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This study aimed to determine whether sleep disturbance, defined as the wakeup frequency at night, is associated with atherogenic dyslipidemia and to explore possible sex differences.A total of 1,368 adults aged 19-70 years were included in the study of lifestyles and atherogenic dyslipidemia at the National Taiwan University Hospital in the period of 2008-2012. They completed a questionnaire regarding lifestyle information and sleep quality, including sleep hour duration, use of sleeping pills, and wakeup frequency during nighttime sleep. The measured lipid profiles included total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and small dense LDL-C (sdLDL-C). Multivariate logistic regression was performed to determine habitual interrupted sleep and the odds ratio of atherogenic dyslipidemia following adjustment for conventional risk factors and for sex-based subgroup analysis.A wakeup frequency ≥ 3 times per night was independently associated with an increased risk [odds ratio (95% confidence interval)] of dyslipidemia was 1.96 (1.17-3.28), and non-HDL-C ≥ 160 mg/dL was 1.78 (1.09-2.89). A higher wakeup frequency was associated with increased atherogenic dyslipidemia in women than in men. The multivariate adjusted relative risks for non-HDL ≥ 160 mg/dL and cholesterol ≥ 200 mg/dL were 3.05 (1.27-7.34) and 4.01(1.29-12.45) for female individuals with insomnia and those with a wakeup frequency ≥ 2 times per night, respectively.A higher wakeup frequency was associated with atherogenic dyslipidemia in Taiwanese adults, particularly in women. This study also provided another evidence of increasing cardiovascular diseases in subjects with habitual interrupted sleep.

SUMMARY Background Multidrug-resistant (MDR) gram-negative bacterial (GNB) infections remain a significant cause of morbidity and mortality among surgical patients. The objective of our study was to recognize the risk factors for MDR GNB infection in patients with abdominal surgery and determine the predictors independently associated with death. Methods From 2010 to 2017, a retrospective cohort study was conducted among patients with abdominal surgery admitted in surgical intensive care unit (ICU). Patients with GNB infections were included for analyses. Results A total of 364 patients with abdominal surgery experienced GNB infections, among them, 117 (32.1%) were MDR GNB infection. Of 133 MDR GNB isolates, the most frequent isolate was Escherichia coli (45.1%). Patients with MDR GNB infection had significantly longer ventilator days and hospital stay, as well as higher 30-day and in-hospital mortality compared to non-MDR GNB patients. Multivariable analysis showed longer length of pre-ICU stay, surgical re-exploration, receipt of group 2 carbapenems (e.g. imipenem, meropenem and doripenem) and fluoroquinolones, and higher total bilirubin were independent risk factors for the acquisition of MDR GNB infection. Predictors for 30-day mortality among patients with MDR GNB infection were chronic kidney disease, receipt of group 2 carbapenems and inappropriate empirical antimicrobial therapy. Conclusions This study provides important information about the risk factors for subsequent MDR GNB infection and 30-day mortality among the patients with abdominal surgery.

The structural impact of chronic pain on amygdala in chronic pain (CP) patients remains unclear, although major depression and anxiety are known to be associated with its increase and decrease in size, respectively. This study aimed at examining the relationship between emotional stress and amygdala size in CP patients. The effects of mediating and moderating variables were also examined. The PubMed, Embase, and Web of Science databases were searched for English clinical trials from inception to February 2022 using the appropriate keyword strings. We compared the differences in amygdala size assessed with magnetic resonance imaging between CP patients with emotional stress and healthy counterparts. Of the 49 full-text articles identified, 13 studies enrolling 1,551 participants including 738 CP patients with emotional stress and 813 controls were analyzed. Emotional stress evaluated with questionnaires based on Beck depression inventory, Hamilton depression/anxiety scale, state-trait anxiety inventory, and hospital anxiety and depression scale revealed significant differences between CP patients with emotional stress and controls, indicating a subclinical but significant level of emotional stress in CP patients. The results demonstrated an amygdala shrinkage among CP patients with emotional stress compared to the controls, especially the right side (P = .02). Besides, pain from a single body region was more likely to impact the amygdala size compared to diffuse pain (P = .02). Regression analysis revealed no significant association between continuous variables (age, gender, pain duration/intensity) and amygdala size. Our findings demonstrated that emotional stress was associated with a reduced right amygdala size in CP patients.

Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear.The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, β-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo.Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/β-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma.Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.

