Gene signature of children with severe respiratory syncytial virus infection.

BACKGROUND: The limited treatment options for children with severe respiratory syncytial virus (RSV) infection highlights the need for a comprehensive understanding of the host cellular response during infection. We aimed to identify host genes that are associated with severe RSV disease and to identify drugs that can be repurposed for the treatment of severe RSV infection. METHODS: We examined clinical data and blood samples from 37 hospitalized children (29 mild and 8 severe) with RSV infection. We tested RNA from blood samples using next-generation sequencing to profile global mRNA expression and identify cellular processes. RESULTS: Retractions, decreased breath sounds, and tachypnea were associated with disease severity. We observed upregulation of genes related to neutrophil, inflammatory response, blood coagulation, and downregulation of genes related to T cell response in children with severe RSV. Using network-based approach, 43 drugs were identified that are predicted to interact with the gene products of these differentially expressed genes. CONCLUSIONS: These results suggest that the changes in the expression pattern in the innate and adaptive immune responses may be associated with RSV clinical severity. Compounds that target these cellular processes can be repositioned as candidate drugs in the treatment of severe RSV. IMPACT: Neutrophil, inflammation, and blood coagulation genes are upregulated in children with severe RSV infection. Expression of T cell response genes are suppressed in cases of severe RSV. Genes identified in this study can contribute in understanding the pathogenesis of RSV disease severity. Drugs that target cellular processes associated with severe RSV can be repositioned as potential therapeutic options.

A Facile Method for the Quantification of Urinary Uracil Concentration by a Uracil-Specific Fluorescence Derivatization Reaction.

A facile and reliable fluorescence method for the quantification of urinary uracil concentration is proposed herein. The assay utilizes a specific fluorescence (FL) derivatization reaction for uracil using 3-methylbenzamidoxime as a fluorogenic reagent. Although the presence of urine inhibited the FL reaction, 10 µL of urine was sufficient for the detection of urinary uracil. The uracil derivative was successfully separated from other fluorescent impurities using simple reversed-phase LC with FL detection. Urinary uracil concentrations from 16 people were compared with the concentrations obtained by the traditional column-switching liquid chromatographic analysis with UV detection. The FL derivative of uracil appeared as a single peak in the chromatograms of all samples. However, several samples showed an additional peak overlapping the uracil peak when using the column-switching method because of UV-active impurities. These results indicated that that the present method is not affected by interfering substances in urine and affords a precise determination of urinary uracil. We expect the proposed method to be applicable for diagnosing dihydropyrimidine dehydrogenase deficiency in 5-fluorouracil chemotherapy.

Comparison between patient-reported and clinician-reported outcomes: Validation of the Japanese version of the Integrated Palliative care Outcome Scale for staff.

OBJECTIVES: The goal of palliative and supportive care is to improve patients' quality of life (QoL). Patient-reported outcome measures (PROMs) are the gold standard for the assessment of QoL and symptoms; however, when self-reporting is complicated, PROMs are often substituted with proxy-reported outcome measures, such as clinician-reported outcome measures. The objective of this study was to assess the validity and reliability of the Japanese version of the Integrated Palliative care Outcome Scale (IPOS) for staff (IPOS-Staff). METHODS: This multicenter, cross-sectional observational study was conducted concurrently with the validation of the IPOS for patients (IPOS-Patient). Japanese adult patients with cancer and their staff were recruited. We assessed the characteristics of the patients and staff members, missing values, prevalence, and total IPOS scores. For the analysis of criterion validity, intra-rater, and inter-rater reliability, we calculated intraclass correlations (ICCs). RESULTS: One hundred and forty-three patients completed the IPOS-Patient, and 79 medical staff members completed the IPOS-Staff. The most common missing values from IPOS-Staff were Family Anxiety (3.5%) and Sharing Feelings (3.5%). Over half of the patients scored themselves moderate or worse for Poor Mobility, Anxiety, and Family Anxiety, while staff members scored patients moderate or worse for Weakness, Anxiety, and Family Anxiety. For criterion validity (patient-staff agreement) as well as intra-rater and inter-rater reliability, ICCs ranged from 0.114 (Sharing Feelings) to 0.826 (Nausea), 0.720 (Anxiety) to 0.933 (Nausea), and -0.038 (Practical Problems) to 0.830 (Nausea), respectively. SIGNIFICANCE OF RESULTS: The IPOS-Staff is easy to respond to; it has fair validity and reliability for physical items but poor for psycho-social items. By defining the context and objectives of its use and interpretation, the IPOS-Staff can be a useful tool for measuring outcomes in adult patients with cancer who cannot complete self-evaluations.

