Effects of empiric antibiotic treatment based on hospital cumulative antibiograms in patients with bacteraemic sepsis: a retrospective cohort study.

OBJECTIVES: To assess the effects of empiric antibiotics with different degrees of appropriateness based on hospital cumulative antibiograms in patients with bacteraemic sepsis presenting to the emergency department (ED). METHODS: This retrospective cohort study included adult patients with sepsis and positive blood culture reports in the ED from February 2016 to December 2018. Based on isolated pathogens and empiric antibiotics which the patients received, these patients were divided into two groups using a cut-off of 70% for overall antimicrobial susceptibility (OAS) on hospital cumulative antibiograms 6 months prior to ED admission. Multivariate regression and sensitivity analyses were performed. RESULTS: In this study, 1055 patients were included. We used multivariate regression models which were adjusted for age, sex, co-morbidities, site of infection, organ dysfunction, and septic shock. Empiric antibiotics with OAS of ≥70% were associated with reduced in-hospital deaths (adjusted odds ratio, 0.46; 95% CI, 0.28-0.77) and 30-day mortality (adjusted odds ratio, 0.53; 95% CI, 0.33-0.86). They were more likely to result in a shortened length of intensive care unit stay by 1.60 days (95% CI, -3.00 to -0.20). CONCLUSIONS: Treatment with empiric antibiotics with OAS of ≥70% based on hospital cumulative antibiograms is associated with lower mortality and shorter length of intensive care unit stay in patients with bacteraemic sepsis in the ED.

Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2.

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.

Effects of enriched branched-chain amino acid supplementation on sarcopenia.

To evaluate the effects of short-term administration of enriched branched-chain amino acids (BCAAs) on subjects with pre-sarcopenia or sarcopenia, our quasi-experimental study enrolled 33 subjects (12 pre-sarcopenia/21 sarcopenia; 6 men/27 women; mean age 66.6 ± 10.3 years) to take one sachet (3.6 g) of enriched BCAA powder twice a day for five weeks followed by a discontinuation period of 12 weeks. We evaluated sarcopenic parameters, including grip strength, 6-meter gait speed, and bioelectrical-impedance-analysis-derived skeletal mass index (SMI), at baseline, 5 weeks, and 17 weeks. We found that both pre-sarcopenic and sarcopenic subjects showed improved SMI, gait speed, and grip strength at 5 weeks. However, all three parameters progressively declined at 17 weeks, especially SMI and grip strength in subjects aged < 65 years and gait speed and grip strength in subjects aged ≥ 65 years. It thus appears that supplementation with enriched BCAAs for 5 weeks correlates with short-term positive effects on sarcopenic parameters but attenuation of those effects following discontinuation for 12 weeks.

Diabetes Shared Care Program (DSCP) and risk of infection mortality: a nationwide cohort study using administrative claims data in Taiwan.

OBJECTIVE: The Diabetes Shared Care Program (DSCP) is an integrated care model in Taiwan that has been proven to improve the care quality of patients with diabetes. We aimed to evaluate the efficacy of DSCP in decreasing the hospital mortality of infectious diseases. METHODS: From 1 662 929 patients with type 2 diabetes newly diagnosed between 1999 and 2013, we retrieved a total of 919 patients who participated in the DSCP with the first hospitalisation for an infectious disease as the study cohort and 9190 propensity score-matched patients with type 2 diabetes who did not participate as the comparison.The efficacy of DSCP was evaluated via the following comparisons between the DSCP and non-DSCP cohorts: hospital mortality, 1-year medical cost prior to and during the hospitalisation, and complications, such as receiving mechanical ventilation and intensive care unit admission. The ratio (OR) for hospital mortality of the DSCP participants was calculated by logistical regression. Further stratification analyses were conducted to examine which group of patients with type 2 diabetes benefited the most from the DSCP during hospitalisation for infectious diseases. RESULTS: The DSCP cohort had a lower hospital mortality rate than the non-DSCP participants (2.18% vs 4.82%, p<0.001). The total medical cost during the hospitalisation was lower in the DSCP cohort than in the non-DSCP cohort (NT$72 454±30 429 vs NT$86 385±29 350) (p=0.006). In the logistical regression model, the DSCP participants exhibited a significantly decreased adjusted OR for hospital mortality (adjusted OR=0.42, 95% CI 0.26 to 0.66, p=0.0002). The efficacy of the DSCP was much more prominent in male patients with type 2 diabetes and in patients with lower incomes. CONCLUSION: Participation in the DSCP was associated with a lower risk of hospital mortality for infectious diseases.

