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https://www.readbyqxmd.com/read/28434376/pre-clinical-and-clinical-development-of-the-first-placental-malaria-vaccine
#1
Caroline Pehrson, Ali Salanti, Thor G Theander, Morten A Nielsen
Malaria during pregnancy is a massive health problem in endemic areas. Placental malaria infections caused by Plasmodium falciparum are responsible for up to one million babies being born with a low birth weight every year. Significant efforts have been invested into preventing the condition. Areas covered: Pub Med was searched using the broad terms "malaria parasite placenta" to identify studies of interactions between parasite and host, "prevention of placental malaria" to identify current strategies to prevent placental malaria, and "placental malaria vaccine" to identify pre-clinical vaccine development...
April 24, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28408175/an-oncofetal-glycosaminoglycan-modification-provides-therapeutic-access-to-cisplatin-resistant-bladder-cancer
#2
Roland Seiler, Htoo Zarni Oo, Davide Tortora, Thomas M Clausen, Chris K Wang, Gunjan Kumar, Marina Ayres Pereira, Maj S Ørum-Madsen, Mette Ø Agerbæk, Tobias Gustavsson, Mie A Nordmaj, Jamie R Rich, Nada Lallous, Ladan Fazli, Sherry S Lee, James Douglas, Tilman Todenhöfer, Shaghayegh Esfandnia, Dulguun Battsogt, John S Babcook, Nader Al-Nakouzi, Simon J Crabb, Igor Moskalev, Bernhard Kiss, Elai Davicioni, George N Thalmann, Paul S Rennie, Peter C Black, Ali Salanti, Mads Daugaard
BACKGROUND: Although cisplatin-based neoadjuvant chemotherapy (NAC) improves survival of unselected patients with muscle-invasive bladder cancer (MIBC), only a minority responds to therapy and chemoresistance remains a major challenge in this disease setting. OBJECTIVE: To investigate the clinical significance of oncofetal chondroitin sulfate (ofCS) glycosaminoglycan chains in cisplatin-resistant MIBC and to evaluate these as targets for second-line therapy. DESIGN, SETTING, AND PARTICIPANTS: An ofCS-binding recombinant VAR2CSA protein derived from the malaria parasite Plasmodium falciparum (rVAR2) was used as an in situ, in vitro, and in vivo ofCS-targeting reagent in cisplatin-resistant MIBC...
April 10, 2017: European Urology
https://www.readbyqxmd.com/read/28292298/erratum-to-characteristics-and-knowledge-synthesis-approach-for-456-network-meta-analyses-a-scoping-review
#3
Wasifa Zarin, Areti Angeliki Veroniki, Vera Nincic, Afshin Vafaei, Emily Reynen, Sanober S Motiwala, Jesmin Antony, Shannon M Sullivan, Patricia Rios, Caitlin Daly, Joycelyne Ewusie, Maria Petropoulou, Adriani Nikolakopoulou, Anna Chaimani, Georgia Salanti, Sharon E Straus, Andrea C Tricco
No abstract text is available yet for this article.
March 14, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28131394/novel-adenovirus-encoded-virus-like-particles-displaying-the-placental-malaria-associated-var2csa-antigen
#4
Anne-Marie C Andersson, Mafalda Resende, Ali Salanti, Morten A Nielsen, Peter J Holst
The malaria parasite Plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. The VAR2CSA mediated binding to a distinct chondroitin sulphate A (CSA) is a crucial step in the pathophysiology of placental malaria and the CSA binding region of VAR2CSA has been identified as a promising vaccine target against placental malaria. Here we designed adenovirus encoded virus-like particles (VLP) by co-encoding Simian Immunodeficiency Virus (SIV) gag and VAR2CSA...