Dendritic cells (DCs) are professional antigen presenting cells that play a critical role in bridging innate and adaptive immunity. Numerous studies have shown that tobacco constituents present in conventional cigarettes affect the phenotype and function of DCs; however, no studies have examined the effects of vapour from E-cigarettes on human DCs. Here, the effects of E-cigarette vapour extract (ECVE) on the phenotype and function of DCs were investigated by creating an in vitro cell culture model using human monocyte-derived DCs (MoDCs). Immature DCs were generated from peripheral blood monocytes and mature DCs were then produced by treatment with LPS or Poly I:C for 24 h. For LPS-matured DCs, 3% ECVE treatment slightly suppressed HLA-DR and CD86 expression, whereas 1% ECVE treatment enhanced IL-6 production. The overall expression of 29 signalling molecules and other cytoplasmic proteins (mainly associated with DC activation) was significantly upregulated in immature DCs by 1% ECVE, and in LPS-treated DCs by 3% ECVE. In particular, the condition that induced IL-6 production also upregulated MAPK pathway activation. These findings indicate that E-cigarette vapour moderately affects human DCs, but the effects are less pronounced than those reported for tobacco smoke. Electronic supplementary material The online version of this article (10.1007/s00204-020-02757-8) contains supplementary material, which is available to authorized users.

© 2019 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Electronic cigarettes (E-cigarettes) are considered a preferable alternative to conventional cigarettes due to the lack of combustion and the absence of tobacco-specific toxicants. E-cigarettes have rapidly gained in popularity in recent years amongst both existing smokers and previous non-smokers. However, a growing literature demonstrates that E-cigarettes are not as safe as generally believed. Here, we discuss the immunological, and other, deleterious effects of E-cigarettes on a variety of cell types and host defence mechanisms in humans and in murine models. We review not only the effects of complete E-cigarette liquids, but also each of the main components—nicotine, humectants and flavourings. This MiniReview thus highlights the possible role of E-cigarettes in the pathogenesis of disease and raises awareness of the potential harm that E-cigarettes may cause.

Background: Multidrug-resistant (MDR) gram-negative bacterial (GNB) infections remain a significant cause of morbidity and mortality among surgical patients. The objective of our study was to recognize the risk factors for MDR GNB infection in surgical intensive care unit (SICU) patients with abdominal surgery and determine the predictors independently associated with death.Methods: From 2010 to 2017, a retrospective cohort study was conducted among patients with abdominal surgery admitted in SICU. Patients with GNB (MDR and non-MDR) infections were included for analyses. Results: A total of 364 patients with abdominal surgery experienced GNB infections, among them, 117 (32.1%) were MDR GNB infections. Of 133 MDR GNB isolates, the most frequent isolate was Escherichia coli (45.1%). Patients with MDR GNB infection had significantly longer ventilator days and hospital stay, as well as higher 30-day and in-hospital mortality compared to non-MDR GNB patients. Multivariable analysis showed longer length of pre-ICU stay, surgical re-exploration, received anti-pseudo carbapenems and fluoroquinolones, and higher total bilirubin were independent risk factors for the acquisition of MDR GNB infection. Predictors for 30-day mortality among patients with MDR GNB infection were chronic kidney disease, received anti-pseudo carbapenems and inappropriate empirical antimicrobial therapy.Conclusions: This study provides important information about the risk factors for subsequent MDR GNB infection and 30-day mortality among the patients with abdominal surgery. Given the increasingly MDR GNB infection and mortality, implementation of antimicrobial stewardship programs in critical care unit is crucial to reduce MDR pathogens and optimize antimicrobial therapies.

Background: The prevalence of vancomycin-resistant enterococci (VRE) is increasing among liver transplant recipients. This study aimed to explore the clinical features of liver transplant recipients with VRE infection/colonization and to determine the impact of daptomycin dosage on the outcomes. Methods: We retrospectively enrolled pre-transplant and post-transplant patients with VRE colonization/infection from 2016 to 2019. Results: Altogether, 428 patients underwent liver transplantation. Among these, 22 (5.1%) patients developed VRE colonization/infection. All VRE isolates were Enterococcus faecium. Two (9%) patients acquired VRE in the pre-transplant period, 16 (3 colonizations and 13 infections) (72.7%) in the early post-liver transplant period (≤60-day after transplantation), and 4 (2 colonization and 2 infections) (18.1%) in the late post-liver transplant period (>6-month after transplantation). Among 13 patients with early post-liver transplant VRE infection, 12 (92.3%) underwent living-donor liver transplantation and 1 underwent deceased donor liver transplantation. Among these 13 patients, the median time from transplant to emergence of VRE infection was 12 days. The median interval from VRE infection to death was 27 days and the 30-day mortality was 67%. Of these 13 patients, eleven patients (8 survived; 3 died) received daptomycin therapy for VRE. Among them, 4 (36.3%) received daptomycin doses Conclusions: In summary, the suboptimal dosage of daptomycin may have contributed to a higher rate of in-hospital mortality. Doses ≥8 mg/kg may be needed to adequately treat VRE infection in early post-liver transplant recipients.Level of evidence: Level III

