Background:There have been few real-life dose-comparing studies on the efficacy and safety of secukinumab in Chinese patients with plaque psoriasis.We conducted a real-life cohort study to investigate the efficacy and...Background:There have been few real-life dose-comparing studies on the efficacy and safety of secukinumab in Chinese patients with plaque psoriasis.We conducted a real-life cohort study to investigate the efficacy and safety of secukinumab 150 and 300 mg in Chinese patients with moderate-to-severe plaque psoriasis.Methods:A total of 106 patients with moderate-to-severe plaque psoriasis were included in this study.Patients received either secukinumab 150 mg or secukinumab 300 mg according to patients’weights and severity of psoriasis.The treatment continued for at least 24 weeks.The efficacy was evaluated by improvement in the psoriasis area and severity index(PASI)scores.The safety was also analyzed.Results:Fifty-nine patients(55.7%)were treated with secukinumab 300 mg and 47 patients(44.3%)were treated with secukinumab 150 mg.After 12-week treatment,PASI75/90/100 responses were achieved in 100%,97.8%,and 95.7%of patients,respectively,in secukinumab 150 mg group,and the efficacy was maintained to week 24.In secukinumab 300 mg group,PASI75/90/100 responses were achieved in 93.2%,81.4%,and 76.3%of patients,respectively,at week 12.In this group,PASI75/90/100 responses reached 91.5%,86.4%,and 79.9%,respectively,at week 24.Biologic-experienced patients had lower responses than biologic-naïve patients.Secukinumab 150 and 300 mg were well tolerated.Five patients discontinued treatment due to poor response,adverse event,or economic reasons.Conclusions:This real-life study demonstrated that high PASI 90 and PASI 100 responses were achieved in Chinese psoriasis patients receiving secukinumab 150 or 300 mg.Biologic-naïve was associated with better clinical efficacy.展开更多
AIMTo evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. METHODSWe performed a retrospective analysis of treatment outcomes among treatment-na&...AIMTo evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. METHODSWe performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent’s Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA RESULTSNinety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBeAg positive status (OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-naïve and treatment-展开更多
BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase prote...BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the A展开更多
AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis(UC) and to identify predictors of response.METHODS We conducted an observational, prospective and multi-center study in UC patients treat...AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis(UC) and to identify predictors of response.METHODS We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at wk 0 and 14 with the physician's global clinical assessment(PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database.RESULTS Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC(E2) and 70% had extensive UC(E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor(TNF) treatment na?ve, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at wk 14(a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 μg/g, and 170.5 μg/g at wk 14. Being anti-TNF treatment na?ve was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of followup. Only three adverse effects(AEs) were observed during the study; all were mild and golimumab was not interrupted.CONCLUSION This real-life practice study endorses golimumab's promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during the induction phase.展开更多
BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asi...BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asia.AIM To investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODS This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December 2018.They were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more wk.The participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary endpoint.The occurrence of adverse events and drug-drug interactions were recorded.RESULTS In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)patients.Fifty(13.7%)patients were treatment-experienced.Intention-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype 3.Most of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HCV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the adverse events were mild.We found two cases o展开更多
There is a lack of appropriate guidelines for realistic user traces, mobility models, routing protocols, considerations of real-life challenges, etc. for general-purpose mobile ad hoc networks （MANET）. In this paper...There is a lack of appropriate guidelines for realistic user traces, mobility models, routing protocols, considerations of real-life challenges, etc. for general-purpose mobile ad hoc networks （MANET）. In this paper, four laptops are used in an open field environment in four scenarios to evaluate the performances of Internet control message protocol （ICMP） based ping and transmission control protocol （TCP） based streaming video applications using optimised link state routing （OLSR） implementation in an IEEE 802.11g wireless network. Corresponding simulations are developed in Network Simulator ns-2 by setting simulation parameters according to the real experiments. Difficulties faced to regenerate real-life scenarios have been discussed and the gaps between reality and simulation are identified. A setup guideline to produce realistic simulation results has been established.展开更多
BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC...BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.AIM To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic options.METHODS This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death.Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D.Corresponding median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P < 0.0001), respectively. Among BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival (HR = 0.15(CI: 0.04-0.56, P = 0.005))Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71);P= 0.013].CONCLUSION In this real setting, our results were lower than expected. This highlights unmet ne展开更多
We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroen...We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroenterology.Celiac disease is a well-recognized systemic autoimmune disorder.In genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of gluten.For that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to gluten.Research aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small intestine.The study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing conditions.This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.展开更多
Orthostatic hypotension (OH)is a common condition in older persons.According to the 2011criteria,OH is defined by a sustained reduction of systolic blood pressure of 20 mmHg or a 10mmHg-fall of diastolic blood pressur...Orthostatic hypotension (OH)is a common condition in older persons.According to the 2011criteria,OH is defined by a sustained reduction of systolic blood pressure of 20 mmHg or a 10mmHg-fall of diastolic blood pressure,[1] Its prevalence increases with age and according to a recent systematic review the pooled prevalence in community dwelling older people is 22.2%.[2]Although OH is largely explained by concurrent clinical conditions (in particular, hypertension,diabetes,malnutrition,vascular encephalopa- thy,anemia,Parkinson's disease)[3],aging per se determines a series of physiological dysfunctions potentially representing its biological substratum (e.g.,reduction in barore- flex-mediated cardiovascular function,altered salt and water balance at renal level,impaired cardiac diastolic filling).It is also noteworthy that age-related changes in pharmacokinetic and pharmacodynamic mechanisms of drugs (especially in the context of polypharmacy)also increase the risk of OH.展开更多
AIM To detect chronic hepatitis B(CHB),chronic hepatitis C(CHC) and human immunodeficiency virus(HIV) infections in dried blood spot(DBS) and compare these samples to venous blood sampling in real-life.METHODS We incl...AIM To detect chronic hepatitis B(CHB),chronic hepatitis C(CHC) and human immunodeficiency virus(HIV) infections in dried blood spot(DBS) and compare these samples to venous blood sampling in real-life.METHODS We included prospective patients with known viral infections from drug treatment centers,a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper,and a venous blood sample was obtained. The samples were analyzed for HBs Ag,antiHBc,anti-HBs,anti-HCV,and anti-HIV levels as well as subjected to a combined nucleic acid test(NAT) for HBV DNA,HCV RNA and HIV RNA.RESULTS Samples from 404 subjects were screened(85 CHB,116 CHC,114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity,but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS(68% and 42%).CONCLUSION DBS sampling,combined with an automated analysis system,is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system.展开更多
This paper aims at strengthening teachers’understanding as well as optimizing future curriculum design of ESP(Eng⁃lish Specific Purpose).According to the literature ESP is one of the means for language learning and t...This paper aims at strengthening teachers’understanding as well as optimizing future curriculum design of ESP(Eng⁃lish Specific Purpose).According to the literature ESP is one of the means for language learning and teaching,which is based on learners’needs.By adopting needs analysis,teachers are able to deeply and appropriately understand the needs from students and the real-life settings like working places in society.According to the three cases that have been reviewed,there are always discrep⁃ancies between teaching and learning in the classroom,and the real-life needs of job requirements in society.Combining the curric⁃ulum design of ESP and the method of needs analysis is an effective way to close the discrepancy.展开更多
This paper presents a review of the challenges to engineering management in the Big Data Era as well as the Big Data applications. First, it outlines the definitions of big data, data science and intelligent knowledge...This paper presents a review of the challenges to engineering management in the Big Data Era as well as the Big Data applications. First, it outlines the definitions of big data, data science and intelligent knowledge and the history of big data. Second, the paper reviews the academic activities about big data in China. Then, it elaborates a number of challenging big data problems, including transforming semi-structured and non-structured data into"structured format" and explores the relationship of data heterogeneity, knowledge heterogeneity and decision heterogeneity. Furthermore, the paper reports various real-life applications of big data, such as financial and petroleum engineering and internet business.展开更多