January 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28088593/additional-considerations-are-required-when-preparing-a-protocol-for-a-systematic-review-with-multiple-interventions
#5
Anna Chaimani, Deborah M Caldwell, Tianjing Li, Julian P T Higgins, Georgia Salanti
OBJECTIVES: The number of systematic reviews that aim to compare multiple interventions using network meta-analysis is increasing. In this study, we highlight aspects of a standard systematic review protocol that may need modification when multiple interventions are to be compared. STUDY DESIGN AND SETTING: We take the protocol format suggested by Cochrane for a standard systematic review as our reference and compare the considerations for a pairwise review with those required for a valid comparison of multiple interventions...
January 11, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28052774/characteristics-and-knowledge-synthesis-approach-for-456-network-meta-analyses-a-scoping-review
#6
Wasifa Zarin, Areti Angeliki Veroniki, Vera Nincic, Afshin Vafaei, Emily Reynen, Sanober S Motiwala, Jesmin Antony, Shannon M Sullivan, Patricia Rios, Caitlin Daly, Joycelyne Ewusie, Maria Petropoulou, Adriani Nikolakopoulou, Anna Chaimani, Georgia Salanti, Sharon E Straus, Andrea C Tricco
BACKGROUND: Network meta-analysis (NMA) has become a popular method to compare more than two treatments. This scoping review aimed to explore the characteristics and methodological quality of knowledge synthesis approaches underlying the NMA process. We also aimed to assess the statistical methods applied using the Analysis subdomain of the ISPOR checklist. METHODS: Comprehensive literature searches were conducted in MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews from inception until April 14, 2015...
January 5, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28012775/comparison-of-functional-assays-used-in-the-clinical-development-of-a-placental-malaria-vaccine
#7
Caroline Pehrson, Kristine K Heno, Yvonne Adams, Mafalda Resende, Line Mathiesen, Max Soegaard, Willem A de Jongh, Thor G Theander, Ali Salanti, Morten A Nielsen
BACKGROUND: Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria are in clinical development. The purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines...
December 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27997697/burkitt-lymphoma-expresses-oncofetal-chondroitin-sulfate-without-being-a-reservoir-for-placental-malaria-sequestration
#8
Mette Ø Agerbaek, Marina A Pereira, Thomas M Clausen, Caroline Pehrson, Htoo Zarni Oo, Charlotte Spliid, Jamie R Rich, Vincent Fung, Francis Nkrumah, Janet Neequaye, Robert J Biggar, Steven J Reynolds, Giovanna Tosato, Sheeja T Pullarkat, Leona W Ayers, Thor G Theander, Mads Daugaard, Kishor Bhatia, Morten A Nielsen, Sam M Mbulaiteye, Ali Salanti
Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. ofCS is absent in other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines...
April 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27917593/%C3%AE-markov-model-for-longitudinal-studies-with-incomplete-dichotomous-outcomes
#9
Orestis Efthimiou, Nicky Welton, Myrto Samara, Stefan Leucht, Georgia Salanti
Missing outcome data constitute a serious threat to the validity and precision of inferences from randomized controlled trials. In this paper, we propose the use of a multistate Markov model for the analysis of incomplete individual patient data for a dichotomous outcome reported over a period of time. The model accounts for patients dropping out of the study and also for patients relapsing. The time of each observation is accounted for, and the model allows the estimation of time-dependent relative treatment effects...
March 2017: Pharmaceutical Statistics
https://www.readbyqxmd.com/read/27900573/erratum-to-molecular-dissection-of-placental-malaria-protein-var2csa-interaction-with-a-chemo-enzymatically-synthesized-chondroitin-sulfate-library
#10
Nobuo Sugiura, Thomas Mandel Clausen, Tatsumasa Shioiri, Tobias Gustavsson, Hideto Watanabe, Ali Salanti
No abstract text is available yet for this article.
