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Article ; Online: The role of extracellular histone in organ injury.

Silk, Eleanor / Zhao, Hailin / Weng, Hao / Ma, Daqing

2017 Volume 8, Issue 5, Page(s) e2812

Abstract: Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into ... ...

Abstract	Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease. Once in the extracellular space, histones act as damage-associated molecular pattern proteins, activating the immune system and causing further cytotoxicity. They interact with Toll-like receptors (TLRs), complement and the phospholipids of cell membranes inducing endothelial and epithelial cytotoxicity, TLR2/TLR4/TLR9 activation and pro-inflammatory cytokine/chemokine release via MyD88, NFκB and NLRP3 inflammasome-dependent pathways. Drugs that block the release of histone, neutralise circulating histone or block histone signal transduction provide significant protection from mortality in animal models of acute organ injury but warrant further research to inform future clinical applications.
Language	English
Publishing date	2017-05-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/cddis.2017.52
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Article: Genetic evidence further elucidates the history and extent of badger introductions from Great Britain into Ireland.

Allen, Adrian / Guerrero, Jimena / Byrne, Andrew / Lavery, John / Presho, Eleanor / Courcier, Emily / O'Keeffe, James / Fogarty, Ursula / Delahay, Richard / Wilson, Gavin / Newman, Chris / Buesching, Christina / Silk, Matthew / O'Meara, Denise / Skuce, Robin / Biek, Roman / McDonald, Robbie A

Royal Society open science

2020 Volume 7, Issue 4, Page(s) 200288

Abstract: The colonization of Ireland by mammals has been the subject of extensive study using genetic methods and forms a central problem in understanding the phylogeography of European mammals after the Last Glacial Maximum. Ireland exhibits a depauperate mammal ...

Abstract	The colonization of Ireland by mammals has been the subject of extensive study using genetic methods and forms a central problem in understanding the phylogeography of European mammals after the Last Glacial Maximum. Ireland exhibits a depauperate mammal fauna relative to Great Britain and continental Europe, and a range of natural and anthropogenic processes have given rise to its modern fauna. Previous Europe-wide surveys of the European badger (
Language	English
Publishing date	2020-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2787755-3
ISSN	2054-5703
ISSN	2054-5703
DOI	10.1098/rsos.200288
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Article ; Online: Genetic evidence further elucidates the history and extent of badger introductions from Great Britain into Ireland

Adrian Allen / Jimena Guerrero / Andrew Byrne / John Lavery / Eleanor Presho / Emily Courcier / James O'Keeffe / Ursula Fogarty / Richard Delahay / Gavin Wilson / Chris Newman / Christina Buesching / Matthew Silk / Denise O'Meara / Robin Skuce / Roman Biek / Robbie A. McDonald

Royal Society Open Science, Vol 7, Iss

2020 Volume 4

Abstract	The colonization of Ireland by mammals has been the subject of extensive study using genetic methods and forms a central problem in understanding the phylogeography of European mammals after the Last Glacial Maximum. Ireland exhibits a depauperate mammal fauna relative to Great Britain and continental Europe, and a range of natural and anthropogenic processes have given rise to its modern fauna. Previous Europe-wide surveys of the European badger (Meles meles) have found conflicting microsatellite and mitochondrial DNA evidence in Irish populations, suggesting Irish badgers have arisen from admixture between human imported British and Scandinavian animals. The extent and history of contact between British and Irish badger populations remains unclear. We use comprehensive genetic data from Great Britain and Ireland to demonstrate that badgers in Ireland's northeastern and southeastern counties are genetically similar to contemporary British populations. Simulation analyses suggest this admixed population arose in Ireland 600–700 (CI 100–2600) years before present most likely through introduction of British badgers by people. These findings add to our knowledge of the complex colonization history of Ireland by mammals and the central role of humans in facilitating it.
Keywords	badgers ; ireland ; britain ; genetics ; phylogeography ; colonization ; Science ; Q
Subject code	941
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	The Royal Society
Document type	Article ; Online
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Article ; Online: Safety and Immunogenicity of ChAd63/MVA Pfs25-IMX313 in a Phase I First-in-Human Trial.

de Graaf, Hans / Payne, Ruth O / Taylor, Iona / Miura, Kazutoyo / Long, Carol A / Elias, Sean C / Zaric, Marija / Minassian, Angela M / Silk, Sarah E / Li, Lee / Poulton, Ian D / Baker, Megan / Draper, Simon J / Gbesemete, Diane / Brendish, Nathan J / Martins, Filipa / Marini, Arianna / Mekhaiel, David / Edwards, Nick J /

Roberts, Rachel / Vekemans, Johan / Moyle, Sarah / Faust, Saul N / Berrie, Eleanor / Lawrie, Alison M / Hill, Fergal / Hill, Adrian V S / Biswas, Sumi

Frontiers in immunology

2021 Volume 12, Page(s) 694759

Abstract: Background: Transmission blocking vaccines targeting the sexual-stages of the malaria parasite could play a major role to achieve elimination and eradication of malaria. The : Methods: Clinical trial looking at safety and immunogenicity of two ... ...