AIM To define predictors of functional benefit of direct-acting antivirals(DAAs) in patients with chronic hepatitis C virus(HCV) infection and liver cirrhosis.METHODS We analysed a cohort of 199 patients with chronic ...AIM To define predictors of functional benefit of direct-acting antivirals(DAAs) in patients with chronic hepatitis C virus(HCV) infection and liver cirrhosis.METHODS We analysed a cohort of 199 patients with chronic HCV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated(76%) and decompensated(24%) liver cirrhosis at two tertiary centres in Germany. Patients were included withtreatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression analysis.RESULTS Viral clearance was achieved in 88%(175/199) of patients. Sustained virological response(SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90%(n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57%(n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87%(n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67%(n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37%(65/179) of patients, no change of MELD score in 41%(74/179) of patients, and an aggravation was observed in 22%(40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the Child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional benefit.CONCLUSION Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HCV and with advanced liver disease.展开更多
This study aimed to develop real-life performance-based tasks in Business Mathematics (RLPBTs) following the ADDIE’s model of instructional development. Using the descriptive-developmental research design, the study ...This study aimed to develop real-life performance-based tasks in Business Mathematics (RLPBTs) following the ADDIE’s model of instructional development. Using the descriptive-developmental research design, the study developed RLPBTS with mathematics experts, mathematics department head, bank manager, mathematics teachers, and students as respondents. The RLPBTs consist of instructional plans. Each instructional plan has these components: Introduction, Learning Competency, Learning Outcome, Task Execution, Scoring Guide, and Generalization. The design and content of the instructional plans were assessed as very good. On the other hand, the design and execution of the Tasks were assessed as favorable. Grade 11 students also agreed that real-life performance-based tasks helped them understand better concepts in business mathematics. They claimed that they enjoyed the tasks because of the inclusion of real-life situations that they simulated. The use of the RLPBTs provides another innovation in the teaching and learning concepts in Business Mathematics.展开更多
Sorafenib is a new treatment indicated for patients with advanced renal cell carcinoma who have failed prior cytokine-based therapy or are considered unsuitable for such therapy. Although treatment with sorafenib und...Sorafenib is a new treatment indicated for patients with advanced renal cell carcinoma who have failed prior cytokine-based therapy or are considered unsuitable for such therapy. Although treatment with sorafenib under ‘ideal trial conditions’ has been extensively studied, registration and reimbursement authorities are also interested in the behavior of sorafenib in real-life practice. This study aims to conduct a literature review of the dosage and treatment duration;safety, tolerability and effectiveness;costs and cost-effectiveness of sorafenib in routine clinical care. Studies were identified by searching PubMed, Embase, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, and EconLit up to November 2010. The literature search included articles published in peer-reviewed journals, congress abstracts, and internal studies of Bayer Schering Pharma. Eight studies were included. An open-label study observed stable disease for at least eight weeks in 80% of patients. The most common drug-related adverse events were hand-foot skin reaction, rash, hypertension, and fatigue. Although treatment with sorafenib led to fewer dose reductions, it was also associated with a shorter treatment duration, less time to pro-gression and a shorter survival time as compared to sunitinib. Monthly health care costs were lower with sorafenib as compared to sunitinib. A post-marketing surveillance study showed that patients rated the tolerability and effectiveness of sorafenib as very good, good or sufficient. In conclusion, the current evidence is too limited to derive conclusions and existing studies suffer from methodological shortcomings.展开更多
During the last few years we have witnessed impressive developments in the area of stochastic local search techniques for intelligent optimization and Reactive Search Optimization. In order to handle the complexity, i...During the last few years we have witnessed impressive developments in the area of stochastic local search techniques for intelligent optimization and Reactive Search Optimization. In order to handle the complexity, in the framework of stochastic local search optimization, learning and optimization has been deeply interconnected through interaction with the decision maker via the visualization approach of the online graphs. Consequently a number of complex optimization problems, in particular multiobjective optimization problems, arising in widely different contexts have been effectively treated within the general framework of RSO. In solving real-life multiobjective optimization problems often most emphasis are spent on finding the complete Pareto-optimal set and less on decision-making. However the com-plete task of multiobjective optimization is considered as a combined task of optimization and decision-making. In this paper, we suggest an interactive procedure which will involve the decision-maker in the optimization process helping to choose a single solution at the end. Our proposed method works on the basis of Reactive Search Optimization (RSO) algorithms and available software architecture packages. The procedure is further compared with the excising novel method of Interactive Multiobjective Optimization and Decision-Making, using Evolutionary method (I-MODE). In order to evaluate the effectiveness of both methods the well-known study case of welded beam design problem is reconsidered.展开更多