How successful are we in relieving terminal dyspnea in cancer patients? A real-world multicenter prospective observational study.

PURPOSE: Parenteral morphine is widely used for dyspnea of imminently dying cancer patients, but the outcomes to expect over time remain largely unknown. We examined outcomes after the administration of parenteral morphine infusion over 48 h in cancer patients with a poor performance status. METHODS: This was a multicenter prospective observational study. Inclusion criteria were metastatic/locally advanced cancer, ECOG performance status = 3-4, a dyspnea intensity ≥ 2 on a Support Team Assessment Schedule, Japanese version (STAS-J), and receiving specialized palliative care. After initiating parenteral morphine infusion, we measured dyspnea STAS-J as well as Memorial Delirium Assessment Scale (MDAS), item 9, and Communication Capacity Scale (CCS), item 4, every 6 h over 48 h. RESULTS: We enrolled 167 patients (median survival = 4 days). The mean age was 70 years, 80 patients (48%) had lung cancer, and 109 (65%) had lung metastases. The mean STAS-J scores decreased from 3.1 (95% confidence interval (CI) = 3.0-3.2) at the baseline to 2.1 (95%CI = 1.9-2.2) at 6 h, and remained 1.6-1.8 over 12-48 h. The proportion of patients with dyspnea relief (STAS-J ≤ 1) increased to 39% at 6 h, and ranged between 49 and 61% over 12-48 h. In contrast, up to 6.6 and 20% of patients showed hyperactive delirium (MDAS item 9 ≥ 2) and an inability to communicate (CCS item 4 = 3), respectively, over 48 h. CONCLUSIONS: Overall, terminal dyspnea was relatively well controlled with parenteral morphine, though a significant number of patients continued to suffer from dyspnea. Future efforts are needed to improve outcomes following standardized dyspnea treatment using patient-reported outcomes for imminently dying patients.

Validation of the Integrated Palliative care Outcome Scale (IPOS) - Japanese Version.

BACKGROUND: To improve palliative care practice, the need for patients-reported outcome measures is increasing globally. The Integrated Palliative care Outcome Scale (IPOS) is a streamlined outcome scale developed to comprehensively evaluate patients' distress. The goal of this study is to assess the reliability and validity of IPOS-Japanese version in cancer patients. METHODS: This is a multicenter, cross-sectional observational study. We assessed the missing values, prevalence, test-retest reliability, criterion validity and known-group validity in Japanese adult cancer patients. Patients provided responses to IPOS, European Organization for Research and Treatment for Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and Functional Assessment of Chronic Illness Therapy- Spiritual 12 (FACIT-Sp12). Our medical staff provided responses to Support Team Assessment Schedule (STAS). RESULTS: One hundred forty-two patients were enrolled at six palliative care facilities. Missing values accounted for less than 1% of most items, with a maximum of 2.8%. The prevalence of symptoms was 17.7-88.7%. The intra-class correlation coefficient ranged from 0.522 to 0.951. The range of correlation coefficients with EORTC-QLQ-C30, FACIT-Sp12 and STAS as gold standards was 0.013 to 0.864 (absolute values). Total IPOS scores were positively correlated with Eastern Corporative Oncology Group Performance Status (P < 0.001). CONCLUSION: IPOS-Japanese version is a valid and reliable tool. The scale is useful in assessing physical, psychological, social and spiritual symptoms and in measuring outcomes of adult cancer patients in Japan.

First report on USA300 outbreak in a neonatal intensive care unit detected by polymerase chain reaction-based open reading frame typing in Japan.

Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) in the neonatal intensive care unit (NICU) have been reported worldwide. Some outbreaks were caused by USA300, which is a community-associated MRSA clone. In 2011, polymerase chain reaction-based open reading frame typing (POT) for the initial MRSA isolates from all inpatients was started at the Tokyo Metropolitan Children's Medical Center. From March 2014 to April 2015, a total of 131 MRSA strains were isolated, 104 of which were analyzed as healthcare-associated MRSA. Thirteen stains (12.5%) had a POT number of 106-9-93, which strongly suggested USA300; these included 6 from nasal swabs, 6 from blood cultures and 1 from subcutaneous pus. All the MRSA strains were isolated from patients in the NICU; were typed as sequence type 8, spa type t008, and staphylococcal cassette chromosome type mec IVa; and possessed the lukS-lukF and arginine catabolic mobile element-arcA gene. Pulsed-field gel electrophoresis of all the strains, with USA300-0114 as a reference, showed indistinguishable banding pattern. Based on these results, POT was useful in recognizing this first MRSA outbreak of USA300 in a Japanese NICU and was advantageous in terms of swiftness, less cost and monitoring change of the epidemic MRSA lineage.

Predictors of response to corticosteroids for dyspnea in advanced cancer patients: a preliminary multicenter prospective observational study.

PURPOSE: Although corticosteroids can relieve dyspnea in advanced cancer patients, factors predicting the response remain unknown. We aimed to explore potential factors predicting the response to corticosteroids for dyspnea in advanced cancer patients. METHODS: In this preliminary multicenter prospective observational study, we included patients who had metastatic or locally advanced cancer, were receiving specialized palliative care services, and had a dyspnea intensity of ≥3 on a 0-10 Numerical Rating Scale (NRS) (worst during the last 24 h). The primary endpoint was NRS of dyspnea on day 3 after the administration of corticosteroids. Univariate/multivariate analyses were conducted to identify factors predicting ≥1-point reduction in NRS. RESULTS: Of 74 patients who received corticosteroids, 50 (68%) showed ≥1-point reduction in dyspnea NRS. Factors that significantly predicted the response were an age of 70 years or older (82 vs. 53%, p = 0.008), absence of liver metastases (77 vs. 46%, p = 0.001), Palliative Prognostic Index (PPI) ≤ 6 (90 vs. 61%, p = 0.041), presence of pleuritis carcinomatosa with a small collection of pleural effusions (84 vs. 55%, p = 0.011), presence of audible wheezes (94 vs. 60%, p = 0.014), and baseline dyspnea NRS ≥7 (76% vs. 52%, p = 0.041). In a multivariate analysis, factors predicting response included PPI <6 (odds ratio (OR), 36.2; p = 0.021), baseline dyspnea NRS (worst) ≥7 (OR, 6.6; p = 0.036), and absence of liver metastases (OR, 0.19; p = 0.029) or ascites/liver enlargement (OR, 0.13; p = 0.050). CONCLUSIONS: The patient characteristics, etiologies of dyspnea, and clinical manifestations may predict responses to corticosteroids for dyspnea. Larger prospective studies are promising to confirm our findings.

Predictors of responses to corticosteroids for anorexia in advanced cancer patients: a multicenter prospective observational study.

PURPOSE: Although corticosteroids are widely used to relieve anorexia, information regarding the factors predicting responses to corticosteroids remains limited. The purpose of the study is to identify potential factors predicting responses to corticosteroids for anorexia in advanced cancer patients. METHODS: Inclusion criteria for this multicenter prospective observational study were patients who had metastatic or locally advanced cancer and had an anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting ≥2-point reduction in NRS on day 3. RESULTS: Among 180 patients who received corticosteroids, 99 (55 %; 95 % confidence interval [CI], 47-62 %) had a response with ≥2-point reduction. Factors that significantly predicted responses were Palliative Performance Scale (PPS) > 40 and absence of drowsiness. In addition, factors that tended to be associated with ≥2-point reduction in NRS included PS 0-3, absence of diabetes mellitus, absence of peripheral edema, presence of lung metastasis, absence of peritoneal metastasis, baseline anorexia NRS of >6, presence of pain, and presence of constipation. A multivariate analysis showed that the independent factors predicting responses were PPS of >40 (odds ratio = 2.7 [95 % CI = 1.4-5.2]), absence of drowsiness (2.6 [1.3-5.0]), and baseline NRS of >6 (2.4 [1.1-4.8]). CONCLUSIONS: Treatment responses to corticosteroids for anorexia may be predicted by PPS, drowsiness, and baseline symptom intensity. Larger prospective studies are needed to confirm these results.

