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1.
Gabriella Par Laszlo Szereday Timea Berki Laszlo Palinkas Melinda Halasz Attila Miseta Geza Hegedus Julia Szekeres-Bartho Aron Vincze Bela Hunyady Alajos Par 《PloS one》2013,8(7)
Background
Chronic hepatitis C (CHC) patients achieving rapid virological response (RVR) on PEG-IFN/ribavirin (P/R) therapy have high chance of sustained virological response (SVR). To analyze host immunological factors associated with RVR, viral kinetics, phenotype distribution and Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) were studied prior to and during P/R therapy.Methods
TNF-α, IFN-γ, IL-2, IL-6, IL-4 and IL-10 production by PBMC were measured after Toll-like receptor 4 (TLR-4) or phorbol myristate acetate/Ionomycin stimulation in 20 healthy controls and in 50 CHC patients before receiving and during P/R therapy. RVR was achieved by 14, complete early virological response (cEVR) by 19 patients and 17 patients were null-responders (NR).Results
Patients with RVR showed an increased baseline TNF-α and IL-6 production by TLR-4 activated monocytes and increased IFN-γ, decreased IL-4 and IL-10 production by lymphocytes compared to non-RVR patients. SVR was also associated with increased baseline TNF-α production and decreased IL-10 levels compared to patients who did not achieve SVR. Baseline IL-2 production was higher in cEVR compared to NR patients. Antiviral treatment increased TNF-α, IL-6 production by monocytes and IFN-γ secretion by lymphocytes and decreased IL-4 and IL-10 production by lymphocytes in cEVR compared to NR patients.Conclusion
RVR was associated with increased baseline proinflammatory cytokine production by TLR-4 stimulated monocytes and by activated lymphocytes. In null-responders and in patients who did not achieve SVR both TLR-4 sensing function and proinflammatory cytokine production were impaired, suggesting that modulation of TLR activity and controlled induction of inflammatory cytokine production may provide further therapeutic strategy for CHC patients non-responding to P/R treatment. 相似文献2.
Ming-Lung Yu Chen-Hua Liu Chung-Feng Huang Tai-Chung Tseng Jee-Fu Huang Chia-Yen Dai Zu-Yau Lin Shinn-Cherng Chen Liang-Yen Wang Suh-Hang Hank Juo Wan-Long Chuang Jia-Horng Kao 《PloS one》2012,7(12)
Background
The current stopping rule for peginterferon/ribavirin therapy in hepatitis C virus genotype-1 (HCV-1) patients is based on an early virological response (EVR, defined as >2 log10 viral reduction at treatment week 12). We aimed to explore rapid stopping rules at week 4.Methods
We randomly allocated 528 HCV-1 patients into training and validation sets (at a 1∶2 ratio). The interleukin-28B rs8099917 genotypes and on-treatment virological responses were evaluated to determine the negative predictive value (NPV) for achieving a sustained virological response (SVR, defined as undetectable HCV RNA 24 weeks after end-of-treatment). The study was approved by the ethics committees of the participating hospitals. All of the patients gave written informed consent before enrollment.Results
A poor week 4 response (W4R), defined as a HCV RNA reduction of <1 log10 IU/mL at week 4 or a week 4 HCV RNA>10,000 IU/mL with interleukin-28B non-TT genotype, had the highest NPV (95%). In the complete sample, poor W4R could identify 43.4% (59/136) of the non-responders, with an NPV of 95% and a false negative rate of only 0.8% (3/396). The multivariate analysis revealed that a poor W4R was the most important negative predictor (odds ratio/95% confidence intervals: 49.01/13.70–175.37), followed by the lack of an EVR. In addition to HCV RNA<1 log10 IU/mL reduction, using the criteria of HCV RNA>10,000 IU/mL/non-TT genotype helped identifying an additional one-third of non-SVR patients at W4.Using the strategy of sequential rapid stopping rule strategy could identify 53.7% (73/136) of the non-responders (43.4% at week 4 and an addition 11.3% at week 12), as compared to 40.4% for the classical week-12 early stopping rule.Conclusions
Sequential rapid stopping rules using on-treatment virological responses and interleukin-28B genotype can rapidly identify additional peginterferon/ribavirin non-responders. 相似文献3.
