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Shao-Huan Lan,1 Chih-Cheng Lai,2 Li-Chin Lu,3 Shen-Peng Chang,4 Hui-Ting Huang41School of Pharmaceutical Sciences and Medical Technology, Putian University, Putian, People’s Republic of China; 2Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan; 3School of Management, Putian University, Putian, People’s Republic of China; 4Department of Pharmacy, Chi Mei Medical Center, Liouying, TaiwanPurpose: To assess the clinical efficacy and safety of delafloxacin for treating acute bacterial skin and skin structure infections (ABSSSIs) in adult patients.Patients and methods: The Cochrane Library, EBSCO, EMBASE, Ovid Medline, PubMed, and Web of Science databases were searched up to November 2018. Only randomized controlled trials (RCTs) that evaluated delafloxacin and other comparators for the treatment of ABSSSIs were included. The primary outcome was the clinical cure rate and the secondary outcomes were microbiological response and the risk of adverse events.Results: Four RCTs were included. Overall, delafloxacin exhibited a clinical cure rate similar to the rates of the comparator drugs in the treatment of ABSSSI (OR, 1.05; 95% CI, 0.87–1.27, I2,=16%) and methicillin-resistant Staphylococcus aureus (MRSA)-associated ABSSSI (OR, 1.12; 95% CI, 0.71–1.77, I2,=0%). Delafloxacin had a microbiological eradication (documented and presumed) rate similar to the rates of the comparators in the treatment of ABSSSI (OR, 1.21; 95% CI, 0.58–2.50, I2,=0%) and MRSA-associated ABSSSIs (OR, 1.16; 95% CI, 0.37–3.60, I2,=0%). Delafloxacin and the comparators did not differ significantly in the risk of serious adverse events (AEs), treatment-emergent adverse events (TEAEs), and TEAEs related to the study drug. However, the risk of discontinuation of the study drug due to an AE was lower for delafloxacin than for the comparators (OR, 0.33; 95% CI, 0.15–0.74, I2,=0%).Conclusion: The clinical efficacy of delafloxacin is as high as that of the comparator drugs in the treatment of ABSSSI, including MRSA-associated infections; furthermore, this antibiotic is as well-tolerated as the comparators.Keywords: delafloxacin, acute bacterial skin and skin structure infections, MRSA, efficacy, safety

Chih-Wei Chen,1,2 Shen-Peng Chang,3 Hui-Ting Huang,4 Hung-Jen Tang,5 Chih-Cheng Lai61Division of Neurosurgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Occupational Safety and Health/Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 3Department of Pharmacy, Chi Mei Medical Center, Liouying, Taiwan; 4School of Pharmacy, China Medical University, Taichung, Taiwan; 5Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; 6Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, TaiwanObjectives: This meta-analysis aims to assess the clinical efficacy and safety of ceftaroline in treating acute bacterial infections – community-acquired pneumonia (CAP) and skin and skin structure infection (SSSI) in pediatric patients.Methods: The Pubmed, Embase, ClinicalTrials.gov. and the Cochrane databases were searched up to December 31, 2018. Only randomized controlled trials (RCTs) evaluating ceftaroline and other comparators in the treatment of acute bacterial infection in pediatric patients were included. The primary outcome was the clinical cure rate and the secondary outcome was the risk of adverse event.Results: Three RCTs were included. Overall, ceftaroline had a clinical cure rate at end of therapy (EOT) and test of cure (TOC) similar to comparators in the treatment of acute bacterial infection (at EOT, OR, 1.93; 95% CI, 0.88–4.25, I2=0%, and at TOC, OR, 1.36; 95% CI, 0.64–2.91, I2=14%). In addition, ceftaroline had a clinical failure rate at EOT and TOC similar to comparators in the treatment of acute bacterial infection (at EOT, OR, 0.62; 95% CI, 0.22–1.76, I2=0%, and at TOC, OR, 0.68; 95% CI, 0.24–1.91, I2=0%). No significant differences were found for the risk of treatment-emergent adverse events (TEAE) in all and different degrees between ceftaroline and comparators (OR, 0.81; 95% CI, 0.37–1.78, I2=56%). The risks of TEAE and severe adverse events related to study drug were similar between ceftaroline and comparators (TEAE related to study drug, OR, 0.98; 95% CI, 0.52–1.82, I2=0%, severe adverse event related to study drug, OR, 1.09; 95% CI, 0.22–5.44, I2=22%).Conclusions: The clinical efficacy of ceftaroline is as good as comparator therapy in the treatment of acute bacterial infections – CAP and SSSI, and this antibiotic is well tolerated as the comparators.Keywords: ceftaroline, acute bacterial infection, pediatric, community-acquired pneumonia, skin and skin structure infection