This paper explores the theoretical foundation o Task-driven Approach in teaching and learning an analyzes an application of this approach in a rea classroom teaching. From the teaching practice an interview the autho...This paper explores the theoretical foundation o Task-driven Approach in teaching and learning an analyzes an application of this approach in a rea classroom teaching. From the teaching practice an interview the author concludes that Task-drive Approach best characterizes the teaching principle o learner-centered, interest-focused, task-based an real-life-related.展开更多
文摘Background:There have been few real-life dose-comparing studies on the efficacy and safety of secukinumab in Chinese patients with plaque psoriasis.We conducted a real-life cohort study to investigate the efficacy and safety of secukinumab 150 and 300 mg in Chinese patients with moderate-to-severe plaque psoriasis.Methods:A total of 106 patients with moderate-to-severe plaque psoriasis were included in this study.Patients received either secukinumab 150 mg or secukinumab 300 mg according to patients’weights and severity of psoriasis.The treatment continued for at least 24 weeks.The efficacy was evaluated by improvement in the psoriasis area and severity index(PASI)scores.The safety was also analyzed.Results:Fifty-nine patients(55.7%)were treated with secukinumab 300 mg and 47 patients(44.3%)were treated with secukinumab 150 mg.After 12-week treatment,PASI75/90/100 responses were achieved in 100%,97.8%,and 95.7%of patients,respectively,in secukinumab 150 mg group,and the efficacy was maintained to week 24.In secukinumab 300 mg group,PASI75/90/100 responses were achieved in 93.2%,81.4%,and 76.3%of patients,respectively,at week 12.In this group,PASI75/90/100 responses reached 91.5%,86.4%,and 79.9%,respectively,at week 24.Biologic-experienced patients had lower responses than biologic-naïve patients.Secukinumab 150 and 300 mg were well tolerated.Five patients discontinued treatment due to poor response,adverse event,or economic reasons.Conclusions:This real-life study demonstrated that high PASI 90 and PASI 100 responses were achieved in Chinese psoriasis patients receiving secukinumab 150 or 300 mg.Biologic-naïve was associated with better clinical efficacy.
文摘AIMTo evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. METHODSWe performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent’s Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA RESULTSNinety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBeAg positive status (OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-naïve and treatment-
基金Supported by the Asociación de Celíacos y Sensibles al Gluten de Madrid,No.ACM2020)and Research Committee Argentine Society of Gastroenterology,No.2020.
文摘BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the A
文摘AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis(UC) and to identify predictors of response.METHODS We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at wk 0 and 14 with the physician's global clinical assessment(PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database.RESULTS Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC(E2) and 70% had extensive UC(E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor(TNF) treatment na?ve, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at wk 14(a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 μg/g, and 170.5 μg/g at wk 14. Being anti-TNF treatment na?ve was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of followup. Only three adverse effects(AEs) were observed during the study; all were mild and golimumab was not interrupted.CONCLUSION This real-life practice study endorses golimumab's promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during the induction phase.
文摘BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asia.AIM To investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODS This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December 2018.They were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more wk.The participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary endpoint.The occurrence of adverse events and drug-drug interactions were recorded.RESULTS In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)patients.Fifty(13.7%)patients were treatment-experienced.Intention-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype 3.Most of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HCV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the adverse events were mild.We found two cases o
文摘There is a lack of appropriate guidelines for realistic user traces, mobility models, routing protocols, considerations of real-life challenges, etc. for general-purpose mobile ad hoc networks （MANET）. In this paper, four laptops are used in an open field environment in four scenarios to evaluate the performances of Internet control message protocol （ICMP） based ping and transmission control protocol （TCP） based streaming video applications using optimised link state routing （OLSR） implementation in an IEEE 802.11g wireless network. Corresponding simulations are developed in Network Simulator ns-2 by setting simulation parameters according to the real experiments. Difficulties faced to regenerate real-life scenarios have been discussed and the gaps between reality and simulation are identified. A setup guideline to produce realistic simulation results has been established.