Chung-Feng Huang Chia-Yen Dai Ming-Lun Yeh Jee-Fu Huang Ching-I Huang Ming-Yen Hsieh Zu-Yau Lin Shinn-Cherng Chen Liang-Yen Wang Suh-Hang Hank Juo Wan-Long Chuang Yi-Ching Lin Ming-Lung Yu 《PloS one》2013,8(3)
Background/Aims
The impact of virological factors and interleukin-28B (IL-28B) genetic variants on retreatment of hepatitis C virus genotype 2 (HCV-2) treatment-experienced patients remains unknown.Methods
On-treatment virological responses and IL-28B rs8099917 genotype were determined in 46 HCV-2 treatment-experienced patients (42 previous relapsers; four previous non-responders) retreated with 24-week peginterferon/ribavirin.Results
Forty (87.0%) patients carried the rs8099917 TT genotype and 6 patients (13.0%) carried the TG/GG genotype. The sustained virological response (SVR; seronegativity of HCV RNA throughout 24 weeks of the post-treatment follow-up period) rate was 71.7%. Compared with previous non-responders, previous relapsers had a significantly higher SVR rate (78.6% vs. 0%, P = 0.004) and a lower relapse rate (17.5% vs. 100%, P = 0.04). All the previous non-responders were with the rs8099917 TT genotype. As for those who relapsed, treatment responses, including the rates of rapid virological response (RVR, 80.6% vs. 66.7%, P = 0.59), early virological response (EVR, 97.2% vs. 83.3%, P = 0.27), end-of-treatment virological response (97.2% vs. 83.3%, P = 0.27) and SVR (80.6% vs. 66.7%, P = 0.59) and relapse rate (17.1% vs. 20.0%, P = 1) did not differ significantly between patients with the rs8099917 TT and those with the non-TT genotype. Multivariate analysis revealed that the most important factor predictive of an SVR in the retreatment of HCV-2 was previous relapse; the only factor predictive of an SVR for previous relapsers was the achievement of an EVR. Compared with the achievement of a RVR, the attainment of an EVR was more accurate in predicting an SVR (88% vs. 74%).Conclusions
Peginterferon/ribavirin is effective in the retreatment of HCV-2 relapsers, especially among those who achieved an EVR. 相似文献4.
Halime Silva Barcaui Gerson Carreiro Tavares Silvia Beatriz May Carlos Eduardo Brand?o-Mello Márcia Maria Amendola Pires Paulo Feijó Barroso 《PloS one》2013,8(7)
Background
The standard treatment for chronic hepatitis C virus (HCV) infection in HIV-infected subjects is the combination of alfapeginterferon (PEG-IFN) plus ribavirin. We designed this study to evaluate the rate of SVR and predictors of SVR in a public health setting in Rio de Janeiro, Brazil.Methods
Retrospective cohort study of HCV/HIV co-infected patients treated with PEG-IFN plus ribavirin from 2004 to 2011 in 3 outpatient units in Rio de Janeiro. Exposure variables included age, sex, CD4+ cell count, HCV genotype, HCV and HIV viral loads, liver histology (METAVIR fibrosis scoring system) and previous treatment. The main outcome measurement was SVR.Results
100 patients were included in this analysis. Median age was 47 years and 68% were male. 80%, 4%, 14% and 2% were infected with HCV genotypes 1, 2, 3 and 4, respectively. At baseline, 77% had HCV viral load greater than 800,000 IU/ml, 99% had CD4+ greater than 200 cells/mm3 and 10% had a diagnosis of cirrhosis. The treatment was withdrawn in 9% of the subjects (5% with adverse effects and 4% dropped out). SVR was observed in 27 (27%) of the 100 patients included. 13 (13%) subjects were classified as null-responders, 33(33%) as non-responders, 9 (9%) as breakthrough and 9(9%) as relapsers. In the multivariate model only being infected with genotype 2 or 3 (p<0.01) and having low levels of gamma glutamyl transferase (GGT) at baseline (p = 0.04), were predictive of SVR.Conclusion
SVR in HCV/HIV co-infected subjects in a public health setting is similar to that observed in clinical trials, albeit very low. A delay in therapy initiation should be considered until new therapies as direct acting antiviral drugs (DAA) become widely available and tested in coinfected subjects. 相似文献5.