An optical system via liquid crystal photonic devices for photobiomodulation.

Photobiomodulation or low-level light therapy (LLLT) has extensive applications based on light-induced effects in biological systems. Photobiomodulation remains controversial because of a poorly understood biochemical mechanism limited by the well-known biphasic dose response or Arndt-Schulz curve. The Arndt-Schulz curve states that an optimal dose of light is a key factor for realizing a therapeutic effect. In this report, we demonstrate a tunable optical system for photobiomodulation to aid physicians in overcoming the constraints of light due to biphasic dose response. The tunable optical system is based on a white light-emitting diode and four liquid crystal (LC) photonic devices: three LC phase retarders, and one LC lens. The output light of the tunable optical system exhibits electrical tunability for the wavelength, energy density and beam size. The operating principle is introduced, and the experimental results are presented. The proposed concept can be further extended to other electrically tunable photonic devices for different clinical purposes for photobiomodulation.

Associations Between Geriatric Syndromes and Mortality in Community-Dwelling Elderly: Results of a National Longitudinal Study in Taiwan.

OBJECTIVE: Although geriatric syndromes have been studied extensively, their interactions with one another and their accumulated effects on life expectancy are less frequently discussed. This study examined whether geriatric syndromes and their cumulative effects are associated with risks of mortality in community-dwelling older adults. METHODS: Data were collected from the Taiwan Longitudinal Study in Aging in 2003, and the participant survival status was followed until December 31, 2007. A total of 2744 participants aged ≥65 years were included in this retrospective cohort study; 634 died during follow-up. Demographic factors, comorbidities, health behaviors, and geriatric syndromes, including underweight, falls, functional impairment, depressive condition, and cognitive impairment, were assessed. Cox proportional hazard regression analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the probability of survival according to the cumulative number of geriatric syndromes. RESULTS: The prevalence of geriatric syndromes increased with age. Mortality was significantly associated with age ≥75 years; male sex; ≤6 years of education; history of stroke, malignancy; smoking; not drinking alcohol; and not exercising regularly. Geriatric syndromes, such as underweight, functional disability, and depressive condition, contributed to the risk of mortality. The accumulative model of geriatric syndromes also predicted higher risks of mortality (N = 1, HR 1.50, 95% CI 1.19-1.89; N = 2, HR 1.69, 95% CI 1.25-2.29; N ≥ 3, HR 2.43, 95% CI 1.62-3.66). CONCLUSIONS: Community-dwelling older adults who were male, illiterate, receiving institutional care, underweight, experiencing a depressive condition, functionally impaired, and engaging in poor health behavior were more likely to have a higher risk of mortality. The identification of geriatric syndromes might help to improve comprehensive care for community-dwelling older adults.

Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates.

A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 µg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.

Optical separation of heterogeneous size distributions of microparticles on silicon nitride strip waveguides.

We demonstrate two complementary optical separation techniques of dielectric particles on the surface of silicon nitride waveguides. Glass particles ranging from 2 µm to 10 µm in diameter are separated at guided powers below 40 mW. The effects of optical, viscous, and frictional forces on the particles are modeled and experimentally shown to enable separation. Particle interactions are investigated and shown to decrease measured particle velocity without interfering with the overall particle separation distribution. The demonstrated separation techniques have the potential to be integrated with microfluidic structures for cell sorting.