文摘BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.AIM To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic options.METHODS This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death.Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D.Corresponding median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P < 0.0001), respectively. Among BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival (HR = 0.15(CI: 0.04-0.56, P = 0.005))Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71);P= 0.013].CONCLUSION In this real setting, our results were lower than expected. This highlights unmet ne
文摘We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroenterology.Celiac disease is a well-recognized systemic autoimmune disorder.In genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of gluten.For that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to gluten.Research aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small intestine.The study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing conditions.This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.
文摘Orthostatic hypotension (OH)is a common condition in older persons.According to the 2011criteria,OH is defined by a sustained reduction of systolic blood pressure of 20 mmHg or a 10mmHg-fall of diastolic blood pressure,[1] Its prevalence increases with age and according to a recent systematic review the pooled prevalence in community dwelling older people is 22.2%.[2]Although OH is largely explained by concurrent clinical conditions (in particular, hypertension,diabetes,malnutrition,vascular encephalopa- thy,anemia,Parkinson's disease)[3],aging per se determines a series of physiological dysfunctions potentially representing its biological substratum (e.g.,reduction in barore- flex-mediated cardiovascular function,altered salt and water balance at renal level,impaired cardiac diastolic filling).It is also noteworthy that age-related changes in pharmacokinetic and pharmacodynamic mechanisms of drugs (especially in the context of polypharmacy)also increase the risk of OH.
文摘AIM To detect chronic hepatitis B(CHB),chronic hepatitis C(CHC) and human immunodeficiency virus(HIV) infections in dried blood spot(DBS) and compare these samples to venous blood sampling in real-life.METHODS We included prospective patients with known viral infections from drug treatment centers,a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper,and a venous blood sample was obtained. The samples were analyzed for HBs Ag,antiHBc,anti-HBs,anti-HCV,and anti-HIV levels as well as subjected to a combined nucleic acid test(NAT) for HBV DNA,HCV RNA and HIV RNA.RESULTS Samples from 404 subjects were screened(85 CHB,116 CHC,114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity,but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS(68% and 42%).CONCLUSION DBS sampling,combined with an automated analysis system,is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system.
文摘This paper aims at strengthening teachers’understanding as well as optimizing future curriculum design of ESP(Eng⁃lish Specific Purpose).According to the literature ESP is one of the means for language learning and teaching,which is based on learners’needs.By adopting needs analysis,teachers are able to deeply and appropriately understand the needs from students and the real-life settings like working places in society.According to the three cases that have been reviewed,there are always discrep⁃ancies between teaching and learning in the classroom,and the real-life needs of job requirements in society.Combining the curric⁃ulum design of ESP and the method of needs analysis is an effective way to close the discrepancy.
基金supported by the key research grant"Innovative Research on Management Decision Making under Big Data Environment"(Grant No.71331005)"Non-structured Data Analysis Methods and Key Technologies for Management Decision Making"(Grant No.71501175)the key international collaboration grant"Business Intelligence Methods Based on Optimization Data Mining with Applications of Financial and Banking Management"(Grant No.71110107026)from the National Natural Science Foundation of China
文摘This paper presents a review of the challenges to engineering management in the Big Data Era as well as the Big Data applications. First, it outlines the definitions of big data, data science and intelligent knowledge and the history of big data. Second, the paper reviews the academic activities about big data in China. Then, it elaborates a number of challenging big data problems, including transforming semi-structured and non-structured data into"structured format" and explores the relationship of data heterogeneity, knowledge heterogeneity and decision heterogeneity. Furthermore, the paper reports various real-life applications of big data, such as financial and petroleum engineering and internet business.