Additional file 2: Supplement Table 1. List of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia who received continuous teicoplanin treatment.

Background: Many studies have shown that vancomycin is inferior to β-lactam antibiotics in terms of effectiveness in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. However, limited data are available regarding the comparison of clinical outcomes between patients receiving initial teicoplanin and those receiving β-lactam antibiotics for MSSA bacteremia.Methods: Eighty-four adults with MSSA bacteremia were included: initial teicoplanin treatment group (n=28) and β-lactam treatment group (n=56). The two groups were further stratified based on propensity score matching according to the outcome analysis using a logistic regression model. We investigated the clinical outcomes between the groups before and after propensity score matching after treatment completion.Results: Pittsburgh bacteremia score ≥4 (odds ratio, 60.6; 95%CI, 7.4–496.8) was an independent risk factor for unfavorable outcome. After propensity score matching, the initial teicoplanin treatment group and the β-lactam treatment group consisted of 28 patients each. No statistically significant differences were observed in the proportions of patients with favorable outcomes and 30-day overall mortality rates between the groups before and after propensity score matching after the completion of teicoplanin or β-lactam treatment. The Kaplan-Meier 30-day survival curve also showed no significant difference between the patients receiving initial teicoplanin treatment and those receiving β-lactam treatment before and after matching (hazard ratio, 1.84, 95%CI, 0.60–5.64; and 3.12, 95%CI, 0.98–9.99, respectively).Conclusions: There were no significant difference in clinical outcomes between initial teicoplanin treatment and β-lactam treatment among patients with MSSA bacteremia. Pittsburgh bacteremia score ≥4 was a significant risk factor for mortality.

Ching-Yen Tsai,1 Chen-Hsiang Lee,1,2 I-Ling Chen3 1Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2College of Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Background: Recent reports have described decreased effectiveness of teicoplanin in the treatment of bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) with teicoplanin minimal inhibitory concentration (MIC)≥1.5 mg/L. Consensus guidelines recommend considering use of alternative agents for MRSA infections involving a higher teicoplanin MIC, despite of limited data to support this recommendation. Patients and methods: To compare the clinical outcome among patients with bacteremia due to MRSA with teicoplanin MIC≥1.5 mg/L, we included patients who received high-dose daptomycin (≥8 mg/kg/day) and those who received standard-dose (6 mg/kg/day) or high-dose (6 mg/kg/12 hours) maintenance teicoplanin. The primary endpoint was a favorable outcome, defined as the resolution of clinical signs and symptoms and a negative culture report at the end of therapy. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Results: Of 142 patients eligible for inclusion, 28 (19.7%) were treated with high-dose daptomycin, 27 (19.0%) with high-dose teicoplanin, and 87 (61.3%) with standard-dose teicoplanin. In multivariate regression analysis, Pittsburgh bacteremia score≥4 (OR, 5.3; 95% CI, 1.9–14.5) was independently associated with an unfavorable outcome. After propensity-score matching with age and Pittsburgh bacteremia score≥4, patients on high-dose daptomycin were more likely to have favorable outcomes than those on standard-dose teicoplanin (74.1%vs 42.6%; P=0.02). However, there was no significant difference in terms of favorable outcomes (P=0.12) between patients receiving high-dose daptomycin and those receiving high-dose teicoplanin after the same propensity-score matching. Conclusion: Treatment with high-dose daptomycin resulted in significantly better outcomes than with standard-dose teicoplanin in the treatment of MRSA bacteremia with teicoplanin MIC≥1.5 mg/L. However, the clinical outcome of the patients receiving high-dose teicoplanin was similar to that of the patients receiving high-dose daptomycin. Keywords: gram-positive bacteria, antimicrobial susceptibility, pharmacodynamics, glycopeptide, lipopeptide