Increased risk of developing dementia in patients with bipolar disorder: a nested matched case-control study.

OBJECTIVE: The association between bipolar disorder and subsequent dementia risk is not well established. The objective of this study was to investigate whether patients with bipolar disorder were at an increased risk for developing dementia. METHODS: A conditional logistic regression model was performed using data from the National Health Insurance Research Database, a nationwide dataset in Taiwan. The study sample included 9,304 patients with incident dementia first diagnosed between 2000 and 2009, and 55,500 gender-, age-, and index date-matched subjects without dementia. Cerebrovascular disease, diabetes, hypertension, head injury, chronic pulmonary disease, alcohol-related disorders, substance use disorders, and health system utilization were treated as covariates in the analyses. RESULTS: After controlling for the covariates, bipolar disorder was significantly associated with an increased risk of subsequent dementia [adjusted odds ratio (aOR) = 4.32, 95% confidence interval (CI): 3.21-5.82]. An increased risk of developing dementia was observed in males and females alike (aOR = 4.01, 95% CI: 2.53-6.35 in males; aOR = 4.55, 95% CI: 3.07-6.73 in females). Moreover, a significantly increased risk was observed in subjects diagnosed with dementia before the age of 65 years (aOR = 3.77, 95% CI: 1.78-8.01). CONCLUSIONS: Findings from this study suggest a positive association between the presence of a lifetime history of bipolar disorder and an increased risk of developing dementia. Furthermore, our results also suggest that subjects with bipolar disorder tend to develop dementia in middle age. Going forward, it will be of importance to confirm our findings in different populations.

Factors associated with newly diagnosed tic disorders among children in Taiwan: a 10-year nationwide longitudinal study.

Increased attention has been paid to tic disorders clinically, yet relatively few studies have probed potential factors that account for the occurrence of tic disorders in the general population. In this study, we used data derived from the Taiwan's National Health Insurance Research Database to examine an array of factors related to the diagnosis of tic disorders and to further probe gender heterogeneity in clinical manifestation. Poisson regression analyses were applied to model the effects of birth cohort, period, and age, separately, on tic disorders. A total of 880 newly diagnosed tic disorders were identified from 2002 to 2009 among 100,516 youngsters in the study dataset who were born between 1997 and 2005. The results showed that a significant increase in the adjusted incidence rate ratio (IRR) was observed when age increased, with the highest adjusted IRR found at age 8-9 years. Compared to the time period from 2002 to 2005, an elevated IRR was found in the time period from 2006 to 2009 (adjusted IRR: 1.37; 95% CI: 1.05-1.80). Boys tended to be more likely to receive their initial diagnosis from psychiatrists and have higher comorbid attention-deficit/hyperactivity disorder (ADHD), as compared with their girl counterparts. In conclusion, the findings indicate that the effects of age and period, respectively, influence the occurrence of newly diagnosed tic disorders. Gender difference and higher frequent comorbid ADHD in boys than in girls were observed in this study.

Different impact of the appropriateness of empirical antibiotics for bacteremia among younger adults and the elderly in the ED.

