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.

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.

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.

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.

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.

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.

Efficacy of pediatric acute pancreatitis scores at a Japanese tertiary center.

BACKGROUND: Pediatric acute pancreatitis (AP) is a rare but important clinical entity associated with significant morbidity. Predicting the severity and outcome of AP in pediatric patients can be challenging because there are few validated severity scoring systems. Moreover, the etiology of pediatric AP in the Japanese population is different from that of Western populations. The performance of severity scores in pediatric AP with a high prevalence of severe cases is still unknown. The aim of this study was to assess the performance of existing severity scoring systems when used for Japanese children at a tertiary care center. METHODS: We reviewed the electronic medical records of all children (≤18 years) treated for AP at between 2002 and 2012 at National Center for Child Health and Development, Tokyo. The modified Glasgow acute pancreatitis severity score (modified Glasgow), Ranson criteria (Ranson), Balthazar computed tomography severity index (CTSI), and pediatric acute pancreatitis severity (PAPS) score were assessed for their ability to distinguish severe pancreatitis from the milder forms. RESULTS: Thirty-three Japanese children with AP were identified. Among them, 37 episodes were analyzed for the performance of the scoring systems and 33 for the etiology. The most common etiology of AP was structural abnormality (n = 8). Sensitivity for the modified Glasgow, Ranson, PAPS, and CTSI was 42.9%, 52.4%, 81.0%, and 50.0%, respectively, while specificity was 81.3%, 81.3%, 37.5%, and 76.9%, respectively. CONCLUSION: We found PAPS to be the most reliable when used for discriminating the severe form of AP from the milder forms at a Japanese tertiary pediatric care center.

The developmental characteristics of locomotion and sleep in cyclic vomiting syndrome and the effects of drug therapy.

Objective: To evaluate the characteristics of patients with cyclic vomiting syndrome (CVS) and the efficacy of prophylaxis therapy. Methods: We defined the patients as "CV (+) " if they had multiple neuromuscular diseases and as "CV (−) " if they did not. We compared the two groups according to their background and the type of medications and their effects. We also evaluated their locomotion and sleep pattern. Results: There was no significant difference between CV (+) and CV (−) with regard to the association with migraine. Pharmacotherapy with cyproheptadine and valproate had high success rate for both CV (−) and CV (+). The rate of delayed locomotion development and atonia during non-REM sleep was high in both CV (+) and CV (−). Conclusions: We postulate that the association of serotonergic neurons is one of the important factors in both CV (+) and CV (−).

[Advance Care Planning in Cancer Care].

Advance care planning (ACP) is one of the most important issues to consider in providing quality end of life care for cancer patients. ACP has been described as a process whereby a patient, in consultation with health care providers, family members, and important others, makes decisions about his or her future health care, in the event he or she becomes incapable of participating in medical treatment decisions. ACP improves rates of following end of life wishes, increases patient and family satisfaction, and reduces family stress, anxiety, and depression. This article clarifies the differences among ACP, advance directives, and living wills. Additionally, we describe, based on clinical experience, how to introduce ACP most effectively for all stages of cancer care.

Factor-associated caregiver burden in medically complex patients with special health-care needs.

BACKGROUND: Many medically complex patients with special health-care needs (PSHCN) receive home-based medical support, placing a major burden on their caregivers. We characterized the caregiving factors involved in PSHCN and their relationship with caregiver burden. METHODS: The PSHCN and their families were recruited from children's hospitals and rehabilitation centers. A medical information handbook was distributed to the families on enrollment, followed by a self-report questionnaire 1 year later. Data on the type of caregiving involved, family circumstances, and caregiver burden were collected. The Zarit caregiver burden scale (ZS) was used to evaluate caregiver burden. Logistic regression (proportional odds model) was used to determine associations between each variable and caregiver burden in each of two PSHCN age groups: <15 years old (younger group) and ≥ 15 years (older group). RESULTS: Sixty-eight PSHCN and their families were included in the analysis. The mean age of the PSHCN was 15.4 ± 11.8 years. On multivariate analysis there was a significant positive correlation between ZS score and older siblings (odds ratio [OR], 3.65), but no significant correlation between caregiver burden and type of care involved in the younger group. In the older group, a positive correlation was observed between caregiver burden and home mechanical ventilation with tracheostomy (OR, 15.16), but a negative correlation with younger siblings (OR, 0.04). CONCLUSIONS: Family circumstances play a bigger role than type of care required in increasing caregiver burden in families of PSHCN aged less than 15 years.

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.

Children with medical complexity receiving home healthcare devices in Japan: a retrospective cohort study.

