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Objective: To clarify the knowledge and practical skills needed for cancer pain management among nurses on remote islands in Japan and related factors nationwide., Setting: Due to geographical factors, nurses working on remote islands in Japan have few opportunities to attend training programs, which makes it difficult to acquire the knowledge and practical skills needed to provide pain management for patients with cancer., Methods: We conducted a self-administered questionnaire survey regarding knowledge and practical skills in pain management for patients with cancer., Design: Cross-sectional study., Participants: Nurses working in cancer pain care in medical facilities and home care on remote islands throughout Japan., Results: We analysed 128 responses. Regarding knowledge, the average accuracy level was 49.1%. Items with a low accuracy rate included selecting medicine according to the type of pain and the patient's condition. Regarding practice, the items with low scores included analgesics appropriate for the type of pain and relating physical pain to mental, social and spiritual aspects. The most common significant factor in both knowledge and practice was related to postgraduate training., Conclusions: These findings suggest that to improve the knowledge and practical skills for cancer pain management among nurses on remote islands in Japan, it is necessary to incorporate clinical reasoning into basic education and establish remote education systems and consultation systems with other facilities., (© 2024 The Author(s). Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

Background: Although it is known that resilience is negatively associated with burnout, and that certain interventions can effectively increase resilience, little is known about online resilience-enhancing interventions during the COVID-19 crisis. The aim of this study was to identify the association between an online resilience-enhancing intervention and workplace social support, and burnout among nurses working in the mainland and remote islands of Japan during the COVID-19 crisis., Methods: Pretest-posttest was conducted between April 2020 and February 2021, and the questionnaire survey included the bidimensional resilience scale, the Japanese version of Pine's Burnout Measure, and the workplace social support scale. Changes in burnout, resilience, and social support and the associations with nursing discussions as intervention were analyzed. Participants were 98 Nurses with 1 to 10 years of experience from Japan's mainland and remote island hospitals of Kagoshima Prefecture participated in a baseline survey in April 2020. Of these, 76 participated in a secondary survey in September 2020, and 69 participated in the intervention program and a third survey in February 2021. The online intervention over Zoom consisted of small-group nursing discussions based on the broaden-and-build theory., Results: Changes in burnout showed a significant negative association with change in workplace social support (Coef. = -0.019, 95% CI -0.035- -0.003), as did the interaction between change in acquired resilience and intervention (Coef. = -0.088, 95% CI -0.164- -0.011)., Conclusion: Change in workplace social support was significantly negatively associated with changes in burnout, as was the interaction of intervention and acquired resilience. Promotion of this intervention and making workplace social support more accessible may contribute to reduce burnout in nurses., Competing Interests: The authors declare no conflict of interest., (©2023 Tottori University Medical Press.)

Background: Burnout, due to extreme mental and physical fatigue, and emotional exhaustion, leads to decreased nursing quality and turnover. However, not all nurses are observed as burnouts in the same work environment, and resilience and related factors may have effects on the development of burnouts. Therefore, we conducted a cross-sectional study to examine the effects of resilience and related factors on the burnout in clinical nurses, Kagoshima, Japan., Methods: Data for this cross-sectional study involving nurses ( n = 98) was collected using the following questionnaire surveys: the Bidimensional Resilience Scale, The Workplace Social Support Scale, and the Japanese version of the Pine's Burnout Scale. Using burnout as a dependent variable, analyses were conducted using one-way analysis of variance and multiple regression analysis after adjusted for related factors., Results: The prevalence of burnouts was 19.6% on the mainland and 36.1% on remote island. Innate resilience, acquired resilience, workplace social support, and burnout showed no significant difference between nurses on the mainland and remote island. In the mainland participants, innate resilience (β = -0.492, P < 0.001) and acquired resilience (β = -0.325, P = 0.007) showed a negative association with burnout, and similar associations were observed innate resilience (β = -0.520, P = 0.004) and acquired resilience (β = -0.336, P = 0.057) in the remote island participants. For all participants, innate resilience (β = -0.443, P = 0.001) and workplace social support (β = -0.204, P = 0.031) showed a negative association with burnout, and turnover intention was positively associated (β = 0.025, P = 0.021)., Conclusion: A negative association between burnout and innate resilience factors was observed in the mainland and remote island. Further evaluation of innate resilience is necessary for burnout prevention in clinical nurses., Competing Interests: The authors declare no conflict of interest., (©2022 Tottori University Medical Press.)