Analysis of follow-up data from an outpatient pain management program for refractory chronic pain.

BACKGROUND: Numerous reports indicate that multifaceted pain management programs based on cognitive-behavioral principles are associated with clinically meaningful long-term improvements in chronic pain. However, this has not yet been investigated in Japan. This study investigated the effects of a multifaceted pain management program in Japanese patients with chronic pain, both immediately after the program and 6 months thereafter. METHODS: A total of 96 patients, 37 male and 59 female (mean age 63.8 years) experiencing treatment difficulties and suffering from intractable pain for more than 6 months were enrolled in the study. The programs were conducted with groups of 5-7 patients who met weekly for 9 weeks. Weekly sessions of approximately 2 h in duration incorporating a combination of lectures and exercise were conducted. Several measures related to pain and physical function were assessed at the start of the program, the end of the program, and 6 months after completion of the program. The resulting data were analyzed via Wilcoxon signed-rank test, and 'r' estimated by effect size was also assessed. RESULTS: Of the 96 initial participants, 11 dropped out during the program and 85 completed it. Thereafter, we evaluated 62 subjects at 6 months after the program, while 23 could not be evaluated at that time-point. Pain intensity upon moving, catastrophizing scores, and pain disability scores showed good improvements at the 6-month follow-up, with large efficacy (r > 0.5). Moving capacity and 6-min walking distance also showed good improvements with large efficacy, both at the end of the program and at the 6-month follow-up (r > 0.5). CONCLUSIONS: A multifaceted pain-management program based on cognitive-behavioral principles was effective in Japanese patients with chronic pain, resulting in improved long-term clinical outcomes.

Multicenter cohort study on the survival time of cancer patients dying at home or in a hospital: Does place matter?

BACKGROUND: Although the place of death has a great influence on the quality of death and dying for cancer patients, whether the survival time differs according to the place of death is unclear. The primary aim of this study was to explore potential differences in the survival time of cancer patients dying at home or in a hospital. METHODS: This multicenter, prospective cohort study was conducted in Japan from September 2012 through April 2014 and involved 58 specialist palliative care services. RESULTS: Among the 2426 patients recruited, 2069 patients were analyzed for this study: 1582 receiving hospital-based palliative care and 487 receiving home-based palliative care. A total of 1607 patients actually died in a hospital, and 462 patients died at home. The survival of patients who died at home was significantly longer than the survival of patients who died in a hospital in the days' prognosis group (estimated median survival time, 13 days [95% confidence interval (CI), 10.3-15.7 days] vs 9 days [95% CI, 8.0-10.0 days]; P = .006) and in the weeks' prognosis group (36 days [95% CI, 29.9-42.1 days] vs 29 days [95% CI, 26.5-31.5 days]; P = .007) as defined by Prognosis in Palliative Care Study predictor model A. No significant difference was identified in the months' prognosis group. Cox proportional hazards analysis revealed that the place of death had a significant influence on the survival time in both unadjusted (hazard ratio [HR], 0.86; 95% CI, 0.78-0.96; P < .01) and adjusted models (HR, 0.87; 95% CI, 0.77-0.97; P = .01). CONCLUSIONS: In comparison with cancer patients who died in a hospital, cancer patients who died at home had similar or longer survival. Cancer 2016;122:1453-1460. © 2016 American Cancer Society.

Glasgow prognostic score predicts prognosis for cancer patients in palliative settings: a subanalysis of the Japan-prognostic assessment tools validation (J-ProVal) study.