Emilie Estrabaud Kevin Appourchaux Ivan Bièche Fabrice Carrat Martine Lapalus Olivier Lada Michelle Martinot-Peignoux Nathalie Boyer Patrick Marcellin Michel Vidaud Tarik Asselah 《PloS one》2015,10(4)
Although, the treatment of chronic hepatitis C (CHC) greatly improved with the use of direct antiviral agents, pegylated-interferon (PEG-IFN) plus ribavirin remains an option for many patients, worldwide. The intra-hepatic level of expression of interferon stimulated genes (ISGs) and the rs12979860 CC genotype located within IFNL3 have been associated with sustained virological response (SVR), in patients with CHC. The aim of the study was to identify micro-RNAs associated with SVR and to build an accurate signature to predict SVR. Pre-treatment liver biopsies from 111 patients, treated with PEG-IFN plus ribavirin, were studied. Fifty-seven patients had SVR, 36 non-response (NR) and 18 relapse (RR). The expression of 851 human miRNAs and 30 selected mRNAs, including ISGs, was assessed by RT-qPCR. In the first group of patients (screen), 20 miRNAs out of the 851 studied were deregulated between NRs and SVRs. From the 4 miRNAs validated (mir-23a, mir-181a*, mir-217 and mir-99a), in the second group of patients (validation), 3 (mir-23a, mir-181a* and mir-99a) were down-regulated in NRs as compared to SVRs. The ISGs, studied, were accumulated in SVRs and IFNL3 rs12979860 CT/TT carriers compared respectively to NRs and CC carriers. Combining, clinical data together with the expression of selected genes and micro-RNAs, we identified a signature (IFI35, mir-99a and HCV genotype) to predict SVR (AUC:0.876) with a positive predictive value of 86.54% with high sensibility (80%) and specificity (80.4%). This signature may help to characterize patients with low chance to respond to PEG-IFN/ribavirin and to elucidate mechanisms of NR. 相似文献
6.
Tarik Asselah Alex J. Thompson Robert Flisiak Manuel Romero-Gomez Diethelm Messinger Georgios Bakalos Mitchell L. Shiffman 《PloS one》2016,11(3)
Background
Access to direct-acting antiviral agents (DAAs) is restricted in some settings; thus, the European Association for the Study of the Liver recommends dual peginterferon/ribavirin (PegIFN/RBV) therapy wherever DAAs are unavailable. HCV genotype (GT) 3 infection is now the most difficult genotype to eradicate and PegIFN/RBV remains an effective option. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV therapy.Methods
Relationships between baseline characteristics and SVR were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies.Results
The score was validated using a database of 473 patients. Scores were assigned for six factors as follows: age (years) (≤40: 2 points; >40 but ≤55: 1); bodyweight (kg) (<70: 2; ≥70 but <90: 1); no cirrhosis/transition to cirrhosis (2); ALT ≤2.5 x ULN (1); platelets (109/L) (>200: 2; ≥100 but <200: 1); HCV RNA (<400,000 IU/mL: 1). The points are summed to arrive at a score ranging from 0‒10 where higher scores indicate higher chances of SVR; 141, 123, 203, 249, 232, and 218 patients had total scores of 0‒4, 5, 6, 7, 8, and 9–10, respectively, among whom SVR rates were 45%, 62%, 72%, 76%, 84%, and 89%. Among 622 patients who had scores of 6‒10 and HCV RNA <50 IU/mL by treatment week 4 the SVR rate was 86% (532/622).Conclusions
A simple baseline scoring system involving age, bodyweight, cirrhosis status, ALT level, platelet count and HCV RNA level can be used to identify treatment-naive Caucasian patients with HCV GT3 infection with a high probability of SVR with PegIFN alfa-2a/RBV therapy. 相似文献7.