Background: Food preferences and oral health of older adults greatly affect their nutritional intake, and old-age-related increase in food neophobia may consequently reduce food intake in older adults. This study aimed to determine the impact of food neophobia and oral health on nutritional risk in community-dwelling older adults., Methods: This cross-sectional study included 238 independent adults aged ≥ 65 years (mean, 76.3 ± 7.3 years). The survey items included a Food Neophobia Scale, frequency of protein intake, oral-health-related quality of life (QOL) assessment, and oral diadochokinesis (ODK; /pa/, /ta/, /ka/) as an index of oral function. Nutritional status was assessed using the Mini Nutritional Assessment®, and based on a cutoff value of 24 points, respondents were categorized as well-nourished (≥ 24 points, Group 1) or at risk of malnutrition (< 24 points, Group 2). A logistic regression model was used to calculate the adjusted odds ratio (adj-OR) with 95% confidence interval (CI) to identify risks factors for malnutrition associated with food neophobia and oral health., Results: Factors associated with the risk of malnutrition in the older population were higher food neophobia (adj-OR = 1.036, 95% CI: 1.007-1.067) and lower oral function (OR = 0.992, 95% CI: 0.985-0.999) and lower oral-health-related QOL (adj-OR = 0.963, 95% CI: 0.929-0.999)., Conclusions: Older adults at risk of developing malnutrition may have higher food neophobia and lower oral function and oral-health-related QOL. Factors contributing to preventing malnutrition include predicting the risk of malnutrition based on the oral health indicators that older people are aware of, signs appearing in the oral cavity, minor deterioration, and providing dietary guidance about food neophobia. Notably, these approaches represent novel strategies for nutrition support that can be implemented based on a multifaceted understanding of the eating habits of older adults., (© 2022. The Author(s).)

We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged <18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2,827 registered cases at 163 facilities, 2,348 cases were included. The rate of identified deaths compared with the demographic survey, was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows: 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsies. However, sufficient clinical information was not collected; therefore, thorough evaluations were difficult to perform. Cases with a moderate or high possibility of involvement of child maltreatment accounted for 5%, similar to previous studies. However, more objective evaluation is necessary. Preventable death cases including potentially preventable deaths accounted for 25%, indicating that proposals need to be made for specific preventive measures. Individual primary verification followed by secondary verification by multiple organizations is effective. It is anticipated that a child death review (CDR) system with such a multi-layered structure will be established; however, the following challenges were revealed: The subjects of CDR are all child deaths. Even if natural death cases are entrusted to medical organizations, and complicated cases to other special panels, the numbers are very high. Procedures need to be established to sufficiently verify these cases. Although demographic statistics are useful for identifying all deaths, care must be taken when interpreting such data. Detailed verification of the cause of death will affect the determination of subsequent preventability. Verification based only on clinical information is difficult, so a procedure that collates non-medical information sources should be established. It is necessary to organize the procedures to evaluate the involvement of child maltreatment objectively and raise awareness among practitioners. To propose specific preventive measures, a mechanism to ensure multiprofessional diverse perspectives is crucial, in addition to fostering the foundation of individual practitioners. To implement the proposed measures, it is also necessary to discuss the responsibilities and authority of each organization. Once the CDR system is implemented, verification of the system should be repeated. Efforts to learn from child deaths and prevent deaths that are preventable as much as possible are essential duties of pediatricians. Pediatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system. This is a word-for-word translation of the report in J. Jpn. Pediatr. Soc. 2019; 123 (11): 1736-1750, which is available only in the Japanese language., (© 2021 The Authors. Pediatrics International published by John Wiley & Sons Australia, Ltd on behalf of Japan Pediatric Society.)