文摘AIM To define predictors of functional benefit of direct-acting antivirals(DAAs) in patients with chronic hepatitis C virus(HCV) infection and liver cirrhosis.METHODS We analysed a cohort of 199 patients with chronic HCV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated(76%) and decompensated(24%) liver cirrhosis at two tertiary centres in Germany. Patients were included withtreatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression analysis.RESULTS Viral clearance was achieved in 88%(175/199) of patients. Sustained virological response(SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90%(n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57%(n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87%(n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67%(n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37%(65/179) of patients, no change of MELD score in 41%(74/179) of patients, and an aggravation was observed in 22%(40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the Child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional benefit.CONCLUSION Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HCV and with advanced liver disease.
文摘This study aimed to develop real-life performance-based tasks in Business Mathematics (RLPBTs) following the ADDIE’s model of instructional development. Using the descriptive-developmental research design, the study developed RLPBTS with mathematics experts, mathematics department head, bank manager, mathematics teachers, and students as respondents. The RLPBTs consist of instructional plans. Each instructional plan has these components: Introduction, Learning Competency, Learning Outcome, Task Execution, Scoring Guide, and Generalization. The design and content of the instructional plans were assessed as very good. On the other hand, the design and execution of the Tasks were assessed as favorable. Grade 11 students also agreed that real-life performance-based tasks helped them understand better concepts in business mathematics. They claimed that they enjoyed the tasks because of the inclusion of real-life situations that they simulated. The use of the RLPBTs provides another innovation in the teaching and learning concepts in Business Mathematics.
文摘Sorafenib is a new treatment indicated for patients with advanced renal cell carcinoma who have failed prior cytokine-based therapy or are considered unsuitable for such therapy. Although treatment with sorafenib under ‘ideal trial conditions’ has been extensively studied, registration and reimbursement authorities are also interested in the behavior of sorafenib in real-life practice. This study aims to conduct a literature review of the dosage and treatment duration;safety, tolerability and effectiveness;costs and cost-effectiveness of sorafenib in routine clinical care. Studies were identified by searching PubMed, Embase, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, and EconLit up to November 2010. The literature search included articles published in peer-reviewed journals, congress abstracts, and internal studies of Bayer Schering Pharma. Eight studies were included. An open-label study observed stable disease for at least eight weeks in 80% of patients. The most common drug-related adverse events were hand-foot skin reaction, rash, hypertension, and fatigue. Although treatment with sorafenib led to fewer dose reductions, it was also associated with a shorter treatment duration, less time to pro-gression and a shorter survival time as compared to sunitinib. Monthly health care costs were lower with sorafenib as compared to sunitinib. A post-marketing surveillance study showed that patients rated the tolerability and effectiveness of sorafenib as very good, good or sufficient. In conclusion, the current evidence is too limited to derive conclusions and existing studies suffer from methodological shortcomings.
文摘During the last few years we have witnessed impressive developments in the area of stochastic local search techniques for intelligent optimization and Reactive Search Optimization. In order to handle the complexity, in the framework of stochastic local search optimization, learning and optimization has been deeply interconnected through interaction with the decision maker via the visualization approach of the online graphs. Consequently a number of complex optimization problems, in particular multiobjective optimization problems, arising in widely different contexts have been effectively treated within the general framework of RSO. In solving real-life multiobjective optimization problems often most emphasis are spent on finding the complete Pareto-optimal set and less on decision-making. However the com-plete task of multiobjective optimization is considered as a combined task of optimization and decision-making. In this paper, we suggest an interactive procedure which will involve the decision-maker in the optimization process helping to choose a single solution at the end. Our proposed method works on the basis of Reactive Search Optimization (RSO) algorithms and available software architecture packages. The procedure is further compared with the excising novel method of Interactive Multiobjective Optimization and Decision-Making, using Evolutionary method (I-MODE). In order to evaluate the effectiveness of both methods the well-known study case of welded beam design problem is reconsidered.
文摘This paper explores the theoretical foundation o Task-driven Approach in teaching and learning an analyzes an application of this approach in a rea classroom teaching. From the teaching practice an interview the author concludes that Task-drive Approach best characterizes the teaching principle o learner-centered, interest-focused, task-based an real-life-related.