Hsiang Tso Huang,1 Hsin-Ming Wang,1 Shih-Cheng Yang,1 Wei-Chen Tai,1 Chih-Ming Liang,1 Keng-Liang Wu,1 Chen-Hsiang Lee,2 Seng-Kee Chuah1 1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan; 2Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan Purpose: To assess the efficacy of amoxicillin, tetracycline, high-dose metronidazole, and a proton-pump inhibitor for third-line Helicobacter pylori eradication. Methods: We enrolled 70 consecutive patients who had registered, failed to respond to two rounds of H. pylori eradication, and undergone endoscopy for H. pylori culture. Seven patients were lost to follow-up. Patients were treated according to the results of antibiotic-susceptibility testing reports (cultured group, n=39). Those who failed the H. pylori culture were prescribed 14-day quadruple therapy containing esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily, and metronidazole 500 mg three times daily (empirical group, n=24). A follow-up urea breath test was performed 8 weeks later. Results: Antibiotic-resistance rates were 79.5% (clarithromycin), 94.9% (levofloxacin), 66.7% (metronidazole), 2.6% (amoxicillin), and 0 (tetracycline). Eradication rates attained by the cultured and empirical group were 89.7% (95% CI 72.7%–97.1%) and 58.3% (95% CI 36.6%–77.9%) in per-protocol analysis (P=0.004) and 81.4% (95% CI 66.6%–91.6%) and 51.8% (95% CI 31.9%–71.3%) in intention-to-treat analysis (P=0.014), respectively. Culture-guided therapy was the only clinical factor influencing the efficacy of H. pylori eradication (OR 0.16, 95% CI 0.04–0.60; P=0.006). Despite the high metronidazole-resistance rate (66.7%) after two treatment failures, the eradication rate in patients with this condition was 84%. Conclusion: Empirical 14-day modified quadruple therapy is not acceptable as an alternative third-line rescue H. pylori treatment. The success rate of third-line susceptibility-guided treatment was near 90%. This report is valuable as a reminder to medical practitioners that rather than a try-and-see approach, susceptibility-guided therapy should always be considered whenever possible for patients who have undergone several treatment failures.Keywords: amoxicillin-resistance, metronidazole-resistance, empirical quadruple therapy, culture-guided therapy

Khai-Jing Ng,1,2,* Chih-Wei Tseng,1–4,* Ting-Tsung Chang,5,6 Shinn-Jia Tzeng,7 Yu-Hsi Hsieh,1,2 Tsung-Hsing Hung,1,2 Hsiang-Ting Huang,8 Shu-Fen Wu,9 Kuo-Chih Tseng1,2 1Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, 2School of Medicine, Tzu Chi University, Hualien, 3Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, 4School of Medicine, National Yang-Ming University, Taipei, 5Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, 6Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, 7Department of Agronomy, National Chiayi University, Chia-Yi, 8Department of Nursing, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, 9Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan *These authors contributed equally tothis work Background: The aim of this study was to evaluate the clinically significant predictors of hepatocellular carcinoma (HCC) development among hepatitis C virus (HCV) cirrhotic patients receiving combination therapy.Patients and methods: One hundred and five compensated cirrhosis patients who received pegylated interferon plus ribavirin between January 2005 and December 2011 were enrolled. All the patients were examined with abdominal sonography and liver biochemistry at baseline, end of treatment, and every 3–6 months posttreatment. The occurrence of HCC was evaluated every 3–6 months posttreatment.Results: A total of 105 patients were enrolled (mean age 58.3±10.4 years). The average follow-up time for each patient was 4.38 years (standard deviation 1.73 years; range 1.13–9.27years). Fifteen (14.3%) patients developed HCC during follow-up period. Thirteen of them had high baseline aspartate aminotransferase to platelet ratio index (APRI) (ie, an APRI>2.0). Multivariate analysis showed that those without sustained virologic response (SVR) (hazard ratio [HR] 5.795; 95% confidence interval [CI] 1.370–24.5; P=0.017) and high APRI (HR 5.548; 95% CI 1.191–25.86; P=0.029) had a significantly higher risk of HCC occurrence. The cumulative incidence of HCC was significantly higher (P=0.009) in patients without SVR (3-year cumulative incidence 21.4%; 95% CI 7.4%–35.5%; 5-year cumulative incidence 31.1%; 95% CI 11.2%–51.1%) compared to those with SVR (3- and 5-year cumulative incidence 6.2%; 95% CI 0%–1.3%). Further, the cumulative incidence of HCC was significantly higher (P=0.006) in patients with high APRI (3-year cumulative incidence 21.8%; 95% CI 8.2%–35.3%; 5-year cumulative incidence 30.5%, 95% CI 11.8%–49.3%) compared to those with low APRI (3- and 5-year cumulative incidence 4.2%, 95% CI 0%–1.0%).Conclusion: In HCV-infected cirrhotic patients who received combination therapy, APRI and SVR are the two major predictors of HCC development. Keywords: aspartate aminotransferase to platelet ratio index, chronic hepatitis C, hepatitis C virus, hepatocellular carcinoma, liver cirrhosis, sustained virologic response