OBJECTIVES: To investigate the clinical impact of age on bacteremia among adults visiting the emergency department (ED). METHODS: Bacteremic adults visiting the ED from January 2008 to December 2008 were identified retrospectively. Demographic characteristics, severity, bacteremic pathogens with in vitro susceptibility, antimicrobial agents, and outcomes determined from chart records were analyzed as a case-control study. RESULTS: Of 518 eligible bacteremic adults, 288 (55.6%) elderly patients (≥65 years old) were case patients and 230 younger patients (<65 years) were regarded as control patients. The 28-day mortality rate was higher in the case patients than that in the control patients (11.8% vs 6.1%, P = .02). The proportion of inappropriate empirical antibiotic therapy between the survivors and nonsurvivors was similar in control patients (69.4% vs 64.3%, P = .77); but for the case patients, the proportion of inappropriate empirical antibiotic therapy in the survivors was lower than that in the non-survivors (27.6% vs 44.1%, P = .04). Of note, inappropriate empirical antibiotic therapy was also one of independent risk factors of 28-day mortality by the multivariate analyses in the case patients (odds ratio [OR] 3.65; P = .049). Other independent predictors of 28-day mortality in case patients included a high Pittsburgh bacteremia score (≥4 points; OR 22.16; P < .001), bacteremia due to foci other than urinary tract infection (OR 9.07; P = .002), malignancy (OR 10.87; P < .001), coronary artery disease (OR 5.68; P = .01), and high serum creatinine (>1.5 mg/dL; OR 3.44; P = .04). CONCLUSIONS: For bacteremic adults, this study demonstrated the impact of inappropriate empirical antibiotic therapy on patients' outcome in the elderly was greater than that in the younger adults.

Efficacy and safety of tigecycline monotherapy compared with vancomycin-aztreonam in the treatment of complicated skin and skin structure infections in patients from India and Taiwan.

BACKGROUND: To compare the monotherapy of tigecycline with vancomycin-aztreonam in hospitalized patients from India and Taiwan with complicated skin and skin structure infections (cSSSIs). METHODS: Safety and efficacy data were analyzed for Indian (n = 86) and Taiwanese (n = 41) patients hospitalized with cSSSIs who participated in two international Phase 3, randomized, double-blind studies. RESULTS: Patients were treated for 5-14 days. Cure rates at the test-of-cure assessment (12-92 days post-therapy) were generally similar between tigecycline and vancomycin-aztreonam in the clinically evaluable populations (India, 83.3% vs. 75.8%; Taiwan, 78.6% vs. 90%) and in the clinical modified intent-to-treat populations (India, 78.6% vs. 66.7%; Taiwan, 73.3% vs. 75.0%). Nausea and vomiting occurred more frequently with tigecycline, but overall safety and tolerability were comparable between the two treatments. CONCLUSIONS: Tigecycline monotherapy is a safe and effective therapy for cSSSIs in geographically distinct populations in Asia.

Trends of HIV and sexually transmitted infections, estimated HIV incidence, and risky sexual behaviors among gay bathhouse attendees in Taiwan: 2004-2008.

Five serial cross-sectional surveys were done at eight gay bathhouses in Taiwan to investigate the trends of HIV and sexually transmitted infections (STIs) and estimated HIV incidence between 2004 and 2008. Bathhouse attendees completed a questionnaire and tests for HIV, syphilis, hepatitis C virus, and amoebiasis. Twenty-nine (38.6%) were identified as having recent HIV-1 infections. There was a significant increase in HIV incidence, from 7.8% in 2004 to 15% in 2007 (χ(2) = 17.59, P-trend <0.001). Recreational drug use is the primary risk behavior. Comprehensive screening programs in gay bathhouses for early detection of HIV and STIs are important.

Suppression of migratory/invasive ability and induction of apoptosis in adenomyosis-derived mesenchymal stem cells by cyclooxygenase-2 inhibitors.