Objective Platelets catalyze the development of hyperinflammation and microthrombosis and contribute to increases in accumulation of circulating platelet-leukocyte complex, the key event in the development of disseminated infection. Subjects and methods To determine the relationships of platelet activity in diabetic patients with invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS), a total of 175 diabetic patients with community-acquired Klebsiella pneumoniae (KP) bacteremia were included in this study. We compared the platelet reactivity of 40 patients with IKLAS, 40 patients with non-IKLAS, and eight healthy controls using a whole-blood flow cytometry-based assay. Results Patients who were infected with strains expressing K1/K2 serotype (adjusted odds ratio [AOR], 8.81; 95% CI, 2.18-35.53) and those with HbA1c ≥9% (AOR, 4.97; 95% CI, 1.73-14.23) were more likely to present with IKLAS, whereas those who had recent therapy with aspirin (AOR, 0.17; 95% CI, 0.04-0.79) were less likely to present with IKLAS. Among patients with IKLAS, patients with a poor glycemic control were more likely to present with hepatic venous thrombo-phlebitis than those with suboptimal or good glycemic control (P=0.03). Patients with IKLAS had a higher median fluorescence intensity of the platelet membrane expression of P-selectin than those with non-IKLAS (78.0 vs 28.0, P

Objectives Teicoplanin, a glycopeptide, is regarded as among the drug choices for methicillin-resistant Staphylococcus aureus (MRSA) infections. Few studies have evaluated the relationship between teicoplanin minimal inhibitory concentrations (MICs) and outcomes among patients with serious MRSA infections. Subjects and methods We investigated the relationship between teicoplanin maintenance dose and clinical outcomes, on the completion of teicoplanin therapy, in bacteremia patients with MRSA infection, with different teicoplanin MICs. A total of 146 adult patients with MRSA bacteremia were enrolled at Kaohsiung Chang Gung Memorial Hospital between September 2012 and September 2015. Results A higher number of patients in the high-dose regimen group (6 mg/kg/12 h) had favorable outcomes than those in the standard-dose regimen group (6 mg/kg/24 h) (84.1% vs 41.2%; p

Orthopedic surgeons often face a clinical dilemma on how to manage antiplatelet therapies during the time of surgery. This retrospective study is aimed to investigate the bleeding risk and adverse events in patients who hold or keep clopidogrel during elective major joints arthroplasty. Two hundred and ninety-six patients that were treated with clopidogrel while undergoing total hip or knee joint replacement between January 2009 and December 2018 were studied. Group 1 included 56 patients (18.9%) who kept using clopidogrel preoperatively. Group 2 included 240 patients who hold clopidogrel use ≥5 days preoperatively. Blood transfusion rates, estimated blood loss, complication rates, and adverse cardiocerebral events were collected and analyzed. The mean total blood loss was more in the group 1 patients as compared with that in the group 2 patients (1212.3 mL (685.8 to 2811.8) vs. 1068.9 mL (495.6 to 3294.3), p = 0.03). However, there was no significant difference between the two groups of patients regarding transfusion rates, bleeding-related complications, and infection rates. There was a trend toward a higher incidence of adverse cardiocerebral events in patients withholding clopidogrel for more than 5 days before surgery. The results of this study suggest that clopidogrel continuation could be safe and advisable for patients at thrombotic risk undergoing primary major joint replacement. Acute antiplatelet withdrawal for an extended period of time might be associated with an increased risk of postoperative thromboembolic events. More studies are required in the future to further prove this suggestion.

I-Ling Chen,1,2 Chen-Hsiang Lee,2–4 Shih-Wen Ting,2,3 Lily Yu-Chin Wang1 1Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Infection Control Team, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 4College of Medicine, Chang Gung University, Kaohsiung, Taiwan Objectives: The increasing number of reports on infections due to carbapenem-resistant Gram-negative bacilli (GNB) has raised concerns, because they have complicated empiric or guided antibiotic therapy for critically ill patients. We aimed to develop a scoring system to predict nosocomial imipenem-resistant GNB (IR-GNB) septicemia among the critically ill patients.Materials and methods: The study included critically ill adult patients with nosocomial GNB septicemia at Kaohsiung Chang Gung Memorial Hospital (CGMH) in 2013–2015, and the scoring system for predicting IR-GNB septicemia was developed, followed by prospective validation conducted among patients at Linkou CGMH and Kaohsiung CGMH between January and June, 2016.Results: In the development of the scoring system, 748 patients were included. The independent factors associated with IR-GNB septicemia were prior exposure (days) to carbapenems (adjusted odds ratio [aOR] per 1-day increase, 1.1; 1–3 days: 2 points, 4–6 days: 5 points, 7–9 days: 8 points, and ≥10 days: 13 points), use of mechanical ventilation (aOR 3.7; 5 points), prior colonization with IR-GNB strains (aOR 3.5; 5 points) within 30 days before the onset of GNB septicemia, and comorbid condition with chronic kidney disease (aOR 2.1; 3 points). The internal validation showed an area under the receiver operating characteristic curve (ROC) of 0.75; and an external validation among 314 patients showed similarly good performance (ROC 0.77). Youden’s index indicated the score of ≥6 as the best cutoff value with sensitivity of 75% and specificity of 79%.Conclusion: This scoring system might help clinicians stratify the risk for developing IR-GNB septicemia among critically ill patients and combined antibiotics may be used until antimicrobial de-escalation/adjustment is clearly indicated by the subsequently identified GNB and its susceptibility profile. Keywords: antimicrobial resistance, carbapenem, bacteremia, nosocomial infection, scoring system, outcome