Cristina Cheroni Lorena Donnici Alessio Aghemo Francesca Balistreri Annalisa Bianco Valeria Zanoni Massimiliano Pagani Roberta Soffredini Roberta D’Ambrosio Maria Grazia Rumi Massimo Colombo Sergio Abrignani Petra Neddermann Raffaele De Francesco 《PloS one》2015,10(9)
Hepatitis C virus (HCV) variants characterized by genomic deletions in the structural protein region have been sporadically detected in liver and serum of hepatitis C patients. These defective genomes are capable of autonomous RNA replication and are packaged into infectious viral particles in cells co-infected with the wild-type virus. The prevalence of such forms in the chronically HCV-infected population and the impact on the severity of liver disease or treatment outcome are currently unknown. In order to determine the prevalence of HCV defective variants and to study their association with clinical characteristics, a screening campaign was performed on pre-therapy serum samples from a well-characterized cohort of previously untreated genotype 1 HCV-infected patients who received treatment with PEG-IFNα and RBV. 132 subjects were successfully analyzed for the presence of defective species exploiting a long-distance nested PCR assay. HCV forms with deletions predominantly affecting E1, E2 and p7 proteins were found in a surprising high fraction of the subjects (25/132, 19%). Their presence was associated with patient older age, higher viral load and increased necroinflammatory activity in the liver. While the presence of circulating HCV carrying deletions in the E1-p7 region did not appear to significantly influence sustained virological response rates to PEG-IFNα/RBV, our study indicates that the presence of these subgenomic HCV mutants could be associated with virological relapse in patients who did not have detectable viremia at the end of the treatment. 相似文献
8.
Glisic S Veljkovic N Jovanovic Cupic S Vasiljevic N Prljic J Gemovic B Perovic V Veljkovic V 《The protein journal》2012,31(2):129-136
Hepatitis C virus (HCV) infection is a major and rising global health problem, affecting about 170 million people worldwide.
The current standard of care treatment with interferon alpha and ribavirin in patients with the genotype 1 infection, the
most frequent genotype in the USA and Western Europe, leads to a successful outcome in only about 50% of individuals. Accurate
prediction of hepatitis C treatment response is of great benefit to patients and clinicians. The informational spectrum method,
a virtual spectroscopy method for structure/function analysis of nucleotide and protein sequences, is applied here for the
identification of the conserved information of the HCV proteins that correlate with the combination therapy outcome. Among
the HCV proteins that we have analyzed the informational property of the p7 of HCV genotype 1b was best related to the therapy
outcome. On the basis of these results, a simple bioinformatics criterion that could be useful in assessment of the response
of HCV-infected patients to the combination therapy has been proposed. 相似文献
9.
I-Cheng Lee Yi-Hsiang Huang Chien-Wei Su Yuan-Jen Wang Teh-Ia Huo Kuei-Chuan Lee Han-Chieh Lin 《PloS one》2013,8(10)
Background and Aims
There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR.Methods
Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of treatment.Results
Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg, IP-10 and IFN-γ levels at week 12. In multivariate analysis, pre-treatment CXCL9 >80 pg/mL, HBV DNA <2.5 x 107 IU/mL and on-treatment HBV viral load, HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 107 IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%).Conclusions
Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads. 相似文献10.
Chi-Chieh Yang Wei-Lun Tsai Wei-Wen Su Chung-Feng Huang Pin-Nan Cheng Ching-Chu Lo Kuo-Chih Tseng Lein-Ray Mo Chun-Hsiang Wang Shih-Jer Hsu Hsueh-Chou Lai Chien-Wei Su Chun-Jen Liu Cheng-Yuan Peng Ming-Lung Yu 《PloS one》2015,10(9)
The efficacy and safety of the boceprevir (BOC)-containing triple therapy in Taiwanese treatment-experienced patients remains elusive. After 4 weeks of peginterferon/ribavirin lead-in therapy, patients with cirrhosis or previous null-response received triple therapy for 44 weeks; whereas others received 32 weeks of triple therapy followed by 12 weeks of peginterferon/ribavirin therapy. Patients with HCV RNA > 100 IU/mL at week 12 or with detectable HCV RNA at week 24 of treatment were viewed as futile. A total of 123 patients received treatment. The rates of sustained virological response (SVR) and relapse were 66.7% and 8.9%, respectively by using intention-to-treat analysis. Multivariate analysis revealed that factors associated with SVR included HCV-1b (odds ratio [OR]/ 95% confidence intervals [CI]: 19.23/1.76–525.15, P = 0.01), BOC adherence (7.69/1.55–48.78, P = 0.01), serum albumin (OR/CI:6.25/1.14–40.07, P = 0.03) levels and HCV RNA levels (OR/CI:0.34/0.12–0.79, P = 0.01). Twenty-six (21.1%) patients experienced severe adverse events (SAEs). Multivariate analysis revealed that APRI > 1.5 was the single factor associated with occurring SAEs (OR/CI: 3.77/ 0.97–14.98, P = 0.05). Merging the cut-off values of HCV RNA > 7 log IU/mL at baseline and HCV RNA > 6 log IU/mL at week 4 provided the earliest and best combing viral kinetics in predicting week 12/24 futility with the PPV of 100% and accuracy of 93.5%. HCV-1 treatment experienced Taiwanese patients treated with boceprevir-containing triple therapy in real world had comparable efficacy and safety profiles with those reported in clinical trials. Early viral kinetics before week 4 of treatment highly predicted futility at week 12 or 24 of treatment. 相似文献
11.