Shih-Feng Liu,1–3 Ho-Chang Kuo,1,2,4 Guan-Heng Liu,5 Shu-Chen Ho,4 Huang-Chih Chang,1,3 Hung-Tu Huang,6 Yu-Mu Chen,1 Kuo-Tung Huang,1,3 Kuan-Yi Chen,2 Wen-Feng Fang,1–3 Meng-Chih Lin1–3 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, 2Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, 3Chang Gung University College of Medicine, 4Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, 5Li-Chih Valuable School, 6Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China Background: Whether the use of inhaled corticosteroids (ICSs) in patients with COPD can protect from osteoporosis remains undetermined. The aim of this study is to assess the incidence of osteoporosis in patients with COPD with ICS use and without.Patients and methods: This is a retrospective cohort and population-based study in which weextracted newly diagnosed female patients with COPD between 1997 and 2009 from Taiwan’s National Health Insurance (TNHI) database between 1996 and 2011 (International Classification of Diseases, Ninth Revision – Clinical Modification [ICD-9-CM] 491, 492, 496). The patients with COPD were defined by the presence of two or more diagnostic codes for COPD within 12months on either inpatient or outpatient service claims submitted to TNHI. Patients were excluded if they were younger than 40years or if osteoporosis had been diagnosed prior to the diagnosis of COPD and cases of asthma (ICD-9 CM code 493.X) before the index date. These enrolled patients were followed up till 2011, and the incidence of osteoporosis was determined. The Cox proportional hazards regression model was also used to estimate hazard ratios (HRs) for incidences of lung cancer.Results: Totally, 10,723 patients with COPD, including ICS users (n=812) and nonusers (n=9,911), were enrolled. The incidence rate of osteoporosis per 100,000 person years is 4,395 in nonusers and 2,709 in ICS users (HR: 0.73, 95% confidence interval [CI]: 0.63–084). The higher ICS dose is associated with lower risk of osteoporosis (0mg to ≤20mg, HR: 0.84, 95% CI: 0.69–1.04; >20mg to ≤60mg, HR: 0.78, 95% CI: 0.59–1.04; and >60mg, HR: 0.72, 95% CI: 0.55–0.96; P for trend =0.0023) after adjusting for age, income, and medications. The cumulative osteoporosis probability significantly decreased among the ICS users when compared with the nonusers (P

Chih-Wei Tseng,1,2 Ting-Tsung Chang,3,4 Shinn-Jia Tzeng,5 Yu-Hsi Hsieh,1,2 Tsung-Hsing Hung,1,2 Hsiang-Ting Huang,6 Shu-Fen Wu,7 Kuo-Chih Tseng1,2 1Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, 2School of Medicine, Tzuchi University, Hualien, 3Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, 4Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, 5Department of Agronomy, National Chiayi University, 6Department of Nursing, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 7Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan Objective: We studied the effect of sustained virologic response (SVR) after treatment with pegylated-interferon (PEG-IFN) plus ribavirin on the development of liver cirrhosis in elderly patients with chronic hepatitis C (CHC). Patients and methods: This retrospective study enrolled 145 elderly CHC patients (aged≥65years) who were treatment-naïve and were treated with PEG-IFN plus ribavirin for 6months between January 2005 and December 2011. Abdominal sonography was performed and liver biochemistry was studied at baseline, at the end of treatment, and every 3–6 months thereafter. The development of liver cirrhosis and related complications was evaluated at the follow-ups. The aspartate aminotransferase-to-platelet ratio index was used as a noninvasive maker for fibrosis. Results: The mean patient age was 69.1±3.3years, and the average follow-up time was 5.5years (standard deviation: 2.5years, range: 1.1–12.3years). Ninety-five patients (65.5%) achieved SVR, and 26 (17.9%) discontinued treatment. Twenty-seven patients (18.6%) developed liver cirrhosis after treatment. Patients without SVR had significantly greater risk of liver cirrhosis than those with SVR (hazard ratio [HR]: 3.39, 95% confidence interval [CI]: 1.312–8.761, P=0.012). The difference in 3-year cumulative incidence of liver cirrhosis was 24.8% greater for patients without SVR (35.2%, 95% CI: 13.0–57.5, P=0.012) compared with those with SVR (10.4%, 95% CI: 3.1–17.7). There was a trend of a higher baseline aspartate aminotransferase-to-platelet ratio index score in patients who progressed to liver cirrhosis compared with those who did not progress (2.1±1.2 vs 1.6±1.3, P=0.055), but the difference failed to reach significance by Cox regression (adjusted HR: 1.285, 95% CI: 0.921–1.791, P=0.14). Conclusion: An SVR following PEG-IFN combination treatment can reduce the risk of liver cirrhosis in elderly CHC patients. Keywords: hepatitis C, sustained virologic response, pegylated interferon, ribavirin, liver cirrhosis