Abstract	Background: Transmission blocking vaccines targeting the sexual-stages of the malaria parasite could play a major role to achieve elimination and eradication of malaria. The Methods: Clinical trial looking at safety and immunogenicity of two recombinant viral vectored vaccines encoding Pfs25-IMX313 in healthy malaria-naive adults. Replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding Pfs25-IMX313, were delivered by the intramuscular route in a heterologous prime-boost regimen using an 8-week interval. Safety data and samples for immunogenicity assays were taken at various time-points. Results: The reactogenicity of the vaccines was similar to that seen in previous trials using the same viral vectors encoding other antigens. The vaccines were immunogenic and induced both antibody and T cell responses against Pfs25, but significant transmission reducing activity (TRA) was not observed in most volunteers by standard membrane feeding assay. Conclusion: Both vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. However, the transmission reducing activity of the antibodies generated were weak, suggesting the need for an alternative vaccine formulation. Trial registration: Clinicaltrials.gov NCT02532049.
MeSH term(s)	Antibodies, Protozoan/blood ; Cells, Cultured ; England ; Healthy Volunteers ; Humans ; Immunization ; Immunogenicity, Vaccine ; Malaria Vaccines/administration & dosage ; Malaria Vaccines/adverse effects ; Malaria Vaccines/immunology ; Malaria, Falciparum/immunology ; Malaria, Falciparum/parasitology ; Malaria, Falciparum/prevention & control ; Malaria, Falciparum/transmission ; Plasmodium falciparum/immunology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/parasitology ; Time Factors ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/adverse effects ; Vaccines, Synthetic/immunology
Chemical Substances	Antibodies, Protozoan ; Malaria Vaccines ; Vaccines, Synthetic
Language	English
Publishing date	2021-07-14
Publishing country	Switzerland
Document type	Clinical Trial, Phase I ; Comparative Study ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.694759
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Article ; Online: Author Correction: T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial.

Ewer, Katie J / Barrett, Jordan R / Belij-Rammerstorfer, Sandra / Sharpe, Hannah / Makinson, Rebecca / Morter, Richard / Flaxman, Amy / Wright, Daniel / Bellamy, Duncan / Bittaye, Mustapha / Dold, Christina / Provine, Nicholas M / Aboagye, Jeremy / Fowler, Jamie / Silk, Sarah E / Alderson, Jennifer / Aley, Parvinder K / Angus, Brian / Berrie, Eleanor /

Bibi, Sagida / Cicconi, Paola / Clutterbuck, Elizabeth A / Chelysheva, Irina / Folegatti, Pedro M / Fuskova, Michelle / Green, Catherine M / Jenkin, Daniel / Kerridge, Simon / Lawrie, Alison / Minassian, Angela M / Moore, Maria / Mujadidi, Yama / Plested, Emma / Poulton, Ian / Ramasamy, Maheshi N / Robinson, Hannah / Song, Rinn / Snape, Matthew D / Tarrant, Richard / Voysey, Merryn / Watson, Marion E E / Douglas, Alexander D / Hill, Adrian V S / Gilbert, Sarah C / Pollard, Andrew J / Lambe, Teresa

Nature medicine

2021 Volume 27, Issue 6, Page(s) 1116

Language	English
Publishing date	2021-05-19
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-021-01363-0
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Article ; Online: Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination.