Benjamin Heidrich Hans-J?rg Cordes Hartwig Klinker Bernd M?ller Uwe Naumann Martin R?ssle Michael R. Kraus Klaus H. B?ker Christoph Roggel Marcus Schuchmann Albrecht Stoehr Andreas Trein Svenja Hardtke Andrea Gonnermann Armin Koch Heiner Wedemeyer Michael P. Manns Markus Cornberg 《PloS one》2015,10(6)
Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group.
Trial Registration
ClinicalTrials.gov NCT00803309 相似文献12.
《PLoS medicine》2012,9(4)
Background
At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term.Methods and Findings
We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34+0 and 37+0 wk of gestation. Participants were randomly allocated in a 1∶1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate.From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported.Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM.Conclusions
In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM.Trial registration
Current Controlled Trials ISRCTN29313500 Please see later in the article for the Editors'' Summary 相似文献13.
Hiroshi Sakugawa Hiroki Nakasone Tomofumi Nakayoshi Yuko Kawakami Fukunori Kinjo Atsushi Saito Tomokuni Nakayoshi Akihiro Yamashiro 《Microbiology and immunology》1998,42(4):299-303
Nearly all patients infected with hepatitis C virus (HCV) genotype 1b have reactivity to the core (c22-3) or non-structural (NS)-3 region (c33c) protein in a second-generation recombinant immunoblot assay (RIBA-2). However, reactivities to the NS-4 region antigens (5-1-1, c100-3) vary among patients. To clarify whether differences in serological reactivities to the NS-4 antigens are associated with the clinical features or response to interferon (IFN) therapy of patients infected with hepatitis C virus (HCV) genotype 1b, we clinically investigated 115 such patients. Positive reactions to 5-1-1 and c100-3 were seen in 75.7 and 79.1%, respectively, of the patients. There were no differences between the patients with and those without antibodies to NS-4 region antigens (5-1-1, c100-3) with regard to age, duration of HCV infection, severity of liver disease and virus load. Fifty-one of the patients were treated with recombinant IFN-α, and 17 of the 51 patients showed sustained response to the therapy. The sustained response was more frequently seen in the patients positive for antibodies to both 5-1-1 and c100-3 as compared with those negative for either or both antibodies (41.0% vs. 8.3%, P < 0.05). 相似文献
14.
Background
The use of chemotherapy has been proposed to increase the effectiveness of best supportive care (BSC) in patients with non-small cell lung cancer (NSCLC). Previous trials reported inconsistent findings regarding the efficacy and safety of chemotherapy on overall survival (OS) and treatment-related mortality. We performed a systematic review and meta-analysis to evaluate the effects of chemotherapy plus BSC versus BSC alone on survival of patients with NSCLC.Methodology and Principal Findings
We systematically searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials for relevant literature. All eligible studies included patients with NSCLC who had received chemotherapy and BSC or BSC alone. All eligible studies measured at least 1 of the following outcomes: OS or treatment-related mortality. Overall, patients that received chemotherapy plus BSC had significant longer OS than those that received BSC alone (HR, 0.76; 95%CI, 0.69–0.84; P<0.001). Additionally, chemotherapy plus BSC as compared to BSC alone resulted in a 28% RR reduction (95%CI: 12–40; P = 0.001) in 6-month mortality, 11% RR reduction (95%CI: 8–15; P<0.001) in 12-month mortality, and 5% RR reduction (95%CI: 1–8; P = 0.02) in 2-year mortality. Toxicity was greater in patients that received chemotherapy plus BSC.Conclusion/Significance
Chemotherapy plus BSC increased the OS and reduced the 6-month, 12-month, and 2-year mortality of NSCLC patients. 相似文献15.