Chen-Hsiang Lee,1,2 I-Ling Chen,3 Chia-Chin Li,4 Chun-Chih Chien4 1Department of Internal Medicine, Division of Infectious Diseases, Kaohsiung Chang Gung Memorial, Hospital, 2Chang Gung University, College of Medicine, 3Department of Pharmacy, 4Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Objectives: Cefotaxime-resistant Enterobacteriaceae (CE) infections are intractable, with limited treatment options. Though carbapenems are frequently prescribed for CE infections, the emergence of carbapenem-resistant Enterobacteriaceae is of huge concern. Flomoxef is effective against CE in vitro, and some clinical data on its demonstrated effectiveness against CE bloodstream infections (BSIs) exists.Patients and methods: We conducted a retrospective study on adults with BSI caused by flomoxef-susceptible CE to investigate the efficacy of flomoxef compared with that of ertapenem. The outcome was evaluated with propensity score-based matching and logistic regression analysis.Results: Demographic and clinical characteristics of patients treated with flomoxef (n = 58) or ertapenem (n = 188) were compared. In the multivariate analysis, severe sepsis (adjusted odds ratio [AOR] = 3.84; 95% confidence interval [CI], 1.16–12.78; p = 0.03), high BSI mortality score (AOR = 5.59; 95% CI, 2.37–13.21; p < 0.01), ultimately or rapidly fatal comorbidity (AOR = 10.60; 95% CI, 3.43–32.75; p < 0.01), and pneumonia (AOR = 10.11; 95% CI, 3.43–29.81; p < 0.01) were independently associated with 28-day mortality. Using propensity scores, 58 flomoxef-treated patients were matched to 116 ertapenem-treated patients. There were no intergroup differences in BSI severity, comorbidity, or BSI sources. The 28-day mortality rates (20.7% vs 13.8%, p = 0.28) did not differ significantly. However, hospitalization length was shorter in the ertapenem group (10.2 ± 8.5 vs. 14.6 ± 9.4 days, p < 0.01).Conclusion: Although similar outcomes were observed between the groups, ertapenem therapy was associated with a shorter hospitalization time in adults after CE BSI. Keywords: bacteremia, cephamycin, ESBL, flomoxef, outcomes, MIC

Background/purpose: The long-term effects of antimicrobial-stewardship programs in the intensive care units (ICUs) have not been adequately examined. We evaluated the impact of an online comprehensive antimicrobial stewardship program (OCASP) on the outcomes of patients in 200-bed medical/surgical ICUs over the course of 11 years. Methods: We analyzed the records of adult patients admitted to ICUs during the 5 years before (n = 27,499) and the 6 years after (n = 33,834) implementation of an OCASP. Antimicrobial consumption, expenditures, duration of treatment, incidence of healthcare-associated infections (HAIs), prevalence of HAIs caused by antimicrobial-resistant strains, and crude or sepsis-related mortality of patients were analyzed. Segmented regression analyses of interrupted time series were used to assess the significance of changes in antimicrobial use. Results: Compared to the patients in the pre-OCASP period, the patients in the post-OCASP period were older, had greater disease severity, longer ICU stays, and were more likely to receive antimicrobials, but had lower antimicrobial expenditures and crude and sepsis-related mortality. The trend of overall antimicrobial use [slope of defined daily dose/1000 patient-days vs. time) increased significantly before OCASP implementation (p

This paper distinguishes between the concepts of socio-cognitive mindfulness applied in a number of tourism studies and meditative mindfulness derived from a Buddhist philosophy. An operational definition of meditative mindful tourist experiences is proposed based on forty-three semi-structured interviews involving 77 episodes of meditative mindful experiences. The paper also proposes a framework of meditative mindfulness in tourism. The framework identifies a number of antecedents to meditative mindful experience episodes and reveals several psychological and physical benefits including mental ease and response flexibility. This is the first paper to examine meditative mindful tourist experiences in tourism contexts and to explore their antecedents and consequences.