Minassian, Angela M / Silk, Sarah E / Barrett, Jordan R / Nielsen, Carolyn M / Miura, Kazutoyo / Diouf, Ababacar / Loos, Carolin / Fallon, Jonathan K / Michell, Ashlin R / White, Michael T / Edwards, Nick J / Poulton, Ian D / Mitton, Celia H / Payne, Ruth O / Marks, Michael / Maxwell-Scott, Hector / Querol-Rubiera, Antonio / Bisnauthsing, Karen / Batra, Rahul /

Ogrina, Tatiana / Brendish, Nathan J / Themistocleous, Yrene / Rawlinson, Thomas A / Ellis, Katherine J / Quinkert, Doris / Baker, Megan / Lopez Ramon, Raquel / Ramos Lopez, Fernando / Barfod, Lea / Folegatti, Pedro M / Silman, Daniel / Datoo, Mehreen / Taylor, Iona J / Jin, Jing / Pulido, David / Douglas, Alexander D / de Jongh, Willem A / Smith, Robert / Berrie, Eleanor / Noe, Amy R / Diggs, Carter L / Soisson, Lorraine A / Ashfield, Rebecca / Faust, Saul N / Goodman, Anna L / Lawrie, Alison M / Nugent, Fay L / Alter, Galit / Long, Carole A / Draper, Simon J

Med (New York, N.Y.)

2021 Volume 2, Issue 6, Page(s) 701–719.e19

Abstract: Background: Development of an effective vaccine against the pathogenic blood-stage infection of human malaria has proved challenging, and no candidate vaccine has affected blood-stage parasitemia following controlled human malaria infection (CHMI) with ... ...

Abstract	Background: Development of an effective vaccine against the pathogenic blood-stage infection of human malaria has proved challenging, and no candidate vaccine has affected blood-stage parasitemia following controlled human malaria infection (CHMI) with blood-stage Methods: We undertook a phase I/IIa clinical trial in healthy adults in the United Kingdom of the RH5.1 recombinant protein vaccine, targeting the Findings: The RH5.1/AS01 Conclusions: Our data provide a new framework to guide rational design and delivery of next-generation vaccines to protect against malaria disease. Funding: This study was supported by USAID, UK MRC, Wellcome Trust, NIAID, and the NIHR Oxford-BRC.
MeSH term(s)	Adult ; Humans ; Malaria/chemically induced ; Malaria Vaccines/therapeutic use ; Malaria, Falciparum/prevention & control ; Plasmodium falciparum ; Vaccination ; Vaccines, Synthetic
Chemical Substances	Malaria Vaccines ; Vaccines, Synthetic
Language	English
Publishing date	2021-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2021.03.014
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Article ; Online: Expansion of Treatment for Hepatitis C Virus Infection by Task Shifting to Community-Based Nonspecialist Providers: A Nonrandomized Clinical Trial.

Kattakuzhy, Sarah / Gross, Chloe / Emmanuel, Benjamin / Teferi, Gebeyehu / Jenkins, Veronica / Silk, Rachel / Akoth, Elizabeth / Thomas, Aurielle / Ahmed, Charisse / Espinosa, Michelle / Price, Angie / Rosenthal, Elana / Tang, Lydia / Wilson, Eleanor / Bentzen, Soren / Masur, Henry / Kottilil, Shyam

Annals of internal medicine

2017 Volume 167, Issue 5, Page(s) 311–318

Abstract: Background: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has resulted in high rates of disease cure; however, not enough specialists currently are available to provide care.: Objective: To determine the efficacy of HCV ... ...

Abstract	Background: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has resulted in high rates of disease cure; however, not enough specialists currently are available to provide care. Objective: To determine the efficacy of HCV treatment independently provided by nurse practitioners (NPs), primary care physicians (PCPs), or specialist physicians using DAA therapy. Design: Nonrandomized, open-label clinical trial initiated in 2015. (ClinicalTrials.gov: NCT02339038). Setting: 13 urban, federally qualified health centers (FQHCs) in the District of Columbia. Patients: A referred sample of 600 patients, of whom 96% were black, 69% were male, 82% were treatment naive, and 20% had cirrhosis. Seventy-two percent of the patients had HCV genotype 1a infection. The baseline characteristics of patients seen by each provider type were similar. Intervention: Patients were assigned in a nonrandomized but specified manner to receive treatment from 1 of 5 NPs, 5 PCPs, or 6 specialists. All providers underwent an identical 3-hour training session based on guidelines. Patients received treatment with ledipasvir-sofosbuvir, which was provided on site, according to U.S. Food and Drug Administration labeling requirements. Measurements: Sustained virologic response (SVR). Results: 516 patients achieved SVR, a response rate of 86% (95% CI, 83.0% to 88.7%), with no major safety signals. Response rates were consistent across the 3 provider types: NPs, 89.3% (CI, 83.3% to 93.8%); PCPs, 86.9% (CI, 80.6% to 91.7%); and specialists, 83.8% (CI, 79.0% to 87.8%). Patient loss to follow-up was the major cause of non-SVR. Limitation: Nonrandomized patient distribution; possible referral bias. Conclusion: In a real-world cohort of patients at urban FQHCs, HCV treatment administered by nonspecialist providers was as safe and effective as that provided by specialists. Nurse practitioners and PCPs with compact didactic training could substantially expand the availability of community-based providers to escalate HCV therapy, bridging existing gaps in the continuum of care for patients with HCV infection. Primary funding source: National Institutes of Health and Gilead Sciences.
MeSH term(s)	Antiviral Agents/adverse effects ; Antiviral Agents/therapeutic use ; Community Health Services/methods ; Community Health Services/organization & administration ; Community Health Services/standards ; District of Columbia ; Female ; Gastroenterologists ; HIV Infections/complications ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Humans ; Infectious Disease Medicine ; Liver Cirrhosis/complications ; Male ; Medication Adherence ; Middle Aged ; Nurse Practitioners ; Physicians, Primary Care ; Prospective Studies ; Treatment Outcome
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2017-08-08
Publishing country	United States
Document type	Clinical Trial, Phase IV ; Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M17-0118
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Article ; Online: Production, quality control, stability, and potency of cGMP-produced