Yun-Sook Lim Men T.N. Nguyen Thuy X. Pham Trang T.X. Huynh Eun-Mee Park Dong Hwa Choi Sang Min Kang Dongseob Tark Soon B. Hwang 《Molecules and cells》2022,45(3):148
Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance. Telomere length decreases in patients with active HCV, chronic liver disease, and hepatocellular carcinoma. However, the molecular mechanism of telomere length shortening in HCV-associated disease is largely unknown. In the present study, protein interactions between NS5A and TEN1 were confirmed by immunoprecipitation assays. Silencing of TEN1 reduced both viral RNA and protein expression levels of HCV, while ectopic expression of the siRNA-resistant TEN1 recovered the viral protein level, suggesting that TEN1 was specifically required for HCV propagation. Importantly, we found that TEN1 is re-localized from the nucleus to the cytoplasm in HCV-infected cells. These data suggest that HCV exploits TEN1 to promote viral propagation and that telomere protection is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the telomere shortening in HCV-infected cells. 相似文献
16.
Maria Rubio-Valera Judith Bosmans Ana Fernández Maite Pe?arrubia-María Marian March Pere Travé Juan A. Bellón Antoni Serrano-Blanco 《PloS one》2013,8(8)
Background
Non-adherence to antidepressants generates higher costs for the treatment of depression. Little is known about the cost-effectiveness of pharmacist''s interventions aimed at improving adherence to antidepressants. The study aimed to evaluate the cost-effectiveness of a community pharmacist intervention in comparison with usual care in depressed patients initiating treatment with antidepressants in primary care.Methods
Patients were recruited by general practitioners and randomized to community pharmacist intervention (87) that received an educational intervention and usual care (92). Adherence to antidepressants, clinical symptoms, Quality-Adjusted Life-Years (QALYs), use of healthcare services and productivity losses were measured at baseline, 3 and 6 months.Results
There were no significant differences between groups in costs or effects. From a societal perspective, the incremental cost-effectiveness ratio (ICER) for the community pharmacist intervention compared with usual care was €1,866 for extra adherent patient and €9,872 per extra QALY. In terms of remission of depressive symptoms, the usual care dominated the community pharmacist intervention. If willingness to pay (WTP) is €30,000 per extra adherent patient, remission of symptoms or QALYs, the probability of the community pharmacist intervention being cost-effective was 0.71, 0.46 and 0.75, respectively (societal perspective). From a healthcare perspective, the probability of the community pharmacist intervention being cost-effective in terms of adherence, QALYs and remission was of 0.71, 0.76 and 0.46, respectively, if WTP is €30,000.Conclusion
A brief community pharmacist intervention addressed to depressed patients initiating antidepressant treatment showed a probability of being cost-effective of 0.71 and 0.75 in terms of improvement of adherence and QALYs, respectively, when compared to usual care. Regular implementation of the community pharmacist intervention is not recommended.Trial Registration
ClinicalTrials.gov NCT00794196相似文献17.