Background: Nationwide antenatal human T-cell leukemia/lymphoma virus type-1 (HTLV-1) antibody screening has been conducted in Japan. The purpose of our study was to clarify the issues related to feeding options to prevent postnatal mother-to-child transmission., Methods: Of the pregnant carriers at 92 facilities in Japan between 2012 and 2015, 735 were followed prospectively. Among the children born to them, 313 (42.6%) children were followed up to the age of 3 and tested for HTLV-1 antibodies. The mother-to-child transmission rate was calculated for each feeding option selected before birth., Results: Among the 313 pregnant carriers, 55.0, 35.1, 6.1, and 3.8% selected short-term breast-feeding (≤3 months), exclusive formula feeding, frozen-thawed breast-milk feeding, and longer-term breast-feeding, respectively. Despite short-term breast-feeding, 8-18% of the mothers continued breast-feeding for 4-6 months. The mother-to-child transmission rate with short-term breast-feeding was 2.3% (4/172), and its risk ratio compared with that of exclusive formula feeding was not significantly different (0.365; 95% CI: 0.116-1.145). Because of the small number of children who were fed by frozen-thawed breast-milk, their mother-to-child transmission rate was not statistically reliable., Conclusions: Pregnant HTLV-1 carriers tended to select short-term breast-feeding in Japan. While short-term breast-feeding was not always easy to wean within 3 months, it may be a viable option for preventing postnatal mother-to-child transmission because the vertical transmission rate with short-term breast-feeding was not significantly higher than that with exclusive formula feeding. Increasing the follow-up rates for children born to pregnant carriers may provide clearer evidence of preventative effects by short-term breast-feeding and frozen-thawed breast-milk feeding., (© 2020 Japan Pediatric Society.)

Japan has been running a nationwide antenatal human T-cell leukemia virus type-1 (HTLV-1) antibody screening program since 2010 for the prevention of HTLV-1 mother-to-child transmission. As part of the program, pregnant women are invited to take an HTLV-1 antibody screening test, usually within the first 30 weeks of gestation, during regular pregnancy checkups. Pregnant women tested positive on the antibody screening test undergo a confirmatory test, either western blotting or line immunoassay. In indeterminate case, polymerase chain reaction (PCR) is used as a final test to diagnose infection. Pregnant women tested positive on a confirmatory or PCR test are identified as HTLV-1 carriers. As breastfeeding is a predominant route of postnatal HTLV-1 mother-to-child transmission, exclusive formula feeding is widely used as a postnatal preventive measure. Although there is insufficient evidence that short-term breastfeeding during ≤3 months does not increase the risk of mother-to-child transmission compared to exclusive formula feeding, this feeding method is considered if the mother is eager to breastfeed her child. However, it is important that mothers and family members fully understand that there is an increase in the risk of mother-to-child transmission when breastfeeding would be prolonged. As there are only a few clinical studies on the protective effect of frozen-thawed breastmilk feeding on mother-to-child transmission of HTLV-1, there is little evidence to recommend this feeding method. Further study on the protective effects of these feeding methods are needed. It is assumed that the risk of anxiety or depression may increase in the mothers who selected exclusive formula feeding or short-term breastfeeding. Thus, an adequate support and counseling for these mothers should be provided. In addition to raising public awareness of HTLV-1 infection, epidemiological data from the nationwide program needs to be collected and analyzed. In most cases, infected children are asymptomatic, and it is necessary to clarify how these children should be followed medically., (Copyright © 2020 Itabashi, Miyazawa, Sekizawa, Tokita, Saito, Moriuchi, Nerome, Uchimaru and Watanabe.)