Jin, Jing / Tarrant, Richard D / Bolam, Emma J / Angell-Manning, Philip / Soegaard, Max / Pattinson, David J / Dulal, Pawan / Silk, Sarah E / Marshall, Jennifer M / Dabbs, Rebecca A / Nugent, Fay L / Barrett, Jordan R / Hjerrild, Kathryn A / Poulsen, Lars / Jørgensen, Thomas / Brenner, Tanja / Baleanu, Ioana N / Parracho, Helena M / Tahiri-Alaoui, Abdessamad /

Whale, Gary / Moyle, Sarah / Payne, Ruth O / Minassian, Angela M / Higgins, Matthew K / Detmers, Frank J / Lawrie, Alison M / Douglas, Alexander D / Smith, Robert / de Jongh, Willem A / Berrie, Eleanor / Ashfield, Rebecca / Draper, Simon J

NPJ vaccines

2018 Volume 3, Page(s) 32

Abstract: Plasmodium ... ...

Abstract	Plasmodium falciparum
Language	English
Publishing date	2018-08-17
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-018-0071-7
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Article ; Online: T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial.

Nature medicine

2020 Volume 27, Issue 2, Page(s) 270–278

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed
MeSH term(s)	Adolescent ; Antibody Formation/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/immunology ; COVID-19/virology ; COVID-19 Vaccines/immunology ; ChAdOx1 nCoV-19 ; Dose-Response Relationship, Immunologic ; Female ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Immunoglobulin A/immunology ; Immunoglobulin M/immunology ; Interferon-gamma/metabolism ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; Protein Subunits/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; T-Lymphocytes/immunology ; Vaccination ; Young Adult
Chemical Substances	COVID-19 Vaccines ; Immunoglobulin A ; Immunoglobulin M ; Protein Subunits ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Interferon-gamma (82115-62-6) ; ChAdOx1 nCoV-19 (B5S3K2V0G8)
Language	English
Publishing date	2020-12-17
Publishing country	United States
Document type	Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-020-01194-5
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Article ; Online: Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2016 Volume 62, Issue 4, Page(s) 440–447

Abstract: Background: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third ... ...

Abstract	Background: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis. Methods: Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged ≥18 years, had chronic HCV genotype 1 infection (serum HCV RNA ≥2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay. Results: Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P = .51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen. Conclusions: Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy. Chinese clinical trials registration: CT01805882.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/therapeutic use ; Benzimidazoles/administration & dosage ; Cohort Studies ; Drug Therapy, Combination/methods ; Female ; Fluorenes/administration & dosage ; Genotype ; Hepacivirus/classification ; Hepacivirus/genetics ; Hepacivirus/isolation & purification ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/pathology ; Hepatitis C, Chronic/virology ; Humans ; Liver Cirrhosis/pathology ; Male ; Middle Aged ; Quinolines/administration & dosage ; Sofosbuvir/administration & dosage ; Treatment Outcome ; Young Adult
Chemical Substances	Antiviral Agents ; Benzimidazoles ; Fluorenes ; GS-9451 ; Quinolines ; ledipasvir (013TE6E4WV) ; Sofosbuvir (WJ6CA3ZU8B)
Language	English
Publishing date	2016-02-15
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/civ897
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