PURPOSE: The Glasgow prognostic score (GPS), which uses C-reactive protein and albumin levels, is a good predictor of prognosis in cancer patients undergoing anti-tumor therapy. The objective of this study was to investigate the correlation between GPS and survival among cancer patients in palliative settings, as findings in such populations have not been well described. METHODS: This was a subanalysis of a multicenter, prospective, cohort study in patients who were adults, diagnosed with advanced cancer, and first referred to palliative care service in Japan. Patients who were not receiving anti-tumor therapy and who had undergone laboratory examinations were eligible. Clinical features were analyzed to investigate prognostic factors. RESULTS: A total of 1160 patients were enrolled (41.6 % female; median age, 72 years). The independent predictors were Eastern Cooperative Oncology Group performance status (ECOG PS) score of 4 (hazard ratio (HR), 1.54), liver metastasis (HR, 1.21), dyspnea (HR, 1.35), edema (HR, 1.25), prognostic performance index (HR, 1.56), neutrophil-lymphocyte ratio (HR, 1.43), and GPS of 2 (HR, 1.36). The sensitivity and specificity for 3-week prognosis of a GPS of 2 were 0.879 and 0.410. Median survival time with GPS of 0, 1, and 2 was 58 days (95 % confidence interval, 48-81), 43 days (37-50), and 21 days (19-24), respectively (log-rank test, p < 0.001). CONCLUSION: The GPS was a good prognostic indicator for cancer patients in palliative settings.

[Transdermal System-Buprenorphine and Fentanyl].

Pain management with transdermal opioids is a useful choice in light of longer duration of action, being not affected by oral intake, and with less adverse effect Recently, transdermal fentanyl and buprenorphine are permitted for musculoskeletal non-malignant pain as a new indication. In Japan, one of the world's fastest aging society, it is a welcome step in terms of pain control. However, proper monitoring and management are required. This article reviews the pharmacology, therapeutic efficacy and adverse effect of buprenorphine transdermal patch, and clinical application in cancer pain management of fentanyl patch.

Activated spinal astrocytes are involved in the maintenance of chronic widespread mechanical hyperalgesia after cast immobilization.

BACKGROUND: In the present study, we examined spinal glial cell activation as a central nervous system mechanism of widespread mechanical hyperalgesia in rats that experienced chronic post-cast pain (CPCP) 2 weeks after cast immobilization. Activated spinal microglia and astrocytes were investigated immunohistologically in lumbar and coccygeal spinal cord segments 1 day, 5 weeks, and 13 weeks following cast removal. RESULTS: In the lumbar cord, astrocytes were activated after microglia. Astrocytes also were activated after microglia in the coccygeal cord, but with a delay that was longer than that observed in the lumbar cord. This activation pattern paralleled the observation that mechanical hyperalgesia occurred in the hindleg or the hindpaw before the tail. The activating transcription factor 3 (ATF3) immune response in dorsal root ganglia (DRG) on the last day of cast immobilization suggested that nerve damage might not occur in CPCP rats. The neural activation assessed by the phosphorylated extracellular signal-regulated kinase (pERK) immune response in DRG arose 1 day after cast removal. In addition, L-α-aminoadipate (L-α-AA), an inhibitor of astrocyte activation administered intrathecally 5 weeks after cast removal, inhibited mechanical hyperalgesia in several body parts including the lower leg skin and muscles bilaterally, hindpaws, and tail. CONCLUSIONS: These findings suggest that activation of lumbar cord astrocytes is an important factor in widespread mechanical hyperalgesia in CPCP.

The effect of celiac plexus block on heart rate variability.

BACKGROUND: Celiac plexus block (CPB) can be used for treating intra-abdominal visceral pain syndromes. The celiac plexus is the largest plexus of the sympathetic nervous system. Several nerve blocks have a marked effect on autonomic nervous activity. Furthermore, stellate ganglion block changes cardiac autonomic nervous activity. Thus, CPB could influence the sympathetic activity of the cardiac plexus. The aim of the present study was to see whether CPB modulated heart rate variability (HRV) in patients with pancreatic cancer. METHODS: Twelve patients received neurolytic CPB using 14 ml absolute alcohol. Data recorded in a palm-sized electrocardiographic unit were analyzed for HRV. RESULTS: CPB using a neurolytic solution did not induce any significant changes in the low-frequency (LF)/high-frequency (HF) ratio of HRV (LF/HF, P = 0.4642). Furthermore, the procedure did not induce any significant changes in blood pressure (systolic, P = 0.5051; diastolic, P = 0.5180). CONCLUSION: CPB did not induce any significant changes in HRV or hemodynamics.