We report a case of hypersensitivity pneumonitis (HP) in a young person secondary to vaping. He presented with a putative diagnosis of asthma and required extracorporeal membrane oxygenationbecause of intractable respiratory failure. He developed a critical illness and steroid myopathy and required prolonged rehabilitation. Our patient fulfils diagnostic criteria for HP secondary to e-cigarettes with a positive exposure history, deterioration after skin prick testing, specific serum IgM antibodies against the implicated liquid raising the possibility that the relevant antigen was present in that liquid and radiological and histopathological features compatible with acute HP. There are two learning points. The first is always to consider a reaction to e-cigarettes in someone presenting with an atypical respiratory illness. The second is that we consider e-cigarettes as ‘much safer than tobacco’ at our peril.

The associations between nutritional markers and heart rate variability (HRV) are poorly addressed. This study aimed to evaluate whether malnutrition is associated with the altered autonomic nervous system (ANS) function. This cross-sectional study was conducted enrolling 175 patients (100 women, mean age 65.1 ± 12.9 years) receiving chronic hemodialysis in a teaching hospital from June to August 2010. We performed HRV measurements before and during the index hemodialysis and compared these HRV values between two groups categorized by the individual nutritional marker. By using the multivariate generalized estimating equation with adjustment, we exhibited the independent associations between HRV and poor nutritional status defined by serum albumin &lt, 3.8 g/dL, total cholesterol &lt, 100 mg/dL, body mass index &lt, 23 kg/m2, bodyweight loss within six months &gt, 10%, bodyweight loss within three months &gt, 5%, and normalized protein catabolic rate &lt, 1.1 g/kg BW/day. The current study disclosed ANS impairment in hemodialysis patients with poor nutritional status. The impaired ANS function might be a potential mechanism linking malnutrition to subsequent adverse prognoses in hemodialysis patients. Further investigations are warranted to confirm these findings and clarify the causal association among this complex issue.

Chen-Hsiang Lee,1 I-Ling Chen,2 Chia-Chin Li,3 Chun-Chih Chien31Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanBackground: Flomoxef is potentially effective against β-lactamase-producing Enterobacteriaceae because limited clinical data demonstrate its effectiveness against Enterobacteriaceae bloodstream infections (BSIs) based on its minimum inhibitory concentrations (MICs). This study was conducted to determine the optimal breakpoints based on the survival of patients with Enterobacteriaceae BSIs treated with flomoxef.Methods: The 30-day crude mortality rate was analyzed among 224 adults who initiated flomoxef monotherapy for Enterobacteriaceae BSIs at a medical center over a 3-year period, according to the flomoxef MICs of the initial isolates. The outcome was evaluated by classification and regression tree modeling and by logistic regression analysis.Results: The 30-day crude mortality was approximately two fold greater in patients whose isolates had flomoxef MICs of ≥2 mg/L (54.9% [62/113]) than in those with isolates with MICs of ≤1 mg/L (26.1% [29/111]); the differences were significant in bivariate analysis (P

BACKGROUND Our previous study demonstrated that pediatricians prescribe antibiotics without proper clinical justification to patients with enterovirus infection, although antibiotics are not effective in treating the infections caused by these viruses. To improve the quality of healthcare, we aim to evaluate the association of clinical and demographic characteristics of patients and further to identify the determining factors for prescribing antibiotics to children experiencing enterovirus infection. METHODS We retrospectively reviewed the medical records of children who were hospitalized between January 2008 and December 2016 with a diagnosis of herpangina or hand-foot-mouth disease (HFMD). We identified those children who were prescribed antibiotics for at least 24 hours during admission. We conducted a retrospective descriptive study to analyze data in order to determine the factors associated with pediatrician antibiotics prescribing for enterovirus infection. RESULTS In the nine years of study period, the rate of antibiotics use was about 13% in these patients. A total of 3659 patients were enrolled during 2008~2012 and analyzed in detail. Elevated levels of C-reactive protein (CRP) and presence of leukocytosis in blood (WBC) were both significantly associated with pediatrician antibiotic prescribing for enterovirus infection (p