Karl Peter Kapitza Torsten Passie Michael Bernateck Matthias Karst 《Applied psychophysiology and biofeedback》2010,35(3):207-217
Previous studies reported that respiratory feedback (RFB) aids in alleviating chronic pain. However, to date, this adjunct treatment has not been rigorously tested against non-contingent (placebo) feedback. Forty-two patients with chronic low back pain were randomized to either RFB or non-contingent RFB. Both groups performed a daily 30-min home training for 15 consecutive days. A respiratory associated relaxation index (RI) was measured. Pain levels and a somatosensory profile were assessed before and after intervention. Additionally, pain levels were assessed 3 months after the end of intervention. Secondary outcome parameters included daily functioning, psychopathology, and suggestibility. T-tests showed higher and significant pain reductions for RFB, compared to non-contingent RFB. Between-group comparisons reached no significance. However, changes were more pronounced in the RFB condition, which was also true for the course of the RI and the psychopathological scores. This is the first study using a non-contingent respiratory placebo feedback in a randomized, controlled design. Within this design previous positive findings of symptom reductions in patients treated with RFB could partially replicated. Nonetheless, tendencies suggest that contingent feedback patients compared to placebo patients profit more from RFB in the long run regarding reduction of chronic pain and psychological distress. 相似文献
18.
Saba M. Lambert Digafe T. Alembo Shimelis D. Nigusse Lawrence K. Yamuah Stephen L. Walker Diana N. J. Lockwood 《PLoS neglected tropical diseases》2016,10(4)
Background
Leprosy Type 1 (T1R) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands, feet and eyes. Type 1 Reactions are treated with oral corticosteroids. There is little evidence on alternative treatments for patients who do not respond to steroids or experience steroid adverse effects. We report the results of a randomized controlled trial testing the efficacy and adverse effect profile of ciclosporin and prednisolone (CnP) in comparison to prednisolone only (P) in patients with new T1R in Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using a clinical severity score, recurrence rate, adverse events and quality of life.Results
Seventy three patients with new T1R were randomized to receive CnP or P for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs 88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and motor (75% vs 74%) loss were higher (but not significantly so) in the patients on CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were similar in patients in the two treatment arms of the study. Both groups had a significant improvement in their quality of life after the study, measured by the SF-36.Conclusions
This is the first double-blind RCT assessing ciclosporin, in the management of T1R in Africa. Ciclosporin could be a safe alternative second-line drug for patients with T1R who are not improving with prednisolone or are experiencing adverse events related to prednisolone. This study illustrates the difficulty in switching off leprosy inflammation. Better treatment agents for leprosy patients with reactions and nerve damage are needed. 相似文献19.
Anuja P. Shah Jenny I. Shen Ying Wang Lili Tong Youngju Pak Ali Andalibi Janine A. LaPage Sharon G. Adler 《PloS one》2016,11(3)
Background
We tested minocycline as an anti-proteinuric adjunct to renin-angiotensin-aldosterone system inhibitors (RAASi) in diabetic nephropathy (DN) and measured urinary biomarkers to evaluate minocycline’s biological effects.Methods
Design: Prospective, single center, randomized, placebo-controlled, intention-to-treat pilot trial. Inclusion. Type 2 diabetes/DN; Baseline creatinine clearance > 30 mL/min; proteinuria ≥ 1.0 g/day; Age ≥30 years; BP <150/95 mm Hg; intolerant of/at maximum RAASi dose. Protocol. 3-wk screening; Baseline randomization; Urine and blood measures at months 1, 2, 4, and Month 6 study completion. Urine interleukin-6 (IL-6) and osteoprotegerin were measured in a subset. Primary outcome. Natural log of urine protein/creatinine (ln U P:Cr) ratio at Month 6 vs Baseline.Results
30 patients completed the study. The 15% decline in U P: Cr in minocycline patients (6 month P:Cr ÷ Baseline P:Cr, 0.85 vs. 0.92) was not significant (p = 0.27). Creatinine clearance did not differ in the 2 groups. Urine IL-6:Cr (p = 0.03) and osteoprotegerin/Cr (p = 0.046) decrements were significant. Minocycline modified the relationship between urine IL-6 and proteinuria, suggesting a protective biological effect.Conclusions
Although the decline in U P:Cr in minocycline patients was not statistically significant, the significant differences in urine IL-6 and osteoprotegerin suggest that minocycline may confer cytoprotection in patients with DN, providing a rationale for further study.Trial Registration
Clinicaltrials.gov NCT01779089相似文献20.
Severine Margeridon-Thermet Sophie Le Pogam Lewyn Li Tommy F. Liu Nancy Shulman Robert W. Shafer Isabel Najera 《PloS one》2014,9(8)