Genomic characteristics of listeria monocytogenes causing invasive listeriosis in Japan.

We reviewed 18 listeriosis cases in Japan and performed molecular analysis of causative Listeria monocytogenes (LM) isolates. Strains genetically related to those from other countries caused various types of listeriosis, including vascular listeriosis in immunocompetent elderly people. Our results highlight the importance of integrated clinical and genomic analysis of LM.

Changes in cardiovascular parameters in rats exposed to chronic widespread mechanical allodynia induced by hind limb cast immobilization.

To elucidate the relationship between chronic pain conditions with cast immobilization and autonomic function, we investigated the functional changes of the autonomic nervous system in conscious rats with chronic post-cast pain (CPCP) induced by a two-week cast immobilization of one hind limb. We telemetrically examined the time courses of systolic arterial blood pressure (SBP), heart rate (HR), and the middle-frequency (MF) component obtained from the power spectral analysis of SBP variability as a vasomotor sympathetic index. We also investigated the baroreflex sensitivity to phentolamine, an α-adrenoceptor antagonist, and the SBP and HR responses to a low ambient temperature (LT; 9.0 ± 0.2°C) exposure, a sympathetic stimulant. Rats exposed to cast immobilization exhibited mechanical allodynia lasting for at least 10 weeks after cast removal in the calf area (skin and muscle) of the bilateral hind limbs. Under resting conditions, the SBP, HR, and MF components were significantly increased during cast immobilization (all p < 0.001). Following cast removal, these parameters gradually decreased and within 1 week reached lower than baseline levels, lasting for over 10 weeks. Phentolamine administration (10 mg/kg, intraperitoneally) significantly decreased the SBP before and during cast immobilization (before, p < 0.001; during, p = 0.001) but did not lower the SBP after cast removal. The baroreflex gain after phentolamine administration, calculated as the HR increase divided by the SBP reduction, was significantly increased after cast removal (p = 0.002). The SBP increase on LT exposure was significantly greater after cast removal than that before cast immobilization, suggesting hypersensitivity to sympathetic neurotransmitters. These results revealed that, in the CPCP model, sympathetic activation was augmented during cast immobilization, which then decreased after cast removal and remained below normal levels with persisting pain behaviors. Additionally, the responsiveness of the autonomic nervous system was impaired in the CPCP model.

Tapentadol Safety and Patient Characteristics Associated with Treatment Discontinuation in Cancer Therapy: A Retrospective Multicentre Study in Japan.

INTRODUCTION: Tapentadol has analgesic effects comparable to those of conventional opioids and is associated with fewer side effects, including gastrointestinal symptoms, drowsiness, and dizziness, than other opioids. However, the safety of tapentadol in the Japanese population remains unclear; the present multicentre study aimed to examine the safety of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events. METHODS: The safety of tapentadol was assessed retrospectively in patients with any type of cancer treated between August 18, 2014 and October 31, 2019 across nine institutions in Japan. Patients were examined at baseline and at the time of opioid discontinuation. Multivariate analysis was performed to identify factors associated with tapentadol discontinuation owing to adverse events. RESULTS: A total of 906 patients were included in this study, and 685 (75.6%) cases were followed up until tapentadol cessation for any reason. Among patients who discontinued treatment, 119 (17.4%) did so because of adverse events. Among adverse events associated with difficulty in taking medication, nausea was the most common cause of treatment discontinuation (4.7%), followed by drowsiness (1.8%). Multivariate analysis showed that those who were prescribed tapentadol by a palliative care physician (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.99, p = 0.004), patients switching to tapentadol due to side effects from previous opioids (OR 2.19, 95% CI 1.05-4.56, p = 0.037), and patients who did not use naldemedine (OR 5.06, 95% CI 2.47-10.37, p < 0.0001) had an increased risk of treatment discontinuation owing to adverse events. CONCLUSIONS: This study presents the safety profile of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events in the Japanese population. Prospective controlled trials are required to evaluate the safety of tapentadol and validate the present findings. TRIAL REGISTRATION NUMBER: UMIN 000044282 (University Hospital Medical Information Network).