Background: An increased risk of total death owing to human T-lymphotropic virus type-I (HTLV-I) infection has been reported. However, its etiology and protective factors are unclear. Various studies reported fluctuations in immune-inflammatory status among HTLV-I carriers. We conducted a matched cohort study among the general population in an HTLV-I-endemic region of Japan to investigate the interaction between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases., Method: We selected 2180 sub-cohort subjects aged 35-69 years from the cohort population, after matching for age, sex, and region with HTLV-I seropositives. They were followed up for a maximum of 10 years. Inflammatory gene polymorphisms were selected from TNF-α, IL-10, and NF-κB1. A Cox proportional hazard model was used to estimate the hazard ratio (HR) and the interaction between gene polymorphisms and HTLV-I for risk of total death and incidence of cancer and atherosclerosis-related diseases., Results: HTLV-I seropositivity rate was 6.4% in the cohort population. The interaction between TNF-α 1031T/C and HTLV-I for atherosclerosis-related disease incidence was statistically significant (p = 0.020). No significant interaction was observed between IL-10 819T/C or NF-κB1 94ATTG ins/del and HTLV-I. An increased HR for total death was observed in the Amami island region, after adjustment of various factors with gene polymorphisms (HR 3.03; 95% confidence interval, 1.18-7.77)., Conclusion: The present study found the interaction between TNF-α 1031T/C and HTLV-I to be a risk factor for atherosclerosis-related disease. Further follow-up is warranted to investigate protective factors against developing diseases among susceptible HTLV-I carriers., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

With our aging society, more people hope for a long and healthy life. In recent years, researchers have focused on healthy longevity factors. In particular, calorie restriction delays aging, reduces mortality, and extends life. Ghrelin, which is secreted during fasting, is well known as an orexigenic peptide. Because ghrelin is increased by caloric restriction, ghrelin may play an important role in the mechanism of longevity mediated by calorie restriction. In this review, we will discuss the role of orexigenic peptides with a particular focus on ghrelin. We conclude that the ghrelin-growth hormone secretagogue-R signaling pathway may play an important role in the anti-aging mechanism., Competing Interests: No author has relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Objectives: This study aimed to evaluate the usefulness of S100A12 and vascular endothelial growth factor (VEGF) for predicting the stability of remission for discontinuing methotrexate (MTX) and/or biological agents in Japanese patients with oligo/polyarticular juvenile idiopathic arthritis (JIA)., Methods: Forty-four patients with oligo/polyarticular JIA who received MTX with or without biological agents were enrolled. Serum concentration of both S100A12 and VEGF were simultaneously evaluated by ELISA in active and in remission phase determined by activity markers including DAS-28., Results: S100A12 and VEGF were correlated with DAS-28. Of the 22 patients with oligo/polyarticular JIA in clinical remission, 13 patients with low S100A12 and VEGF concentrations could discontinue treatment without relapse over 2 years. However, nine patients without low S100A12 and VEGF concentrations relapsed afterwards, even though they had been in clinical remission. The cut-off levels of S100A12 and VEGF for division into two groups of the maintenance remission and relapse groups were 177 ng/ml and 158 pg/ml, respectively., Conclusions: S100A12 and VEGF are useful markers for assessing disease activity of oligo/polyarticular JIA in remission phase. These markers should be kept low when clinicians consider tapering or discontinuing treatments in oligo/polyarticular JIA patients.

Aim: Observational studies have reported that elevated homocysteine (Hcy) levels are associated with the risk of cardiovascular disease (CVD). However, interventions that lower Hcy do not provide a corresponding risk reduction. Therefore, the causal role of Hcy in CVD remains unclear. This 5-year prospective study investigated the associations of Hcy levels, folate intake, and host factors with arterial stiffness among the general Japanese population., Methods: We prospectively recruited 658 participants (40-69 years old) from the general population during regular health checkup examinations. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) at baseline and the 5-year follow-up. Folate intake was estimated using a structured questionnaire. Genotyping was used to evaluate the MTHFR C677T and MS A2756G gene polymorphisms. Ultrafast liquid chromatography was used to measure total plasma Hcy levels. Association between these variables and CAVI values was evaluated using general linear regression and logistic regression models that were adjusted for atherosclerosis-related factors., Results: Men had higher Hcy levels and CAVI values and lower folate intake than women (all, p＜0.001). At baseline, Hcy, folate intake, and the two genotypes were not associated with CAVI values for both sexes. Among men, Hcy levels were positively associated with CAVI values at the 5-year follow-up (p=0.033). Folate intake and the two genotypes were not associated with the 5-year CAVI values., Conclusion: Plasma Hcy may be involved in arterial stiffness progression, as monitored using CAVI, among men.