OBJECTIVE: To investigate if stem or progenitor cells are found in adenomyosis and to characterize the role of cyclooxygenase-2 (COX-2) in adenomyosis-derived mesenchymal stem cell (AMSC)-related pathogenesis of adenomyosis. DESIGN: Experimental clinical study. SETTING: University hospital. PATIENT(S): Ten patients with adenomyosis. INTERVENTION(S): Hysterectomy. MAIN OUTCOME MEASURE(S): The gene expression of AMSCs and endometrial mesenchymal stem cells (EMSCs) were analyzed by microarray, quantitative polymerase chain reaction and Western blot. Methylthiazol tetrazolium, proliferation, apoptosis, and migration/invasion assays of AMSCs and EMSCs were evaluated after COX-2 inhibitor treatment. RESULT(S): We isolated nine EMSCs from normal endometrium (n=10) and six AMSCs (n=10) from adenomyosis. The morphology, phenotype, and potential of multilineage differentiation between EMSCs and AMSCs were not significantly different. Using complementary DNA microarrays, the expression profiles of EMSCs are related to those of bone marrow-derived mesenchymal stem cells (BMSCs), but AMSCs are different from EMSCs and BMSCs in the gene profiles. We validated the microarray results and showed that there is increased COX-2 expression in AMSCs compared with EMSCs. Treatment with a COX-2 inhibitor suppressed migration and invasion and induced apoptotic capabilities of AMSCs, but not of EMSCs. CONCLUSION(S): Overexpression of COX-2 in AMSCs may play an important role in the pathogenesis of adenomyosis. COX-2 could be a possible target for treatment and prevention of adenomyosis.

Condom availability inTaiwanese gay bathhouses: the right things in the wrong places.

Gay bathhouses were identified as public venues where men having sex with men are more likely to engage in risky sexual behaviors. This study applied Binson and Woods's (Journal of Homosexuality, 44, 2003) theoretical framework of risk environment/bathhouse setting to (a) describe four domains of bathhouse environments, (b) investigate condom availability in bathhouses, and (c) identify barriers of condom distribution. An ethnographic study was conducted at eight gay bathhouses in Taiwan, including environmental observations, interviews of 16 staff members, and self-administered questionnaires of 409 bathhouse patrons. Condoms were provided upon request in eight bathhouses. Environmental observations showed a poor match between the places where condoms were distributed and where men had sex. Cost and police harassment were two barriers of condom distribution in bathhouses. Our findings highlight the importance of the extension of condom distribution at places where men have sex in gay bathhouses.

Combination carbapenem-sulbactam therapy for critically ill patients with multidrug-resistant Acinetobacter baumannii bacteremia: four case reports and an in vitro combination synergy study.

Infections caused by multidrug-resistant Acinetobacter baumannii have become a therapeutic challenge for clinicians worldwide. Although colistin and tigecycline have been successful in treating patients with these infections, these agents are not available on a worldwide basis. We describe four critically ill patients in Taiwan who were diagnosed with multidrug-resistant Acinetobacter baumannii bacteremia. All bacterial isolates from these patients were resistant to commonly available antibiotics, including carbapenems and sulbactam; however, combination therapy with a carbapenem and sulbactam led to favorable clinical outcomes in all four patients. We also conducted an in vitro study using isolates from these patients that showed that this drug combination had a synergistic effect with enhanced antibacterial activity against the isolates. Thus, a carbapenem-sulbactam combination may be a therapeutic alternative for multidrug-resistant Acinetobacter baumannii bacteremia in countries where colistin and tigecycline are not available for clinical use.

Cefotaxime-ciprofloxacin combination therapy for nontyphoid Salmonella bacteremia and paravertebral abscess after failure of monotherapy.

Therapeutic failure of monotherapy with either a third-generation cephalosporin or a fluoroquinolone against nontyphoid salmonellae has been observed in clinical practice. Combination therapy with both agents is recommended in the literature for treating life-threatening infections. However, we know of no published case reports that indicate a therapeutic advantage of this combination therapy for nontyphoid salmonellae infections. We describe a 60-year-old man who had breakthrough bacteremia with vertebral osteomyelitis and paravertebral abscess caused by Salmonella enterica serotype Choleraesuis. This was not controlled with sequential monotherapy but was eventually cured with cefotaxime-ciprofloxacin combination therapy. The Etest showed that the strain was susceptible to cefotaxime and ciprofloxacin, but resistant to nalidixic acid. Cefotaxime and ciprofloxacin in combination may be considered as an option for difficult-to-treat salmonellosis.