Multidrug-resistant Gram-negative Bacterial Bloodstream Infections in Children's Hospitals in Japan, 2010-2017.

BACKGROUND: The risk factors of multidrug-resistant (MDR) Gram-negative bacilli (GNB) bloodstream infection (BSI) are not yet known in children. Our aim was to evaluate risk factors and outcomes associated with MDR GNB BSI in children. METHODS: Patients with GNB BSI were enrolled between April 2010 and March 2017 at 8 children's hospitals in Japan. Clinical and microbiologic data were collected retrospectively. The risk factors and outcomes of MDR and non-MDR GNB BSI were compared. RESULTS: In total, 629 GNB BSI episodes met the case definition. The median age and proportion of males were 2 years (interquartile range, 0.3-8.7) and 50.7%, respectively. An underlying disease was found in 94% of patients. The proportion of BSI cases that developed >48 hours after admission was 76.2%. MDR comprised 24.5% of BSI cases. The MDR rate did not change over time (P = 0.540). The effective coverage rate of the initial empiric therapy for the MDR and non-MDR BSI cases was 60.4% and 83.4%, respectively (P < 0.001). The all-cause mortality rate at 28 days for all BSI, MDR-BSI and non-MDR BSI cases was 10.7%, 13.6% and 9.7%, respectively (P = 0.167). MDR BSI was independently associated with cancer chemotherapy within 30 days (odds ratio [OR] 43.90), older age (OR 1.05) and admission to the neonatal ward (OR 0.019). CONCLUSIONS: One-fourth of GNB BSI cases were MDR. Cancer chemotherapy and older age were risk factors for MDR GNB BSI in children's hospitals. MDR did not increase the all-cause mortality rate.

A Multicenter Cohort Study to Explore Differentiating Factors between Tumor Fever and Infection among Advanced Cancer Patients.

Background: Tumor fever and infection are common febrile etiologies among advanced cancer patients. To date, only few studies have been conducted to differentiate between tumor fever and infections. Objective: This study aimed to identify discriminating factors that provide rapid results and are feasible and minimally invasive for discriminating between tumor fever and infection in advanced cancer patients. Methods: This is a retrospective cohort study. Advanced cancer patients with clinically diagnosed tumor fever or infection, who received medical treatment from palliative care specialists in 10 nationwide Japanese hospitals, were consecutively identified during August 2012 and November 2014. The symptoms, physical findings, blood test results at baseline and during fever, imaging findings, and sociodemographic factors of these patients were retrospectively extracted. Results: Thirty-three patients with tumor fever and 72 patients with infection were identified. Their mean age was 68.8 years, 68 (64.8%) were men, and the median palliative performance status (PPS) was 50. Statistically significant factors predicting tumor fever by logistic regression analysis were as follows: deterioration of PPS (odds ratio, 0.078), shaking chills during fever (0.067), and change from baseline data of neutrophil/lymphocyte ratio of ≥5 (0.14). Conclusions: Shaking chills during fever, and changes from baseline of performance status and white blood cell differentiation can be useful to differentiate between tumor fever and infection among advanced cancer patients. Further confirmatory studies are needed.

Oxygen-flask combustion with light beam ignition.

A robust oxygen-flask combustion system was developed using light beam ignition. An appropriate amount of environmental sample was wrapped with a small piece of filter paper and held in a basket made of platinum-zirconium spiral. After the sample was inserted into an oxygen-filled flask containing an acid mixture, the light beam from an overhead projector lamp was focused to ignite the sample. The combusted products were absorbed into the acid mixture by shaking the flask and then used for the ICP-AES measurement of metals. The proposed method was successfully applied to the determination of metals in Environmental Standard Reference Materials and Artemia salina. The present method is also applicable to ion chromatographic measurements of chlorine in polyvinyl chloride wall paper by using hydrogen peroxide as absorbent.