December 2016: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27864068/bibliographic-study-showed-improving-statistical-methodology-of-network-meta-analyses-published-between-1999-and-2015
#11
REVIEW
Maria Petropoulou, Adriani Nikolakopoulou, Areti-Angeliki Veroniki, Patricia Rios, Afshin Vafaei, Wasifa Zarin, Myrsini Giannatsi, Shannon Sullivan, Andrea C Tricco, Anna Chaimani, Matthias Egger, Georgia Salanti
OBJECTIVES: To assess the characteristics and core statistical methodology specific to network meta-analyses (NMAs) in clinical research articles. STUDY DESIGN AND SETTING: We searched MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from inception until April 14, 2015, for NMAs of randomized controlled trials including at least four different interventions. Two reviewers independently screened potential studies, whereas data abstraction was performed by a single reviewer and verified by a second...
February 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/27825348/bacterial-superglue-generates-a-full-length-circumsporozoite-protein-virus-like-particle-vaccine-capable-of-inducing-high-and-durable-antibody-responses
#12
Christoph M Janitzek, Sungwa Matondo, Susan Thrane, Morten A Nielsen, Reginald Kavishe, Steve B Mwakalinga, Thor G Theander, Ali Salanti, Adam F Sander
BACKGROUND: Malaria, caused by Plasmodium falciparum, continues to have a devastating impact on global health, emphasizing the great need for a malaria vaccine. The circumsporozoite protein (CSP) is an attractive target for a malaria vaccine, and forms a major component of RTS,S, the most clinically advanced malaria vaccine. The clinical efficacy of RTS,S has been moderate, yet has demonstrated the viability of a CSP-based malaria vaccine. In this study, a vaccine comprised of the full-length CSP antigen presented on a virus-like particle (VLP) is produced using a split-intein conjugation system (SpyTag/SpyCatcher) and the immunogenicity is tested in mice...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27814765/antibody-responses-to-the-full-length-var2csa-and-its-dbl-domains-in-cameroonian-children-and-teenagers
#13
Barriere A Y Fodjo, Njika Atemnkeng, Livo Esemu, Emile K Yuosembom, Isabella A Quakyi, Viviane H M Tchinda, Joseph Smith, Ali Salanti, Jude Bigoga, Diane W Taylor, Rose G F Leke, Anna Babakhanyan
BACKGROUND: Antigenic variation of Plasmodium falciparum erythrocyte membrane protein 1 is a key parasite mechanism for immune evasion and parasite survival. It is assumed that the number of parasites expressing the same var gene must reach high enough numbers before the host can produce detectable levels of antibodies (Ab) to the variant. VAR2CSA is a protein coded for by one of 60 var genes that is expressed on the surface of infected erythrocytes (IE) and mediates IE binding to the placenta...
November 4, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27726982/placebo-response-rates-in-antidepressant-trials-a-systematic-review-of-published-and-unpublished-double-blind-randomised-controlled-studies
#14
Toshi A Furukawa, Andrea Cipriani, Lauren Z Atkinson, Stefan Leucht, Yusuke Ogawa, Nozomi Takeshima, Yu Hayasaka, Anna Chaimani, Georgia Salanti
BACKGROUND: Previous studies have shown that placebo response rates in antidepressant trials have been increasing since the 1970s. However, these studies have been based on outdated or limited datasets and have used inappropriate statistical methods. We did a systematic review of placebo-controlled randomised controlled trials of antidepressants to examine associations between placebo-response rates and study and patient characteristics. METHODS: In this systematic review, we searched for published and unpublished double-blind randomised placebo-controlled trials of first-generation and second-generation antidepressants for acute treatment of major depression in adults (update: Jan 8, 2016)...
November 2016: Lancet Psychiatry
https://www.readbyqxmd.com/read/27587588/continuously-updated-network-meta-analysis-and-statistical-monitoring-for-timely-decision-making
#15
Adriani Nikolakopoulou, Dimitris Mavridis, Matthias Egger, Georgia Salanti
Pairwise and network meta-analysis (NMA) are traditionally used retrospectively to assess existing evidence. However, the current evidence often undergoes several updates as new studies become available. In each update recommendations about the conclusiveness of the evidence and the need of future studies need to be made. In the context of prospective meta-analysis future studies are planned as part of the accumulation of the evidence. In this setting, multiple testing issues need to be taken into account when the meta-analysis results are interpreted...