The antibiotics resistances to amoxicilln, tetracycline was low in Taiwan even after multiple H. pylori treatment failures and high dose metronidazole could overcome antibiotics resistance. In real world practice, susceptibility-guided treatments are not widely available. Therefore, we assessed the efficacy of 14-day modified quadruple therapy containing amoxicillin, tetracycline and high dose metronidazole and PPI as an empirical third-line rescue H. pylori treatment. This study was conducted by analyzing 70 consecutive prospectively registered patients who failed two times H. pylori eradication. All of them received endoscopy for H. pylori culture. Seven patients were lost to follow up. They were then treated according to the antibiotic susceptibility testing reports (Cultured group, n=39). Those who failed H. pylori culture were prescribed with a modified 14-day quadruple therapy containing esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily and metronidazole 500 mg three times daily (empirical group, n=24). Follow-up urea breath test was performed 8 weeks later. The eradication rates attained by Cultured group and empirical group were 89.7% (95% confidence interval [CI] = 72.72%-97.11%) and 58.3% (95% CI=36.61%-77.86%), in the per protocol analysis (p=0.004); 81.4%(95% CI=66.60%-91.61%) and 51.8% (95% CI=31.9%-71.29%), in the intention-to-treat analysis (p=0.014). Culture-guided therapy was the clinical factors influencing the efficacy of H. pylori eradication (OR: 0.16; 95% CI: 0.04-0.60, p=0.006). In conclusion, empirical 14-day modified 3 quadruple therapy is not acceptable as an alternative third-line rescue H. pylori treatment arobably but the success rate of the third-line susceptibility-guided treatment was only moderate (

Reorganization of the actin cytoskeleton is essential for cell motility and chemotaxis. Actin-binding proteins (ABPs) and membrane lipids, especially phosphoinositides PI(4,5)P2 and PI(3,4,5)P3 are involved in the regulation of this reorganization. At least 15 ABPs have been reported to interact with, or regulated by phosphoinositides (PIPs) whose synthesis is regulated by extracellular signals. Recent studies have uncovered several parallel intracellular signalling pathways that crosstalk in chemotaxing cells. Here, we review the roles of ABPs and phosphoinositides in chemotaxis and cell migration. Linked Articles This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24

Charged multivesicular body protein 1A (CHMP1A; also known as chromatin-modifying protein 1A) is a member of the ESCRT-III (endosomal sorting complex required for transport-III) complex but is also suggested to localize to the nuclear matrix and regulate c

The relatively low expression levels achieved from transferred genes have limited the application of nonviral vectors for gene transfer into the spinal cord in vivo. Thus, the aim of this study was to evaluate the efficacy of electroporation-mediated pro-opiomelanocortin (POMC) gene therapy for neuropathic pain using an animal model of chronic constrictive injury (CCI). Firstly, the optimal pulse characteristics (voltage, pulse duration, number of shocks) were investigated for in vivo electroporation-mediated gene transfer into the spinal cord. The electroporation process makes use of plasmid DNA, which expresses the POMC gene. Expression levels were evaluated in this study by Western blot. We conclude that the optimal conditions for electroporation are a pulse voltage of 200 V, 75-ms duration, 925-ms interval, for five iterations. Secondly, electroporation treatment for neuropathic pain was attempted on CCI rats using plasmid DNA that expresses the POMC gene. Intrathecal administrations of the POMC vector elevated spinal beta-endorphin levels, as manifested in a significantly elevated pain threshold for the CCI limbs. This result suggests that gene therapy for neuropathic pain using this novel technique is very efficacious, and thus shows promise for further clinical trials.