Objective: To clarify polyarticular juvenile idiopathic arthritis (pJIA) patients who failed to maintain prolonged remission with the first biologic agent., Methods: Fourteen pJIA patients were observed for 47.5 months (median) after initiating the first biologic agent., Results: Eight maintained sustained clinical remission (median 47 months) with the first biologic agents, while the six switched to the second one due to lack of efficacy, thereafter. Receiver operating characteristic (ROC) analysis revealed that disease activity score in 28 joints (DAS28) of 2.37 at 3 months could distinguish between the two patient groups (p = 0.001)., Conclusion: pJIA patients with DAS28 >2.37 at 3 months of the initial biologic therapy may be considered to switch to the second biologics.

Objectives: To evaluate the safety and effectiveness of hepatitis B virus (HBV) vaccination in patients with juvenile idiopathic arthritis (JIA) controlled by treatment., Methods: Among 49 patients with juvenile idiopathic arthritis (JIA) at the outpatient clinic of Kagoshima University Hospital, we enrolled 25 who were controlled by treatment. All children were unimmunized and were vaccinated against HBV according to the schedule. Their responses to the vaccine and vaccine adverse events were examined during their visits., Results: Nineteen of the 25 patients with JIA controlled by treatment developed effective antibody responses (76%). All eight patients with JIA below 10 years of age achieved seroconversion. The seroconversion was not influenced by biologics. Five adverse events were observed (6.7%). The rate of all adverse events did not surpass that of a previous report, and all adverse events were immediately resolved. None of the patients with JIA experienced a flare-up or clinical deterioration related to the vaccination., Conclusions: HBV vaccination is safe and effective. Pediatric rheumatologists should consider HBV vaccination for unimmunized patients with JIA, because the response to HBV vaccine might be influenced by age, and children have a higher risk for potential HBV infection than adults.

Complementary and alternative medicine (CAM) including Japanese Kampo is known to have anticancer potential. An increasing number of cancer survivors are using CAM for disease prevention, immune system enhancement, and symptom control. Although there have been abundant previous clinical reports regarding CAM, scientific investigations aimed at acquiring quantifiable results in clinical trials, as well as basic research regarding CAM, have only recently been undertaken. Recent studies suggest that CAM enhancement of immune function is related to cytokines. This review provides a translational aspect of CAM, particularly Hozai in Kampo from both scientific and clinical points of view for further development of CAM for cancer treatment.

Endoscopy is now being used for breast cancer surgery. Though it is used for mastectomy, lymph node dissection, and breast reconstruction, its prime use is for mastectomy. Because an incision can be placed inconspicuously in the axillary site, a relatively large incision can be created. A retractor with an endoscope, CO2, and an abrasion device with the endoscope are used for operation space security. It is extremely rare that an endoscope is used for lymph node dissection. For breast reconstruction, it may be used for latissimus muscle flap making, but an endoscope is rarely used for other reconstructions. Endoscopic mastectomy is limited to certain institutions and practiced hands, and it has not been significantly developed in breast cancer surgery. On the other hand, endoscopic surgery may be used widely in breast reconstruction. With respect to the spread of robotic surgery, many factors remain uncertain.

The aim of this study was to assess the current human T-cell lymphotropic virus type 1 (HTLV-I) mother-to-child transmission (MTCT) prevention system in Kagoshima Prefecture. We investigated the rate of carrier pregnant women from obstetrics facilities in Kagoshima by mail in 2012 and compared our results with previous study results. We interviewed carrier pregnant women about their choices for infant nutrition, and we interviewed midwives about the follow-up system. In 2012, 8719 screening tests were performed, covering 58.1% of all pregnant women in Kagoshima; the rate of carrier pregnant women was 1.3%. Of 59 carriers, 39 chose short-term breast-feeding. The HTLV-I carrier rate among pregnant women in Kagoshima has declined. The current HTLV-I MTCT prevention system in Kagoshima is effective, but not sufficient. To bring the nutrition methods to completion, various types of support are needed. Further studies will elucidate many unsolved problems concerning MTCT., (© 2014 Japan Pediatric Society.)