September 1, 2016: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/27556547/placental-sequestration-of-plasmodium-falciparum-malaria-parasites-is-mediated-by-the-interaction-between-var2csa-and-chondroitin-sulfate-a-on-syndecan-1
#16
Marina Ayres Pereira, Thomas Mandel Clausen, Caroline Pehrson, Yang Mao, Mafalda Resende, Mads Daugaard, Anders Riis Kristensen, Charlotte Spliid, Line Mathiesen, Lisbeth E Knudsen, Peter Damm, Thor G Theander, Stefan R Hansson, Morten A Nielsen, Ali Salanti
During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27487843/an-overview-of-methods-for-network-meta-analysis-using-individual-participant-data-when-do-benefits-arise
#17
Thomas Pa Debray, Ewoud Schuit, Orestis Efthimiou, Johannes B Reitsma, John Pa Ioannidis, Georgia Salanti, Karel Gm Moons
Network meta-analysis (NMA) is a common approach to summarizing relative treatment effects from randomized trials with different treatment comparisons. Most NMAs are based on published aggregate data (AD) and have limited possibilities for investigating the extent of network consistency and between-study heterogeneity. Given that individual participant data (IPD) are considered the gold standard in evidence synthesis, we explored statistical methods for IPD-NMA and investigated their potential advantages and limitations, compared with AD-NMA...
August 2, 2016: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/27441183/real-time-and-label-free-determination-of-ligand-binding-kinetics-to-primary-cancer-tissue-specimens-a-novel-tool-for-the-assessment-of-biomarker-targeting
#18
Thomas Mandel Clausen, Marina Ayres Pereira, Htoo Zarni Oo, Mafalda Resende, Tobias Gustavson, Yang Mao, Nobuo Sugiura, Janet Liew, Ladan Fazli, Thor G Theander, Mads Daugaard, Ali Salanti
In clinical oncology, diagnosis and evaluation of optimal treatment strategies are mostly based on histopathological examination combined with immunohistochemical (IHC) expression analysis of cancer-associated antigens in formalin fixed paraffin-embedded (FFPE) tissue biopsies. However, informative IHC analysis depends on both the specificity and affinity of the binding reagent, which are inherently difficult to quantify in situ. Here we describe a label-free method that allows for the direct and real-time assessment of molecular binding kinetics in situ on FFPE tissue specimens using quartz crystal microbalance (QCM) enabled biosensor technology...
July 2016: Sensing and Bio-Sensing Research
https://www.readbyqxmd.com/read/27435721/network-meta-analyses-should-be-the-highest-level-of-evidence-in-treatment-guidelines
#19
EDITORIAL
Stefan Leucht, Anna Chaimani, Andrea S Cipriani, John M Davis, Toshi A Furukawa, Georgia Salanti
No abstract text is available yet for this article.
September 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/27401359/comparative-efficacy-and-acceptability-of-first-generation-and-second-generation-antidepressants-in-the-acute-treatment-of-major-depression-protocol-for-a-network-meta-analysis
#20
Toshi A Furukawa, Georgia Salanti, Lauren Z Atkinson, Stefan Leucht, Henricus G Ruhe, Erick H Turner, Anna Chaimani, Yusuke Ogawa, Nozomi Takeshima, Yu Hayasaka, Hissei Imai, Kiyomi Shinohara, Aya Suganuma, Norio Watanabe, Sarah Stockton, John R Geddes, Andrea Cipriani
INTRODUCTION: Many antidepressants are indicated for the treatment of major depression. Two network meta-analyses have provided the most comprehensive assessments to date, accounting for both direct and indirect comparisons; however, these reported conflicting interpretation of results. Here, we present a protocol for a systematic review and network meta-analysis aimed at updating the evidence base and comparing all second-generation as well as selected first-generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression...
July 8, 2016: BMJ Open
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