less likely than internists to discuss cardiopulmonary resuscitation (24% vs 47%) and the use of ventilators (31% vs 51%), vasopressors (24% vs 42%), and antibiotics (21% vs 31%) with their patients. Both pediatricians and internists discussed these issues more often with patients' families than with patients, especially cardiopulmonary resuscitation (98%) as well as the use of ventilators (98%) and vasopressors (91%). CONCLUSIONS: Pediatricians were less likely than internists to discuss ACP and advance directives with patients, and both pediatricians and internists tended to discuss ACP and advance directives more often with patients' families.