Background: Inflammatory gene polymorphisms are potentially associated with atherosclerosis risk, but their age-related effects are unclear. To investigate the age-related effects of inflammatory gene polymorphisms on arterial stiffness, we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness., Methods: We recruited 1850 adults aged 34 to 69 years from the Japanese general population. Inflammatory gene polymorphisms were selected from NF-kB1, CD14, IL-6, IL-10, MCP-1, ICAM-1, and TNF-α. Associations of CAVI with genetic and conventional risk factors were estimated by sex and age group (34-49, 50-59, and 60-69 years) using a general linear model. The association with 5-year change in CAVI was examined longitudinally., Results: Glucose intolerance was associated with high CAVI among women in all age groups, while hypertension was associated with high CAVI among participants in all age groups, except younger women. Mean CAVI for the CD14 CC genotype was lower than those for the TT and CT genotypes (P for trend = 0.005), while the CD14 polymorphism was associated with CAVI only among men aged 34 to 49 years (P = 0.006). No association of the other 6 polymorphisms with CAVI was observed. No association with 5-year change in CAVI was apparent., Conclusions: Inflammatory gene polymorphisms were not associated with arterial stiffness. To confirm these results, further large-scale prospective studies are warranted.

Objectives: Previous short-term trials found etanercept (0.2 or 0.4 mg/kg) to be effective and well tolerated in Japanese children with juvenile idiopathic arthritis (JIA) who were intolerant/resistant to methotrexate. The aim of this study was to evaluate the long-term safety and efficacy of etanercept in Japanese children with JIA., Methods: Patients (4-19 years) who received etanercept in one of three short-term studies continued onto this long-term open-label study., Results: Of the 32 patients enrolled, 18 (56.3%) completed 192 weeks of the study and 14 (43.8%) were discontinued; 7 (21.9%) for patient refusal, 2 (6.3%) for adverse events (AEs), and 5 (15.6%) for lack of efficacy. All patients reported AEs; 31 (96.9%) reported infections and 6 (18.8%) reported serious AEs. Main efficacy assessments included change from baseline in the American College of Rheumatology Pediatric core components, including mean improvements from baseline in the physician global assessment (90.7%), patient/guardian global assessments (54.1%), Childhood Health Assessment Questionnaire (84.6%), and median improvements in C-reactive protein levels (92.7%). No unexpected safety results were reported, and early efficacy responses were sustained in the long term., Conclusions: This study provides further evidence that etanercept is an effective therapeutic option for Japanese children with polyarticular-course JIA.

We evaluated the safety and efficacy of tocilizumab in polyarticular-course juvenile idiopathic arthritis (pJIA) with polyarticular or oligoarticular onset. Patients received 8 mg/kg tocilizumab every 4 weeks in the open-label studies: initial study (to week 12) and then an extension study (at least 48 weeks). Nineteen patients intractable to conventional methotrexate therapy were enrolled. Seventeen patients had polyarticular-onset pJIA; two had oligoarticular-onset pJIA. Mean age was 11.6 years; mean disease duration 5.3 years. American College of Rheumatology Pediatric (ACR Pedi) 30, 50, 70, and 90 response rates, respectively, were 94.7%, 94.7%, 57.9%, and 10.5% at week 12, and 100%, 94.1%, 88.2%, and 64.7% at week 48. Mean disease activity score (DAS28) remained below the remission level (2.6) from week 24. Administration was discontinued in two patients during the extension study because the ACR Pedi 50 response was judged insufficient (one patient) and antitocilizumab antibodies developed (one patient). Adverse events were generally mild, and the four serious adverse events resolved spontaneously or with treatment. In conclusion, tocilizumab showed early and sustained efficacy and tolerability for treating intractable pJIA, which suggests that it is a promising new treatment for this disease.