BACKGROUND: Limited evidence exists regarding children receiving home healthcare devices (HHDs). This study aimed to describe the range and type of HHD use by children with chronic medical conditions in Japan and explore factors leading to increased use of these devices. METHODS: This retrospective cohort study was conducted using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Children receiving HHD aged ≤18 years between April 2011 and March 2019 were included. Children newly administered HHD between 2011 and 2013 were followed up for 5 years, and logistic regression analysis was performed to assess the relationship between increased HHD use and each selected risk factor (comorbidity or types of HHD). The models were adjusted for age category at home device introduction, sex and region. RESULTS: Overall, 52 375 children receiving HHD were identified. The number (proportion) of children receiving HHD increased during the study period (11 556 [0.05%] in 2010 and 25 593 [0.13%] in 2018). The most commonly administered HHD was oxygen (51.0% in 2018). Among the 12 205 children receiving HHD followed up for 5 years, 70.4% and 68.3% who used oxygen or continuous positive airway pressure, respectively, were released from the devices, while only 25.8% who used mechanical ventilation were released from the device. The following diagnosis/comorbidities were associated with increased HHD use: other neurological diseases (OR): 2.85, 95% CI): 2.54-3.19), cerebral palsy (OR: 2.16, 95% CI: 1.87 to 2.49), congenital malformations of the nervous system (OR: 1.70, 95% CI: 1.34 to 2.13) and low birth weight (OR: 1.68, 95% CI: 1.41 to 2.00). CONCLUSIONS: This study provides nationwide population-based empirical data to clarify the detailed information regarding children receiving HHD in Japan. This information could assist healthcare professionals in improving the quality of life of these children and their families and help health policymakers consider measures.

The value of radiographic findings for the progression of pandemic 2009 influenza A/H1N1 virus infection.

BACKGROUND: Most illnesses caused by pandemic influenza A (H1N1) pdm09 virus (A/H1N1) infection are acute and self-limiting among children. However, in some children, disease progression is rapid and may require hospitalization and transfer to a pediatric intensive care unit (PICU). We investigated factors associated with rapid disease progression among children admitted to hospital for A/H1N1 infection, particularly findings on initial chest radiographs. METHODS: In this retrospective study, we investigated the records of children who had received a laboratory or clinical diagnosis of A/H1N1 infection and were admitted to the largest children's hospital in Japan between May 2009 and March 2010. The medical records were reviewed for age, underlying diseases, vital signs on admission, initial chest radiographic findings, and clinical outcomes. According to chest radiographic findings, patients were classified into 4 groups, as follows: [1] normal (n = 46), [2] hilar and/or peribronchial markings alone (n = 64), [3] consolidation (n = 64), and [4] other findings (n = 29). Factors associated with clinical outcomes were analyzed using logistic regression. RESULTS: Two hundreds and three patients (median 6.8 years) were enrolled in this study. Fifteen percent (31/203) of patients were admitted to PICU. Among 31 patients, 39% (12/31) of patients required mechanical ventilation (MV). When the initial chest radiographic findings were compared between patients with consolidation (n = 64) and those without consolidation (n = 139), a higher percentage of patients with consolidation were admitted to PICU (29.7% vs.8.6%, P < 0.001) and required MV (17.2% vs. 0.7%, P < 0.001). These findings remain significant when the data were analyzed with the logistic regression (P < 0.001, P < 0.001, respectively). CONCLUSIONS: Consolidation on initial chest radiographs was the most significant factor to predict clinical course of hospitalized children with the 2009 A/H1N1 infection.

[Anaphylaxis and biphasic reaction in a children hospital].

BACKGROUND AND AIMS: Anaphylaxis is an acute multi-systemic and potentially fatal reaction, resulting from the exposure to antigens. There are few detailed reports of children with anaphylaxis. We studied the actual condition of an anaphylaxis including biphasic reaction. METHODS: This is a retrospective case study of children presenting to the Emergency Department of the National Center for Child Health and Development with anaphylaxis between 2002 and 2010. Etiology, age, sex ratio, clinical features, and management were examined. RESULTS: The median age of the patients was 36 months. Boys were predominant (63%). Seven cases developed anaphylactic shock, but all survived. As causes of anaphylaxis, food was identified in 85% of the patients, including eggs, dairy products and nuts, and drugs were identified in 3% of the patients. Initial symptoms consisted of mucocutaneous lesions (90%) and respiratory symptoms (71%). Epinephrine was given in 75 patients (22%). The biphasic anaphylactic reaction was observed in 3 out of the 340 cases (0.9%). In age, sex, grade and symptoms, there was no significant difference between patients with biphasic anaphylactic reaction and monophasic reaction. CONCLUSION: We clarified that the incidence of biphasic anaphylactic reaction was 0.9% in pediatric patients for the first time in Japan.

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.

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.

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.