SummaryBackgroundEnteroviruses are seasonally prevalent each year in Southeast Asia. Elevated C-reactive protein (CRP) levels have been noted in minor populations of patients, and antibiotics may be prescribed under the impression of a suspected bacterial infection. This prescription might be inappropriate, resulting in further bacterial resistance and medical expense. The aim of this study was to delineate how effective antibiotics are for children suffering from enterovirus infection complicated with a high CRP level.MethodsThe medical records of children hospitalized between January 2008 and December 2012 with herpangina or hand, foot and mouth disease were reviewed retrospectively. The children enrolled were divided into three groups, A, B, and C, by CRP level, which were

This work investigates the electrochemical activity and durability of bimetallic Pt–Co electrocatalysts on carbon nanotube (CNT) electrodes, which are prepared by using a microwave-assisted polyol process within a short period of ∼6 min. Multilayered CNTs are directly grown on carbon paper (CP) substrate by catalytic chemical vapor deposition with Ni catalyzing the growth of CNTs. The as-grown CNTs are employed as the support for the subsequent Pt–Co catalysts, which are deposited on the CNTs by using one- and two-step microwave-assisted reduction processes. Physicochemical characterizations are conducted to identify particle dispersion, particle-size distribution, and Pt/Co atomic ratio in the binary catalysts. It has been shown that Pt–Co–CNT/CP electrocatalyst, prepared by two-step microwave heating (i.e., deposition of Pt, followed by Co addition), offers highly electrochemical surface area and stable activity during potential cycling (1000 cycles). Such Pt–Co crystallographic phases on CNT-based support are found to be more corrosion-resistant in acidic electrolyte and represent the preferred phase structure under the consideration of activity stability. The fact that the microwave-assisted deposition of Pt–Co catalysts promotes electrochemical activity and stability has a great advancement on the development of binary electrocatalysts for fuel-cell applications.

Aeginetia indicaLinn. (Guan-Jen-Huang, GJH), a traditional Chinese herb, has the potential to be an immunomodulatory agent. The purpose of this study was to explore the effect of GJH in the treatment of renal cancer. Concentration-effect curves for the influence of GJH on cellular proliferation showed a biphasic shape. Besides, GJH had a synergistic effect on cytotoxicity when combined with 5-fluorouracil (5-FU)which may be due to the alternation of the chemotherapeutic agent resistance-related genes and due to the synergistic effects on apoptosis. In addition, treatment with GJH extract markedly reduced 786-O cell adherence to human umbilical vein endothelial cells (HUVECs) and decreased 786-O cell migration and invasion. In a xenograft animal model, GJH extract had an inhibitory effect on tumor cell-induced metastasis. Moreover, western blot analysis showed that the expression of intercellular adhesion molecule-1 (ICAM-1) in 786-O cells was significantly decreased by treatment with GJH extract through inactivation of nuclear factor-κB (NF--κB). These results suggest that GJH extract has a synergistic effect on apoptosis induced by chemotherapeutic agents and an inhibitory effect on cell adhesion, migration, and invasion, providing evidence for the use of water-based extracts of GJH as novel alternative therapeutic agents in the treatment of human renal cancer.

Both uremia and metabolic syndrome (MetS) affect heart rate variability (HRV) which is a risk factor of poor prognoses. The aim of this study was to evaluate the impact of MetS on HRV among chronic hemodialysis patients. This cross-sectional study was carried out in a teaching hospital in Northern Taiwan from June to August, 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled. HRV were measured for 4 times on the index hemodialysis day (HRV-0, -1, -2, and -3 at before, initial, middle, and late phases of hemodialysis, respectively), and the baseline demographic data and clinical parameters during the hemodialysis session were documented. Then we evaluated the impacts of MetS and its five components on HRV. One hundred and seventy-five patients (100 women, mean age 65.1 ± 12.9 years) were enrolled and included those with MetS (n = 91, 52 %) and without MetS (n = 84, 48 %). The patients with MetS(+) had significantly lower very low frequency, total power, and variance in HRV-0, total power and variance in HRV-2, and variance in HRV-3. (all p ≦ 0.05) When using the individual components of MetS to evaluate the impacts on HRV indices, the fasting plasma glucose (FPG) criterion significantly affected most indices of HRV while other four components including “waist circumference”, “triglycerides”, “blood pressure”, and “high-density lipoprotein” criteria exhibited little impacts on HRV. FPG criterion carried the most powerful influence on cardiac ANS, which was even higher than that of MetS. The HRV of patients with FPG(+) increased initially during the hemodialysis, but turned to decrease dramatically at the late phase of hemodialysis. The impact of FPG(+) outstood the influence of uremic autonomic dysfunction, and FPG criterion was the most important one among all the components of MetS to influence HRV. These results underscored the importance of interpretation and management for abnormal glucose metabolism.