Efficacy, safety, and pharmacokinetics results from 4 studies-3 open-label (OL) and 1 randomized double-blind (DB)-have provided data for approval of etanercept for treatment of disease-modifying anti-rheumatic drug (DMARD)-refractory juvenile idiopathic arthritis (JIA) in Japan. Results from the 3 shorter-term (2 OL and 1 DB) studies are reported here. Subjects (4-17 years) enrolled in the OL studies had active JIA, i.e. ≥5 swollen joints and ≥3 joints with limitation of motion and pain or tenderness. Subjects enrolled in the primary OL study received etanercept 0.4 mg/kg subcutaneously twice weekly; in the lower-dose OL study subjects received etanercept 0.2 mg/kg. Subjects in the primary OL study who completed ≥48 weeks could continue into a 12-week DB dose-down extension study in which subjects received etanercept 0.4 or 0.2 mg/kg twice weekly. The primary endpoint in all 3 studies, i.e. 30% improvement in the American College of Rheumatology criteria for JIA (ACR Pedi 30) at 12 weeks, was achieved by ≥80% of subjects by week 2 and sustained to week 12. Common adverse events reported were injection site reactions, nasopharyngitis, and gastroenteritis. These results provide further evidence that etanercept is effective therapy for DMARD-refractory polyarticular JIA patients.

We herein report a 3 year-old boy, who showed proximal muscle weakness and pain at the age of one and a-half years. When he visited our hospital at the age of 1 year and 11 months, he could hardly move by himself. He also had difficulty in swallowing and suffered from multiple dermal ulcers. His blood test showed slightly elevated muscle enzyme activity, and magnetic resonance imaging suggested severe inflammation of the muscles. Radiological examination proved hypoperistalsis of the esophagus. With additional skin and muscle biopsies, we diagnosed him with juvenile dermatomyositis (JDM). Methyl-prednisolone pulse therapy was not effective enough, thus oral methotrexate, cyclosporine A and monthly cyclophosphamide pulse therapy were added. After the fourth cyclophosphamide pulse therapy, his muscular strength was restored, and the ulcers healed dramatically. Due to scarcity of severe cases, neither standardized classification nor grading system for severity in JDM has ever been established, which perplexes physicians in finding the best therapeutic strategy. Further investigation, experience and efforts are necessary to standardize an evaluating system and therapeutic strategy against JDM.

We report a 27-year-old case of juvenile idiopathic arthritis (JIA) having been stopped infliximab during pregnancy. She was safely treated by infliximab therapy with premedications for preventing infusin reactions after her delivery, and then improved in the same manner as when she had been treated with infliximab therapy before pregnancy. As a result, it remains unclear whether or not we can use infliximab to control disease activities during pregnancy. In addition, it is also important to clarify whether or not premedications should be used when resuming infliximab treatment in such patients after pregnancy. These problems still remain controversial. More definitive data are needed in order to allow rheumatologists to better select the optimal TNF-alpha inhibitor therapy when treating pregnant JIA patients.

Tumor necrosis factor alpha (TNFalpha)-blocking agents have been used increasingly in the treatment of severe refractory juvenile idiopathic arthritis (JIA). However, some patients have been forced to discontinue these agents because of the lack of efficacy or adverse events. In these situations, cases of switching from one TNF-blocking agent to another are reported in rheumatoid arthritis, but there are few cases in JIA. This report documents the case of a patient with JIA who improved following a switch from etanercept to infliximab.

There is no nationwide outbreak of rubella after 1992 in Japan, but a local outbreak remains. Recently, some cases of congenital rubella syndrome (CRS) were reported after a local outbreak. An outbreak of rubella among hospital personnel occurred in our hospital located on Tanegashima Island on March and April 2003 after a visit of one rubella patient. Fifteen employees, including 7 clerks, 6 nurses, one doctor, and one radiologist, experienced rubella. A total of 259 employees in our hospital employees were examined for anti rubella hemagglutination inhibition (HI) tests with informed consent and recommended to take rubella vaccines. Sixty-seven employees (26%) among 257 examined for tests were found susceptible to rubella, and 53 employees were vaccinated. After vaccination, the outbreak was stamped out immediately. There was no rubella patient infected from employee. Nine among the 15 infected employees had declared to have a history of rubella or rubella vaccines before onsets, suggesting interviews are not reliable. There were many susceptible persons and rubella patients among elderly women and male personnel; therefore, measures are needed for elderly personnel as well as younger employees. In addition, adequate measures should be taken to prevent CRS, because many female personnel capable of pregnancy work in hospitals. The cost of the rubella HI tests and vaccination was approximately yen 200,000 (about dollar 1,600). The absence due to illness per one person was 6 days, and the wage per one day was about yen 12,000 (about dollar 100) on the average. The overall cost required in the outbreak was estimated to be approximate yen 1,400,000 (about dollar 12,000). Considering that an outbreak of rubella causes not only a large amount of expenditure but also loss of hospital income, the investment to prevent a rubella outbreak is quite valuable in the management of a hospital.

In Sjögren syndrome, purpura is one of its various well known eruptions. Although this disease state is assumed to be based on hypergammaglobulinemia, the details of its mechanism are unknown. We experienced a case involving a female patient with primary Sjögren syndrome showing repeated purpura on the legs, and examined her blood viscosity and histopathology. This girl developed Sjögren syndrome and was admitted to our hospital at 12-years-old. She underwent steroid treatment because of aggravation of the xerosis state and prominent purpura on the legs. Hypergammaglobulinemia was improved during the course; however, purpura appeared repeatedly. Although her blood viscosity was slightly higher than normal, this had no relation to purpura and serum gamma globulin values. Skin biopsy revealed necrotizing angiitis. These results suggest that the purpura of this case was caused not only by hyperviscosity from the hypergammaglobulinemia but also involvement of vasculitis by the primary disease.

In order to discuss the diversity of clinical features and the difficulty in diagnosis of children with juvenile rheumatoid arthritis (JRA), we present two cases who have documented the development of systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) after a long period of disease characterized only by arthritis that was initially diagnosed as JRA. The first case was a girl diagnosed for her arthritic joints as polyarticular JRA at 15 years of age. At onset, she had Raynaud phenomenon but autoantibodies such as anti-nuclear antibody (ANA), anti-DNA antibody, and rheumatoid factor were negative. Five years after onset, she became ANA positive and 3 years later she became pregnant. During her pregnancy, she became positive for anti-DNA antibody without any signs of nephritis. One month after the delivery, however, she developed butterfly rash, carditis, nephritis, and was diagnosed as SLE. No destructive changes were observed in her joints though arthritis continued for 8 years form onset to pregnancy. The second case was a 3 years old girl who was diagnosed as polyarticular JRA. Treatment by aspirin induced complate remission after one year from the onset. However, 10 years after that remission, she developed Raynaud phenomenon and arthralgia in her knees and hip joints. Her laboratory findings showed hypergammaglobulinemia, positive ANA, positive anti-DNA antibody, positive anti-RNP antibody. She was eventually diagnosed as MCTD when she was found to have polymyositis by EMG and serum CK. In the present paper, two cases imply the difficulty in diagnosing JRA and diversity of rheumatic diseases such as JRA, SLE and MCTD. Closer and longer period of observation is essential for the JRA patients with nondestructive arthritis.

Marked advances have been made in the past decade in the management of adults with systemic lupus erythematosus (SLE). Therefore, a nationwide retrospective survey was conducted between 1980 and 1994 to investigate the clinical manifestations of SLE in Japanese children and adolescents. Questionnaires were sent to 340 hospitals. Of 405 patients reported by 176 hospitals, 373 patients, diagnosed by the criteria established by the Pediatric Study Group of the Japanese Ministry of Health and Welfare in 1985, were enrolled in the study. Forty-nine of the 354 patients (13.8%) had relatives with a connective tissue disease within the third degree of consanguinity. The frequent manifestations in 373 patients were the presence of antinuclear antibody (98.9%), immunologic disorders (93.0%), hypocomplementemia (87.1%), malar rash (79.6%) and fever (74.0%). Lupus nephritis was present in 148 of the 309 patients (47.9%) at their first visit to a clinic, and 261 of the 373 patients (70.0%) developed renal involvement during the observation period. Of 370 patients, 92 patients (24.9%) exhibited central nervous system lupus. Of 368 patients, 192 patients (52.2%) were treated by methylprednisolone pulse therapy and 148 patients (40.2%) received immunosuppressants in combination with steroid therapy at some stage during the observation period, Survival rate at 5 years from onset was 95.9%. Management of infection, coagulopathies, and central nervous system involvement is essential to improve the prognosis of SLE in Japanese children and adolescents.