Stress in everyday life is common in our postmodern society leading some people to seek relief and fulfilment from a range of leisure and lifestyle activities such as travel experiences. Travel in itself, even adventurous or unstructured travel does not guarantee that travellers will receive positive benefits from their experiences. However, the notion of mindfulness may play an important role in producing positive consequences from different experiences. Thus, this study explores the nature and experiential benefits of ‘meditative mindful’ tourist experiences that can be experienced during travel. Mindfulness is a mental state that may facilitate positive experiences. Understanding the importance of mindfulness is becoming a mainstream field of academic study in many therapeutic settings. However, there has been little discussion of mindfulness theory as it might be applied to tourism studies. Previous research in tourism has mainly focused on socio-cognitive mindfulness related to visitor learning rather than meditative mindfulness experiences. These include contexts such as tourist-wildlife encounters, appreciation of scenery, or through interaction with other people. The conceptual framework in this thesis is based on the Eastern notion of meditative mindfulness and has been used in Western therapeutic studies. In the past decade, evidence of the effectiveness and application of meditative mindfulness has grown dramatically due to a developing dialogue between Buddhist traditions and Western clinical psychology. There is a growing interest in whether meditative mindful experiences can occur outside of formal therapeutic settings, including travel. However, it is not clear how meditative mindful tourism experiences might be defined or whether they occur at all during travel. Furthermore, few studies have investigated the antecedents and consequences of meditative mindful experiences in tourism contexts. This thesis presents an exploratory study of the occurrence as well as the antecedents and consequences of the meditative mindfulness phenomenon in a tourism context. A qualitative methodology based on an interpretive constructivist paradigm was adopted for the data collection. Taiwanese backpackers in Australia were selected as respondents and snowball sampling was used to recruit participants. In total, 43 semi-structured interviews were completed, and a total of 77 instances of meditative mindful experiences were identified. The semi-structured interviews were conducted in Brisbane (at backpacker hostels) and at Uluru (Uluṟu-Kata Tjuṯa National Park), as these two main sites provided the best opportunities to meet Taiwanese backpackers. Two interview protocols were used in screening and extended interviews for qualifying and exploring the three research objectives. The interviews were transcribed and analysed using content analysis. NVivo 10 qualitative analysis software was used to increase the effectiveness and efficiency of the data analysis process. The findings indicated that meditative mindful experiences occurring in tourism contexts were characterised by three constructs of awareness (‘paying attention’, ‘living in the present’, and ‘non-elaborative awareness’). An operational definition of tourist experience associated with meditative mindfulness is proposed as “paying attention to a present moment experience, without elaboration on it”. In addition, the study clarified and contrasted three related concepts (meditative mindfulness, socio-cognitive mindfulness and flow). This thesis is the first study to empirically identify tourist experiences that have been associated with meditative mindfulness. The findings also identified the antecedents and consequences of meditative mindful tourist experiences. The four main types of identified triggers that facilitated tourists experiencing a mindful state were labelled as travel-induced relaxation, aesthetic appreciation, atmosphere of quietness, and curiosity-developing. Natural encounters and participation in specific activities were found to foster a state of being mindful. The mental process of meditative mindfulness contributes to relaxation and tranquillity and helps to create memorable experiences. Such psychological and physical benefits were identified among backpackers. A theoretical framework to provide a better understanding of the phenomenon and mental process of tourist meditative mindful experience is also discussed. This model is considered to be a useful tool for academics and the tourism industry to scope the mental and spiritual dimensions of tourist experiences for backpackers. An examination of how mindfulness occurs and how it can be further developed in tourism experiences is expected to be useful for tourism stakeholders. Business operators or policy makers should be aware of how to design engaging experiences and, in particular, how they can enhance affective, sensory or mental experiences through encouraging an awareness of the present moment and non-judgmental thinking during on-site visits. This may help tourism industries to better understand how to design holistic engaging experiences that benefit tourists’ understanding of an alternative access to personal fulfilment. A number of areas for further research are also discussed.